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Generate exact multiple choice questions as give below 1. **Which round of negotiations led to the establishment of the World Trade Organization (WTO)?** - (a) Doha Round - (b) Tokyo Round - (c) Uruguay Round - (d) Kennedy Round **Answer:** (c) Uruguay Round 2. **The General Agreement on Tariffs and Trade (GATT) dealt with:** - (a) Goods only - (b) Services only - (c) Intellectual property only - (d) All of the above **Answer:** (a) Goods only 3. **The 'National Treatment' principle means:** - (a) Exported products are treated equally in the domestic market - (b) Imported goods are treated the same as local goods in the domestic market - (c) Exported products should have the same tariff - (d) None of the above **Answer:** (b) Imported goods are treated the same as local goods in the domestic market 4. **'Bound tariff' refers to:** - (a) A limit on tariffs for imports based on WTO commitments - (b) The tax rate on all exports - (c) The overall cost of tariffs - (d) A tariff-free trade condition **Answer:** (a) A limit on tariffs for imports based on WTO commitments 5. **The Most-Favoured Nation (MFN) principle ensures:** - (a) Equal treatment for all WTO members - (b) Only certain countries receive benefits - (c) Tariffs are raised annually - (d) One country is favored over others **Answer:** (a) Equal treatment for all WTO members 6. **The Agreement on Agriculture includes commitments in:** - (a) Market access, domestic support, and export subsidies - (b) Increasing crop yield and technology access - (c) Subsidizing imports only - (d) Agricultural tariffs only **Answer:** (a) Market access, domestic support, and export subsidies 7. **Which agreement replaced the Multi-Fiber Arrangement (MFA)?** - (a) Agreement on Textiles and Clothing - (b) Agreement on Agriculture - (c) TRIPS Agreement - (d) Technical Barriers to Trade Agreement **Answer:** (a) Agreement on Textiles and Clothing 8. **The WTO's TRIPS Agreement pertains to:** - (a) Agricultural products - (b) Intellectual property rights - (c) Investment measures - (d) Customs valuation **Answer:** (b) Intellectual property rights 9. **The Doha Round primarily focuses on:** - (a) Tariffs on manufactured goods - (b) Trade in agricultural goods - (c) Technology trade - (d) Intellectual property in medicine **Answer:** (b) Trade in agricultural goods 10. **The WTO aims to:** - (a) Restrict all trade - (b) Facilitate free and fair trade - (c) Promote monopoly - (d) Limit member negotiations **Answer:** (b) Facilitate free and fair trade 11. **RTAs aim to:** - (a) Block international trade - (b) Reduce trade barriers within a group of countries - (c) Increase tariffs among members - (d) Promote non-trade-related policies **Answer:** (b) Reduce trade barriers within a group of countries 12. **Customs unions require members to:** - (a) Keep individual external tariffs - (b) Impose the same external tariff on non-members - (c) Remove tariffs only temporarily - (d) Avoid any tariffs within the union **Answer:** (b) Impose the same external tariff on non-members 13. **The WTO's highest decision-making body is:** - (a) General Council - (b) Ministerial Conference - (c) TRIPS Council - (d) Dispute Settlement Body **Answer:** (b) Ministerial Conference 14. **Which principle prevents discrimination between WTO members?** - (a) MFN - (b) National Treatment - (c) Market Access - (d) Subsidy Reduction **Answer:** (a) MFN 15. **A common market involves:** - (a) A shared currency - (b) Free movement of goods, services, and factors of production - (c) Only trade agreements for goods - (d) No tariffs on agriculture **Answer:** (b) Free movement of goods, services, and factors of production 16. **The Agreement on Subsidies and Countervailing Measures addresses:** - (a) Trade in textiles - (b) Subsidies that distort trade - (c) All intellectual property laws - (d) Agricultural trade only **Answer:** (b) Subsidies that distort trade 17. **The WTO's TRIMs Agreement regulates:** - (a) Investments - (b) Trade in goods - (c) Trade in services - (d) Agricultural products **Answer:** (a) Investments 18. **The primary goal of the WTO's SPS Agreement is:** - (a) To allow subsidies on food exports - (b) To prevent arbitrary sanitary restrictions on trade - (c) To regulate intellectual property - (d) To impose environmental standards **Answer:** (b) To prevent arbitrary sanitary restrictions on trade 19. **A trading bloc is:** - (a) A group of countries with no trade agreements - (b) A group of countries that may have a common external tariff - (c) Only formed by countries from the same continent - (d) An agreement that restricts all trade **Answer:** (b) A group of countries that may have a common external tariff 20. **The GATT was succeeded by the WTO because:** - (a) GATT was only for developed countries - (b) WTO covers more areas like services and intellectual property - (c) GATT was non-binding - (d) WTO allows subsidies for agriculture **Answer:** (b) WTO covers more areas like services and intellectual property Certainly! Here are an additional 30 multiple-choice questions based on the document content, with answers provided after each question. --- ### Additional Questions and Answers 21. **The WTO’s Agreement on Technical Barriers to Trade (TBT) seeks to:** - (a) Restrict imports to a minimum - (b) Prevent standards from becoming unnecessary trade barriers - (c) Allow countries to set any standard for goods - (d) Promote only national standards for products **Answer:** (b) Prevent standards from becoming unnecessary trade barriers 22. **The Trade Policy Review Mechanism (TPRM) is designed to:** - (a) Impose tariffs on certain goods - (b) Regularly review and assess national trade policies - (c) Regulate customs duties globally - (d) Control intellectual property rights **Answer:** (b) Regularly review and assess national trade policies 23. **The principle of “progressive liberalization” means that:** - (a) Trade barriers are reduced gradually over time - (b) All tariffs are removed immediately - (c) Only developed countries reduce trade barriers - (d) No commitments are required from developing countries **Answer:** (a) Trade barriers are reduced gradually over time 24. **Which council oversees the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS)?** - (a) General Council - (b) Services Council - (c) TRIPS Council - (d) Agriculture Council **Answer:** (c) TRIPS Council 25. **The WTO’s 'Dispute Settlement Body' is responsible for:** - (a) Deciding on national trade policies - (b) Settling trade disputes between member countries - (c) Creating new trade agreements - (d) Setting tariffs for member countries **Answer:** (b) Settling trade disputes between member countries 26. **A customs union differs from a free trade area because it:** - (a) Allows tariffs between member countries - (b) Establishes a common external tariff for non-members - (c) Applies only to services - (d) Imposes import quotas on all goods **Answer:** (b) Establishes a common external tariff for non-members 27. **Which of the following agreements deals with cross-border investments?** - (a) TRIPS - (b) TBT - (c) TRIMs - (d) GATS **Answer:** (c) TRIMs 28. **In a preferential trade agreement, member countries:** - (a) Impose the same tariffs as non-members - (b) Reduce trade barriers for each other only - (c) Apply high tariffs to non-member countries - (d) Have no external trade barriers **Answer:** (b) Reduce trade barriers for each other only 29. **The WTO’s Agreement on Agriculture includes which commitment?** - (a) Export subsidies for all agricultural goods - (b) Reduction of domestic support for farmers - (c) Complete elimination of tariffs on food products - (d) Increase in import quotas on agricultural goods **Answer:** (b) Reduction of domestic support for farmers 30. **The Agreement on Anti-Dumping allows countries to:** - (a) Increase exports by lowering prices - (b) Impose duties on imports sold below fair market value - (c) Eliminate all tariffs on certain goods - (d) Restrict domestic production of certain goods **Answer:** (b) Impose duties on imports sold below fair market value 31. **The main objective of WTO’s “National Treatment” principle is to:** - (a) Prevent imports altogether - (b) Treat foreign goods the same as domestic goods - (c) Impose tariffs on all foreign products - (d) Promote exports **Answer:** (b) Treat foreign goods the same as domestic goods 32. **Which of the following is a major goal of the WTO?** - (a) Ensuring trade restrictions remain high - (b) Promoting international free trade and competition - (c) Limiting access to global markets - (d) Supporting only developed countries **Answer:** (b) Promoting international free trade and competition 33. **An economic and monetary union involves:** - (a) A free trade area only - (b) A common currency among members - (c) No external trade agreements - (d) Different currencies for each member country **Answer:** (b) A common currency among members 34. **The WTO's Ministerial Conference meets:** - (a) Annually - (b) Every two years - (c) Quarterly - (d) Every five years **Answer:** (b) Every two years 35. **The WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) mandates:** - (a) Free trade for all countries - (b) Uniform intellectual property protection standards - (c) Different IP laws for each country - (d) No IP protection for developing countries **Answer:** (b) Uniform intellectual property protection standards 36. **The WTO principle of 'transparency' requires member countries to:** - (a) Keep trade policies secret - (b) Publicly disclose trade policies and practices - (c) Have identical trade policies - (d) Eliminate tariffs on all goods **Answer:** (b) Publicly disclose trade policies and practices 37. **One of the WTO's objectives in dispute settlement is to:** - (a) Resolve trade disputes peacefully - (b) Impose sanctions on non-members - (c) Regulate global tariffs - (d) Control member states' import quotas **Answer:** (a) Resolve trade disputes peacefully 38. **Under the WTO's Market Access commitment, member countries agree to:** - (a) Allow unrestricted imports - (b) Set maximum tariff levels on imported goods - (c) Ban certain goods from other countries - (d) Only trade with specific countries **Answer:** (b) Set maximum tariff levels on imported goods 39. **GATS, or the General Agreement on Trade in Services, governs trade in:** - (a) Agricultural goods - (b) Intellectual property - (c) Services - (d) Manufactured products **Answer:** (c) Services 40. **The Agreement on Pre-shipment Inspection (PSI) aims to:** - (a) Ensure high tariffs on all imports - (b) Allow for inspection of goods before shipping - (c) Eliminate export taxes - (d) Control intellectual property trade **Answer:** (b) Allow for inspection of goods before shipping 41. **Which of the following agreements aims to harmonize customs valuation?** - (a) Anti-Dumping Agreement - (b) Customs Valuation Agreement - (c) TRIMs Agreement - (d) Agreement on Subsidies **Answer:** (b) Customs Valuation Agreement 42. **A significant aspect of the Doha Round is:** - (a) Reducing tariffs on agricultural products - (b) Restricting intellectual property rights - (c) Eliminating all forms of trade - (d) Blocking services trade agreements **Answer:** (a) Reducing tariffs on agricultural products 43. **The term “dumping” in international trade refers to:** - (a) Exporting goods at prices lower than domestic market prices - (b) Importing goods illegally - (c) Increasing domestic prices - (d) Imposing excessive tariffs **Answer:** (a) Exporting goods at prices lower than domestic market prices 44. **WTO members are expected to follow which key principle in reducing tariffs?** - (a) National Treatment - (b) Progressive Liberalization - (c) Quota System - (d) Non-Discrimination **Answer:** (b) Progressive Liberalization 45. **The WTO aims to promote fair competition by:** - (a) Allowing tariffs as the only form of protection - (b) Supporting MFN and anti-dumping measures - (c) Limiting access to agricultural products - (d) Increasing subsidies **Answer:** (b) Supporting MFN and anti-dumping measures 46. **A plurilateral agreement within the WTO:** - (a) Includes all WTO members - (b) Involves only specific countries with shared interests - (c) Bans all tariffs for members - (d) Imposes global trade restrictions **Answer:** (b) Involves only specific countries with shared interests 47. **Trade facilitation in the WTO context means:** - (a) Making trade faster, cheaper, and more predictable - (b) Increasing tariffs on imports - (c) Eliminating all customs procedures - (d) Restricting trade with non-members **Answer:** (a) Making trade faster, cheaperGUIDELINES ON THE ESTABLISHMENT AND IMPLEMENTATION OF THE RESULTS-BASED PERFORMANCE MANAGEMENT SYSTEM IN THE DEPARTMENT OF EDUCATION I. Rationale 1. The Civil Service Commission (CSC), through the issuance of Memorandum Circular (MC) No. 06, series of 2012, sets the guidelines on the establishment and implementation of the Strategic Performance Management System (SPMS) in all government agencies. The SPMS gives emphasis to the strategic alignment of the agency’s thrusts with the day-to-day operation of the units and individual personnel within the organization. It focuses on measures of performance vis-a-vis the targeted milestones, and provides a credible and verifiable basis for assessing the organizational outcomes and the collective performance of the government employees. 2. As a learner-centered institution, the Department of Education (DepEd) is committed to continuously improve itself to better serve the Filipino learners and the community. The adoption of the SPMS in DepEd strengthens the culture of performance and accountability in the agency, with the DepEd’s mandate, vision and mission at its core. 3. There is a need to concretize the linkage between the organizational thrusts and the performance management system. It is important to ensure organizational effectiveness and track individual improvement and efficiency by cascading the institutional accountabilities to the various levels, units and individual personnel, as anchored on the establishment of a rational and factual basis for performance targets and measures. Finally, it is necessary to link the SPMS with other systems relating to human resources and to ensure adherence to the principle of performance-based tenure and incentives. 4. In view of the above, this Order aims to adopt the SPMS as the Results-based Performance Management System (RPMS). II. Scope of Policy 5. This DepEd Order provides for the establishment and implementation of the RPMS in all DepEd schools and offices, covering all officials and employees, school-based and non school-based, in the Department holding regular plantilla positions. It stipulates the specific mechanisms, criteria and processes for the performance target setting, monitoring, evaluation and development planning. IV. Policy Statement 9. The DepEd hereby sets the guidelines on the establishment and implementation of the Results-based Performance Management System (RPMS) in the Department, stipulating the strategies, methods, tools and rewards for assessing the accomplishments vis-a-vis the commitments. This will be used for measuring and rewarding higher levels of performance of the various units and development planning of all personnel in all levels. 10. For non school-based personnel, the RPMS shall provide for an objective and verifiable basis for rating and ranking the performance of units and individual personnel in view of the granting of the Performance-Based Bonus (PBB) starting 2015. 11. For school-based personnel, the RPMS shall be used only as an appraisal tool, which shall be the basis for training and development. The granting of PBB shall be governed by the existing PBB guidelines. 12. The Department shall adopt the RPMS framework shown in Annex B. 13. The DepEd RPMS shall follow the four-stage performance management system cycle as prescribed by the CSC: i. Performance planning and commitment (Phase I); ii. Performance monitoring and coaching (Phase II); iii. Performance review and evaluation (Phase III); and iv. Performance rewarding and development planning (Phase IV). V. Performance Cycle/Process 14. The RPMS shall align the performance targets and accomplishments with the Department’s mandate, vision, mission and strategic goals. It shall ensure 100% results orientation vis-a-vis the planned targets. On the other hand, the ratee’s demonstration of the required competencies shall be monitored for developmental purposes only. 15. The RPMS cycle shall cover performance for one whole year. All school-based personnel shall follow a performance cycle starting in April of the current year and ending in March of the following year; while non school-based personnel shall follow a performance cycle starting in January and ending in December. Annexes C and D illustrate the performance cycles which shall apply to school-based and non school-based personnel, respectively. 16. The performance planning and commitment shall be done prior to the beginning of the performance cycle; while the performance monitoring and coaching shall take place immediately after Phase I, and continue throughout the performance cycle. The performance review and evaluation, as well as the performance rewarding and development planning shall be done at the end of the performance cycle. A. Phase I: Performance Planning and Commitment 17. The performance planning and commitment shall be done prior to the start of the performance cycle where the rater meets with the ratee to discuss and agree on the following: i. Office KRAs, Objectives and Performance Indicators as anchored to the overall organizational outcomes; and ii. Individual KRAs, Objectives and Performance Indicators as anchored to the Office KRAs and Objectives. 18. The Office Performance Commitment and Review Form (OPCRF) shall be accomplished by the head of office to reflect the Office KRAs, Objectives and Performance Indicators. The head of office, in coordination with the Planning Office, shall ensure alignment of the office plans and commitments to the overall organizational outcomes. The OPCRF shall be equivalent to the IPCRF of the head of office. A sample of the filled out OPCRF, including the instructions for accomplishing the form, is shown in Annex E. 19. The Individual Performance Commitment and Review Form (IPCRF) shall be accomplished by the individual personnel to reflect the agreed Individual KRAs, Objectives and Performance Indicators. A sample of the filled out IPCRF, including the instructions for accomplishing the form, is shown in Annex F. 20. Defining the Key Result Areas. The head of office, in coordination with the Planning Office, shall define the office KRAs as anchored on the overall organizational outcomes. The rater and the ratee shall discuss and agree on the break down of the office KRAs into individual KRAs. Three (3) to five (5) KRAs shall be defined for each office and individual employee. KRAs are broad categories of general outputs or outcomes. It is the mandate or function of the office and/or individual employee. The KRA is the reason why an office and/or job exist. It is an area where the office and/or individual employee are expected to focus on. 21. Setting the Objectives. The head of office shall set three (3) objectives per office KRA. The rater and the ratee shall discuss and agree on three (3) objectives per individual KRA. Objectives are specific tasks, which an office and/or employee need to do to achieve their specific KRAs. In objective setting, the SMART criteria, which stands for Specific, Measurable, Attainable, Relevant, Time Bound, shall be applied. The SMART criteria are illustrated in Annex G. 22. Setting the Timeline. The timeline shall define the target date for accomplishing each of the Objectives. The timeline for the office Objectives shall be set by the head of office in coordination with the Planning Office and School Planning Team; while the timeline for the individual Objectives shall be discussed and agreed by the rater and the ratee. 23. Assigning the Weight. Assigning of weights shall be done per KRA. Weights for each office KRA shall be assigned by the head of office in coordination with the Planning Office; while the weights for each of the individual KRAs shall be discussed and agreed upon by the rater and the ratee. 24. Identifying the Performance Indicators. Using a five (5)-point rating scale, the head of office shall identify a performance indicator for each of the office objectives, while the rater and the ratee shall identify and agree on the performance indicator for each of the individual objectives. Performance indicators are exact quantification of objectives expressed through rubrics. They are assessment tools, which gauge whether a performance is positive or negative. In identifying the performance indicator, the operational definition or meaning of each numerical rating shall be indicated under each relevant dimension (i.e., quality, efficiency, or timeliness) per performance target or success indicator. This shall ensure that the rating is objective, impartial and verifiable. Table 1 below discusses the performance measures by which the indicator must satisfy. Table 1. Performance Measures CATEGORY DEFINITION Effectiveness/Quality The extent to which actual performance compares with targeted performance. The degree to which objectives are achieved and the extent to which targeted problems are solved. In management, effectiveness relates to getting the right things done. Efficiency The extent to which time or resources is used for the intended task or purpose. Measures whether targets are accomplished with a minimum amount or quantity of waste, expense, or unnecessary effort. Timeliness Measures whether the deliverable was done on time based on the requirements of the rules and regulations, and/or clients/stakeholders. Time-related performance indicators evaluate such things as project completion deadlines, time management skills and other time-sensitive expectations. Some Performances are only rated on quality and efficiency, some on quality and timeliness, and others on efficiency only. You need not use all three (3) categories. 25. Demonstration of Competencies. During Phase I, the rater shall discuss with the ratee the competencies required of the individual personnel. Competencies are defined as the knowledge, skills and behavior that individuals demonstrate in achieving one’s results. Competencies shall uphold the DepEd’s core values. They represent the way individuals define and live the values. 26. DepEd shall adopt four classes of competencies as follows: i. Core behavioral competencies are competencies, which cut across the organization; ii. Leadership competencies are competencies intended for managerial positions; a. Third level officials b. Chiefs and Assistant Chiefs c. School Heads and Department Heads iii. Staff Core Skills are competencies intended for staff and teaching-related personnel; and iv. Teaching competencies are competencies intended for teachers. The DepEd-required competencies are illustrated in Annex I. 27. The ratee’s demonstration of the required competencies shall be monitored to effectively plan the interventions needed for behavioral and professional development. The assessment in the demonstration of competencies shall not be reflected in the final rating. 28. Reaching Agreement. Once the office and individual KRAs, Objectives and Performance Indicators are clearly defined, the rater and the ratee shall commit and reach an agreement by signing the OPCRF and IPCRF. The signed/approved OPCRF and IPCRF shall be the basis for monitoring and assessment, which shall take place in Phases II and III, respectively. B. Phase II: Performance Monitoring and Coaching 29. The performance monitoring and coaching shall commence after the rater and the ratee commit on the KRAs, Objectives and Performance Indicators, and sign the OPCRF and IPCRF. This shall be done throughout the year. 30. The two (2) main components of Phase II are the following: i. Performance monitoring; and ii. Coaching and feedback. 31. Performance monitoring shall provide key inputs and objective basis for rating. It shall facilitate feedback and provide evidence of performance. Performance monitoring shall be the responsibility of both the rater and the ratee who agree to track and record significant incidents through the use of the Performance Monitoring and Coaching Form (PMCF) shown in Annex J. Significant incidents are actual events and behaviors in which both positive and negative performances are observed and documented. 32. Coaching and feedback shall be a continuous process. Coaching and feedback shall be provided by the rater and/or shall be sought by the ratee to improve work performance and behavior. The rater, as the coach or mentor of the ratee, playing a critical role in the performance monitoring and coaching, shall provide an enabling environment and intervention to improve the office performance and to manage and develop individual potentials. 33. The PMCF shall capture the significant incidents. It shall provide a record of demonstrated behaviors, competencies and performance, and shall be an effective substitute in the absence of quantifiable data. The rater and the ratee shall sign each significant incident recorded in the PMCF to ensure that agreement has been reached. C. Phase III: Performance Review and Evaluation 34. The performance review and evaluation shall be done at the end of the performance cycle to assess the office and individual employee’s performance level based on the commitments and measures as contained in the signed OPCRF and IPCRF. 35. A mid-year review is prescribed to determine the progress in achieving the Objectives. In exceptional cases, and only if the situation warrants, a one-time recalibration of office and individual Objectives shall be allowed during the mid-year review. Exceptional cases shall include instances when high level decisions are taken into effect such as changes in strategic directions, and circumstances beyond the control of the ratee such as natural and/or man-made calamities, including typhoon, earthquake and other fortuitous events. During the mid-year review, the rater shall inform in writing the ratee of the status of performance, in case of an Unsatisfactory or Poor performance. Coaching, feedback and appropriate interventions shall be provided where necessary. 36. The RPMS shall put premium on KRAs towards the realization of organizational vision, mission, strategic priorities and the OPIF logframe. Hence, rating for planned and/or intervening tasks shall always be supported by reports, documents or any output as proofs of actual performance. In the absence of said bases or proofs, a particular task shall not be rated and shall be disregarded. 37. Office and Individual Performance Assessment. The head of office, in coordination with the Planning Office, shall assess the performance of the office vis-a-vis the committed targets at the beginning of the performance cycle. The rater and the ratee shall discuss and agree on the individual assessment based on the actual accomplishments of each of the KRAs and Objectives. The final rating shall be based solely on the accomplishment of the specific objectives as measured by the Performance Indicators. The OPCRF and IPCRF shall be accomplished and completed by the rater and the ratee to: i. Reflect actual accomplishments and results; ii. Rate each of the objectives; iii. Compute for the score per objective; iv. Determine the overall rating for accomplishments; v. Reach an agreement; and vi. Assess the competencies. 38. Initial self-rating shall be encouraged prior to the rater-ratee discussion. 39. Third Level Officials, as heads of offices, shall accomplish the OPCRF for submission to the Planning Office. The individual assessment of Third Level Officials shall be contained in the CESPES Forms for submission to the Career Executive Service Board (CESB). The BHROD and Personnel Division shall be furnished a copy of both forms. 40. Actual Results. The rater and the ratee shall discuss and agree on the actual accomplishments and results based on the performance commitments and measures made at the beginning of the rating period. They shall evaluate each objective whether it has been achieved or not. The significant incidents as reflected in the PMCF shall be considered for the actual results. 41. Rating the Objectives. Based on the actual accomplishments and results, each of the Objectives shall be rated using the rating scale specified below: Table 2. The RPMS Rating Scale NUMERICAL RATING ADJECTIVAL RATING DESCRIPTION OF MEANING OF RATING 5 Outstanding Performance represents an extraordinary level of achievement and commitment in terms of quality and time, technical skills and knowledge, ingenuity, creativity and initiative. Employees at this performance level should have demonstrated exceptional job mastery in all major areas of responsibility. Employee achievement and contributions to the organization are of marked excellence. 4 Very Satisfactory Performance exceeded expectations. All goals, objectives and targets were achieved above the established standards. 3 Satisfactory Performance met expectations in terms of quality of work, efficiency and timeliness. The most critical annual goals were met. 2 Unsatisfactory Performance failed to meet expectations, and/or one or more of the most critical goals were not met. 1 Poor Performance was consistently below expectations, and/or reasonable progress toward critical goals was not made. Significant improvement is needed in one or more important areas. The final assessment shall correspond to the adjectival description of Outstanding, Very Satisfactory, Satisfactory, Unsatisfactory or Poor. The range of adjectival rating is as per attached in Forms A, B, and C. 42. Process for Computing the Score per KRA. i. The rater and ratee shall ensure that each KRA has been assigned weight according to priority. ii. As an option, the rater and ratee may assign weights to objectives which shall be equal to the total weight assigned to a particular KRA. KRA 1 – Weight assigned is 40% Objective 1 is 20% Objective 2 is 10% Objective 3 is 10% iii. The score per KRA shall be computed using the following formula: 43. Plus Factor. The plus factor shall be considered as another KRA. These are value adding accomplishments, which are not covered within the regular duties and responsibilities. The weight on the plus factor shall not exceed the weight of the highest mandated KRA. For teachers, the plus factor shall be limited to work/activities, which contribute to the teaching-learning process. 44. Determining the Overall Rating for Accomplishments. The overall rating/assessment for the accomplishments shall fall within the following adjectival ratings and shall be in three (3) decimal points: Table 3. Adjectival Ratings RANGE ADJECTIVAL RATING 4.500-5.000 Outstanding 3.500-4.499 Very Satisfactory 2.500-3.499 Satisfactory 1.500-2.499 Unsatisfactory below 1.499 Poor 45. Reaching Agreement. Upon determining the overall rating for the actual accomplishments and results, the rater and the ratee shall reach an agreement by signing the OPCRF and IPCRF. The average rating of individual staff members should not go higher than the collective performance assessment of the office. 46. Assessing the Competencies. The rater shall discuss with the ratee the set of competencies observed during the performance cycle. The competencies shall not be reflected in the final rating. Competencies shall be monitored for developmental purposes. In evaluating the individual’s demonstration of competencies, the rating scale in Table 4 shall apply: Table 4. The DepEd Competencies Scale SCALE DEFINITION 5 Role model 4 Consistently demonstrates 3 Most of the time demonstrates 2 Sometimes demonstrates 1 Rarely demonstrates 5 (role model) – all competency indicators 4 (consistently demonstrates) – four competency indicators 3 (most of the time demonstrates) – three competency indicators 2 (sometimes demonstrates) – two competency indicators 1 (rarely demonstrates) – one competency indicator D. Phase IV: Performance Rewarding and Development Planning 47. The results of the performance review and evaluation shall be used in performance rewarding and development planning. This phase shall be done after Phase III. 48. The rater shall discuss and provide qualitative comments, observations and recommendations in the individual employee’s performance commitment, competency assessment and significant incidents which shall be used for training and professional development. These can be written under the strengths and development needs column of the Part IV-Development Plans of the IPCRF. 49. The rater and the ratee shall identify and discuss the individual’s strengths and development needs, and reflect them in the Part IV-Development Plans of the IPCRF. The competencies which the ratee demonstrated consistently and the areas, where the ratee meet or exceed expectations shall be referred to as the ratee’s strengths. The competencies, which the ratee rarely demonstrates and the areas where the ratee has room for improvement and has not met the expectations, shall be identified as the ratee’s development needs. Make a situational SOLO-based questions in the context of school leadership Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. 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BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. 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Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are gover38 Kenji Circulatory System BLOOD CELLS PART 238 DSAT RW Vocab (TD)§38. Идеалдык газ. Казылышуу саны. Орточо эркин жол узундугу.38- النظام السياسي والاداري38課～のは～/～のが～/～のを