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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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Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. 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. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 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. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. 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Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. 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Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, Müller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. 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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 goverEff..rs of ott.-PoFllat i What woLrld hoppen ro our colnrry i, it is ovetsp.pulored? When our counrry is ov€.-populdted, re @ €xp€ri.nce rh€ foll.wirg: Food is our bdsic h@d. Wh€n th€.Cs an ih.re.se ir populdtion it neans thar hore ,@d is iealed. It rheds ho .naJgh food, rrtrple irll srruggle wirh eddr oth€r in ordeLro €!'r- As o l!fllr, lhde rill be o f@d -- , ond ou, now]nert of on ihdiyiduol fron d c..tair - the move$eni o, on individudl our of o cerrain pla.e which help r€duce ihe populotion of th6t fr Arcih€. b.sic ned is w.ra. Wde. shorroge ocu.s when there is on ircreare of hu,nber of p@ple ro be $pptied. rn owr-popur.t d ore.s, woler is rdior€d, Ir rEB rhoi supplies like ti,tWSS ond ,IWSI can'i $pply enoish worer. Do you hdve enough supply of sai.. in your oreo? Aside f.om food alld worer, shelier is olso ohe o, our inportant heeds. As the populoiion ihcre.!e!, building n.w hoLr!€s or rhelt€r is limit.i. To find solulion to this prcbl€n, some goverihent og.ncies dnd orhs non{ov€Ihrehl offi.iofs (N6O) .onvefied sot@ ti.elields, du,np site. dnd nountcirlr inlo flbdivisions dnd relidentiols. Sut whot uould be ths effect o{ coMrtiig .i@fields to .6id€nri6l uits in our food supply? z , 2 Z Z :'", becouse there ore no enough space for prcpex garbage dkposol. ^s o r€sulr, sore peoPle lend to ihrow'their gorbdge onywh.f€. oorbdge baones brc{niry ond rursing ground of iEecrs and onidols ihot @se horm ro pe.ple. Dec.yiry garboge olso produces r,hpleaiant odor ard ehen burn if pmduces pois.nour qds @lled nelhohe As ihe populdtion incr€a3*, the 9d6.9e dso incraes. nris is T't ,,8 T H Wha you de living in on oa-populdi.d pla@, you moy oqaiae halrh prcblerns. Ir is be@@. the woi.r srpply is limit.d ihct will l..d you to poor hygi.ni. hobirs. In plo.4 like rhis, the surrouhdiigs naybe uniidy. o focrorthoi @uld oko cfFe.t your h4l'th. The common oilments rhot yd @uld oc$rire in ovesfDpllar€d ploces ore bEnchil is, o5l hnq. diqrrha and rube.culosis. 7,\ ,\\ \1" 6. Lnck of Herlrh sarvice llosi Pelple in 6n oM-populci€d 6ra 90 ro rubli. heilrh @trtas ond governhent hospirols be6u.e ii prcvides fr@ @Eulrorion oid los @sr rEdicdrions. A3 a ..suli, lh€s€ gow.nnenr dg€rciB b.@ne itud.4$re in mcetiig ihe n eds b..ou!€ df ihsrffici€nr funds. Lock of medicol personnel ,o odmaiisi€I is also s problen in mosr hosptols ev€n rhere or. od.audtc supply of hedicire!. 7_ Do you how wlry rhe crim€ roi€ hexs ih becdur€ fiDre pe.ple o.e fnJrrct€d d@ ro sLffici€.i naE io supp.rr their forniliG. ouf country inclY{ses? If is uh.mploym€ni dnd hdve no arinet .re u$dv gr€{rer ia dn dq-popltdled ra whq. tl, , a, v, tlr I E. Air ard Wat€r Pollutioh How dir be.o'nes pollut€d? I11€ dir b@'n€s p.llurn be.4ne of rhe hormfolgoees thot ser. produ.4 by the fdciori€s and vehicles. Itete {octories ond whi.l6 @ fuel ro run nochiB ond .JBin6. In ,h€ prc.ess, they give our Cdrboh Dioxide ond other ho.6ful gars.r such 6 Nittugei Oxide, Corbon l oioxide dnd Le.d iiio the oir. Do you know whot .ontdbute io ihe incr€asing number of whides qnd foctories? It is ihe inc.6e o, populdtion. As whdt I hove dis.!sse!, wirh a lihired sra.e 9@bd9e disposalie one of the problens thot .o!ld ise i, dh o!er-pop!,.t€d ploce. exn,jple ot thie orc rhos€ pelpl€ livi,rg oh the raverside teid 'ro ,hrou, lheir gEr&ge Hde you seen 'th. P6si9 river or the Tulyahan river? Did you {ind it Whdr do you think i! ihe eff€.t of ihis ih the.re4iures sho lives ih Ahothd f6do.s thal could.on rlbule to wdtd pollutioh dre oil s?ills, gorbqg€ fro,n boa, or ships ahd som€ ihdust.iol wosre. 9. Ite l@96f p4.enroge group. Individuols who orc this grclp. of olr popllarioh is compos.n of the working @pobla of s'rpporting ,heir fomilies nok !-up Though rhas group hol& the lojgeei percenroge of d. populaiion, rhis olso becomer one o{ oveFpopulored probl€]ns b€4use there ore rc jobs awildble fo. oll of iha10. Erergy Shortdge ltere will be on energy shortdge iJ ihe populdtion incre63"l be.dise rhe d.,nand i. €le.iriciry is high. Why is thai wh.n th. PoPqldion inclE.g, rhe d4ord in el4tricity is high? Ir B be.ouse there $,ould be 8to.e hdsat dnd blildirys to lighr ond nore el?riric oPPliohces ro run. rt.6rcznho!3.Ef+ed Whor is rhe grernho@ eff€.r? In whoi say il c.uld offect c2 6re.hhG. effed is rhe wdrniltg of rhe drltlosphee. lvhen the 5un worft rhe.nrrh s1jrf.@, sone of rhe h@r go€J bo.k ro rhe ornos?herc. Air an the dtnDsphere which is C@boi Dioxid. ,rops ihe heot 6hd it mok6 the a.th very worm. As ihe populdtion coniinuou!|,l gtol4 , the gt@rl$use etfe.t b@res no.e visible. Ir is becaosu ,hera ore mo.e focrories snd whicl.s iha, produce wdst€s ond fuma5 which cduses more C{.bo. Diodde ir the ormosphere. As a rcsutt, ,herc eiould be nore h4, ,rop in the ornosphere uhich osk6 th. @ih nuch wornerIf this will hoppen continuously, ,h€ fish ih th€ ocah *ill di€, ricerields/f@mlands will dry too due to lh€ wcm clitnole 12. Destruction of rhe Ozone Loyer A5 whot you hove l@med lrheh you de in v5-6, rhot the qzore ldver is 'the proiecrive loy€. of the olnosPhd€. ft protects us {rom the homful effects of ultrdviolei rays of the su. Do you khow ,hot our Ozore lol€t q4. dQ4tt\!ci.d? Il olreadY hod holes lhai dllow the ulrroviolet rdys to .4dt ihe @rrh. How do6 this hdpPei? Does th. in rc$e of poPuldioh h@€ sonething 'to do tr,lh ir? Yes, rhe I6i grov/irts PoPuldiion .odribuied o lot be@use 6 th' populotion incre3es, rhe u5e of refrigerd'tors, d€rosol lProvs 6nd pl4srics 6bo ihcre&s6. The sid producls coiiojn chemicol called Chlorofluorocdrbons (CFCS) which is mix wafh ihe dir in ihe ormosPher€. As o resulr. ihe hcrmfirl chernicol r€oches the Prolectiw ldver dnd lhrowh. hole in {hid ult@iolzi cahders aid cai4.ct3 ,F.*Y.iis hi!586$q€9.7,- Ho$ doas dcid rdin form? Is cid roii hdmful ro rEn? In the prcvious dis.ussions, yodt€ t.on€d rhd more vel .1e3 dnd fdctori€s or€ necded fo het the iii:.e.siry number o{ P@Pla. Lefs now fihd af hd f@tot.i€s dnd vehicle! .ontribure in the forrEtion of ocid When foctories 6nd whi.ler give off woste gd..3 ,hot will ,nix on lhe noisture i. rhe oir, it will ihen Produ.e sulPhu.i. ocld dnd Nitri. o.id. 'Ihe clol,Jd folb will ,h€h obsorb rhese ccids ond ehei ihe clold f.lls os .oin, ih. ccid is ahady Pdrr of itU/ha d.id ftin falls oh lok"!, ,46 or ocan ih€ fish sill die d.d if h fdlls oh fopnlonds,lhe pldni. together oith the soil B desrroyed. When you inhole dir with Niiric acid, your blood will los. irs @pobilily io fonspori Oxyg€h to your diff€.ai bodY Po.i3. ScieniisB include other rorns oJ dcidic pr€cipiigrion. Thes€ drc nisi, Do you krcw ihot Nuclerr power slotionr Use .adiodctive ,ndie.ials in producirE fuels, yet, rhey do and those .odioactiw rndlqlotE gi\e otf radio'ting en.rgy thoi is harmrul 'to livirq thilEs. wlren rodiotion enlert ihe body ot living things it {ill srq rhere for o lorg ,eriod of ri'ne. Exonple fhe rodiqtion vG srilled to the c.m. Then rhe @rn will be aie by rhe chicken, the .odiotion o the c.rn 'rill also 'tronsf€r to the chi.k€n. Wha on individuol als ihe nat of the chickeh sith mdiarion, helshe rill .ko oblorb ihe rodi@.tirc mtaid that will destrcy hB/her .€lls ond ruket hnn/hd si.r. Over-populoiion .on leld to food shoridg€, wdter shorroqe, housiB probl€ms, qdrbog€ probl€rs, lock of halrh sdi.e. tisa ol clit@ rote, oir ond woi€r pollution, uhanpl6ynat, eiergy 5horr69e, grenhoq3€ efreci, desrruction o( th. ozo@ lat/e?, rci.l roi. olld e.l€d. wattaFormation of m, n and rFormation of m, n, r, h, k, b and pPre-cursive formation of m, n, and rMake mcq quiz with 4 option in which one is correct -'10 Basis of Material Science • .....;;;";;;"~~;;,,;;,,,,;.;.,,;;,,,;,,;.;,.,------------ 6. Temporary materials: Some materials are meant to be placed in the oral cavity for a short period of time for different reasons. • Temporary crowns: While a permanent crown is prepared in the dental laboratory, the patient must wait for few days before it can be fabricated and cemented into place. Does patient experience any problems during this time period? If the tooth is vital (the pulp is alive), the patient is likely to experience pain and sensitivity while eating and drinking, also it looks unesthetic. What can be done to solve this problem? A temporary crown is placed before the patient leaves the clinic. It is constructed and luted in the same appointment in which the crown preparation is done. Temporary crowns are not very strong or esthetic but they serve adequately till the permanent crown is ready to be cemented. • Temporary restorations: Sometimes it is difficult to decide immediately the best line of treatment for a particular tooth. The exact condition of the pulp may not be obvious to the dentist from the patient's symptoms. A dentist removes all or part of the decay and then places a temporary restoration to have time to observe the behaviour of the pulp or to give the pilip time to heal before deciding the further treatment required. Classification based on Location of Fabrication 4,9 Materials can be classified based on the location of fabrication into: • Direct restorative materials. • Indirect restorative materials Direct restorative materials: They include those materials which are used to restore cavity preparations directly in the oral cavity (Box 1.5). Box 1.5: Examples of direct restorative materials Amalgam, composites, glass ionomer and other materials, which set by chemical reactions in the mouth. Indirect restorative materials: It includes those restorations which must be fabricated outside the mouth, indirectly on a cast/ model/ die, because their processing condition would harm oral tissues. Materials used in the construction of such prosthesis are called indirect restorative materials (Box 1.6). Box 1.6: Examples of indirect restorative materials Gold inlays, crowns of metal, ceramic and polymers, which are processed at elevated temperatures. Some indirect composite restorations can be processed under specific wavelength of light, e.g. Ceramage. Classification based on Longevity of Use 1. Permanent restorations: These restorations are not planned to be replaced for a particular time period. Though they are referred to as permanent, actually they are not, e.g. fillings, crowns, bridges and dentures do not last forever (Fig. 1.5). 2. Temporary restorations: These restorations are planned to be replaced in a short period of time, such as few days to weeks. For ~ Permanent C/) c c -.2 0 c- :;::; Cll co Interim ~ Q; 0 .8ll::1iJ C/) o~ Cll a:: c:=:J Temporary Time period Fig. 1.5: Diagram depicting the time period of use of a restoration. (Arrow in permanent restoration depicts that such restorations are not planned to be replaced for a long period of time.) Introducton to Dental Materials Dental materials Box 1.7: Characteristics of metals 1. High thermal and electrical conductivity 2. Ductility (pure metals are very soft and they can be bent without breaking) 3. Opacity (they do not transmit light) 4. Luster (they have a surface that strongly reflects light and appears bright and shiny) 5. They tend to dissolve to some extent in water or other aqueous solutions, producing cations. 6. All metals are white (actually gray) except for gold, which is yellow, and copper, which is reddish. 7. All metals are solid at room temperature except mercury, which is liquid at room temperature and is used with silver alloys as amalgam. 8. All metals have high melting temperatures because of high strength of the metallic bond that holds the atoms together. 3. Polymers 4. Composites Composites are mixtures of two or more of the first three classes in which the different components remain distinct from one another in the final structure. A common example is composite resin. Fig. 1.7a: Three-dimensional structure of iron (metal) Metals Metals are the oldest of the three classes of materials that have been used as dental materials. Metals are characterized by metallic bonds (Box 1.7) which will be discussed in the next chapter. Metals solidify with their atoms in a regular or crystalline arrangement (see Chapter 2), often in the form of a cube (Fig. 1.7a). example, temporary fillings done in a tooth during root canal treatment, which have to be replaced within 2-4 days during subsequent visits. They are used to protect the tooth and provide function till the final restoration is done. 3. Interim restoration: At times, dental treatment requires "long-term" definite temporary restorations or "interim" restorations. For examle, a 7-year-old child, met with trauma and fractured one of his central incisors. A large composite build- up may serve his immediate requirement until the root formation is completed and a permanent crown is placed. 5 Classification based on the Chemical Nature of the Material These are the atoms that make up a material and the way they are bonded together determine the properties of that materiaLS Weak bonds make for weak materials and vice versa (Table 1.4). Materials can be classified into different categories based on their primary atomic bonds (Fig. 1.6): 1. Metals 2. Ceramics Fig. 1.6: Classification of dental materials based on chemical nature 12 Basis of Material Science Box 1.9: Benefits of ceramics in dentistry 1. Many ceramic oxides are used as pigmenting agents. These oxides produce good range of colors. Due to this characteristic, we are able to match almost any tooth color with good esthetic results. 2. They are inert, i.e. not chemically reactive. This quality provides ceramics with good bio- compatibility. 3. Ceramic materials are translucent, like natural teeth. This translucency gives the ceramic crown a more natural appearance than any other dental material. Fig. 1.7b: Internal arrangement of tetrahedral structure of ceramic (silica) four large oxygen atoms surround smaller silicon atom Ceramics A ceramic is a compound formed by the union of a metallic and a non-metallic element (Box 1.8). Most of these materials are oxides, formed by the union of oxygen with metals such as silicon, aluminum, calcium and magnesium (Fig.1.7b). Ceramics may be simple or complex. Examples of simple ceramics are alumina and silica. Examples of complex ceramics are feldspar (potassium aluminum silicate) and kaolin (hydrated aluminum silicate). Ceramics may be crystalline or non- crystalline (i.e. amorphous). Porcelain is a specific type of ceramic used extensively in dentistry (Box 1.9). Box 1.8: Characteristics of ceramics 1. High melting points. 2. Brittleness, which means they cannot be bent or deformed (no sliding) to any extent without actually cracking and breaking. 3. They are poor conductor of heat and electricity. 4. They are chemically inert. 5. They have excellent esthetic result in terms of matching natural teeth. Fig. 1.8: Stucture of synthetic polymer Polymers They are the latest addition (early to mid- 1900s) to dental materials. Most of the polymers are nowadays synthesized by humans. Polymers are giant, long-chain organic molecules (Fig. 1.8). Polymers are characterized by covalent bonds within each molecule, giving them tremendous strength in a single direction. Try to break a nylon rope by pulling it! They are poor conductors of heat and electri- city. Most polymers have a structure containing thousands of carbon atoms linked together like beads on a string. Others, such as silicone polymers are formed with silicon-oxygen bonds. Introducton to Dental Materials Table 1.4: Characteristics of different materials 13 Characteristics Bond Properties Crystal structure Metals Metallic bonding High strength and hardness, high electrical and thermal conductivity BCC, FCC, or HCP unit cells Ceramics Ionic or covalent bonding, or both High hardness and stiffness, electrically insulating, refractory, and chemically inert Crystalline or amorphous Polymers Covalent bonding Low sensitivity, high electrical resistivity, and low thermal conductivity, strength and stiffness vary widely Amorphous and crystalline Composites Composites are combinations of any of the basic ceramic, metallic and polymeric materials (Box 1.10). Each material that makes up composites is called a phase. Their properties tend to be somewhere between those of their basic constituents and are used to enhance their performance, longevity and handling chracterstics. Box 1.10: Types of composites in dentistry 1. Ceramic - metallic composite: Tungsten carbide bur. 2. Metal - polymer composite: Die materials in dental laboratory. 3. Ceramic - polymer composite: Enamel, dentin, bone and restorative composites. A composite is a kind of "combination" of materials, which compliment each other. The properties lacking in one material are compensated by those of the other material. For example, restorative composite has two phases, namely resin and fillers. Teeth and bones are examples of natural composites. Enamel is a composite of hydroxyapatite (which is a ceramic material) and protein (which is a polymer). EVALUATION OF DENTAL MATERIALS Most manufacturers of dental materials maintain a quality assurance programme (As per international standard like ADA specifications) and materials are thoroughly tested before being released into the market for dental practitioner (Fig. 1.9). Laboratory Evaluations Most ADA/ ANSI specifications involve laboratory tests. The tests performed as per these specifications are useful but they all are performed in vitro, (carried out in the laboratory away from the clinical conditions) which have a lot of limitations in clinical practice.lO Clinical Notes 1. For example, most of the direct restorative materials are tested for their compressive strength but ultimately the material is subjected to a combination of compressive, tensile and shear stresses, which may decide the final success or failure of the material under masticatory load. 2. Similarly upper dentures mostly fracture along the midline because of bending. Hence a bending or transverse strength ~B-a-s-is-o-f-M-a-t-e-ria-I-S~c-ie-n-c-e-------------- ---------. test is far more meaningful for denture base materials than a compression test. Clinical Trials The majority of new materials are subjected to extensive clinical trials normally in co-operation with a dental college or hospital departments prior to their release. CONCLUSION As the number of available materials is going up, it is important that the dentist remains more aware about new products so that their judgement about the selection of material remains successful. Materials which have not been thoroughly evaluated should be avoided, specially with clinical dentistry falling under Consumer Protection Act (CPA). I Research and development I iI Manufacturer/analysis Ideal requirements for clinical use: Thermal, optical, mechanical, chemical, biological Available materials and their properties are evaluated Launch of new I product Choice and selection of material by the dentist Critical assessment based on clinical performance I I H feedback to IIn a single domesticated grain seed, one might see the bud of great civilizations. The birth of agriculture was a turning point in humans' social development, as stable food supplies enabled people to transcend the constraints of food gained by hunting and gathering. After that, people were able to settle down and experience population booms. As one of the major areas around the globe where agriculture originated, China has contributed to the world's domesticated rice, millet, buckwheat and soybeans. Archaeological studies have unveiled that the planting of rice originated around 10,000 years ago in the lower reaches of the Yangtze River, leading to the eventual replacement there of hunting and gathering practices dating back 5,000 to 6,000 years. "It marked the formation of a rice-based agricultural society in the area," said Zhao Zhijun, an archaeologist at the Chinese Academy of Social Sciences. Archaeological studies of the origins of rice-based agriculture are an important part of a national project tracing the origins of Chinese civilization itself. President Xi Jinping has greatly valued the project. At a group study session of the Political Bureau of the Communist Party of China Central Committee on May 27, 2022, Xi, who is also general secretary of the CPC Central Committee, emphasized the significance of the project and the role that archaeological studies play in better understanding Chinese civilization. The project to trace the origins of Chinese civilization, in addition to finding signs of human activity more than 1 million years ago, has also proved that China's history includes 10,000 years of culture and more than 5,000 years of civilization. The project has provided clear knowledge of the origins and formation of Chinese civilization, the history of its development, the process of the formation and development of its pluralistic and integrated pattern, and the characteristics of the civilization and why it was formed in such a way, he added. This was not the first time that Xi emphasized the importance of the origin-tracing project. Since the 18th National Congress of the CPC in 2012, Xi has toured more than 100 historical and cultural locations and issued many instructions related to archaeology and the origin-tracing project. During the 23rd group study session of the Political Bureau of the CPC Central Committee in 2020, Xi called for giving more attention to archaeological research and letting historical facts speak for themselves. "This will provide strong support for our efforts to carry forward the best of traditional Chinese culture and increase our cultural confidence," said Xi. The origin-tracing project has been carried out since 2002. Its ongoing fifth phase, which started in 2020, involves the participation of more than 500 researchers from 29 institutes across the country. It primarily centers on several ancient capital sites, including the Liangzhu site in Hangzhou, Zhejiang province, the Taosi site in Xiangfen county, Shanxi province, the Shimao site in Shenmu, Shaanxi province, and the Erlitou site in Luoyang, Henan province, from 3,500 to 5,500 years ago, as well as other settlements mainly along the basins of the Yellow, Yangtze and Liaohe rivers. The project has also expanded to a wider geographic and chronological framework to decode how Chinese civilization emerged and how its diverse elements formed a unity. Excavation of the Liangzhu site, which is over 5,000 years old and is one of the major sites covered in the origin-tracing project, has yielded an inner city covering 3 million square meters and an outer city of 6.3 million sq m, making it the world's largest capital at the time. It also had a giant water control system, which contributed to the formation of a rice-based agricultural society. By calculating the earthwork volume, archaeologists found that building the entire ancient city, the water control system and Mojiaoshan — a 10-meter-tall man-made terrace in the center of the city — required 10,000 people working daily for seven-and-a-half years. The discoveries show that Liangzhu had a kingship able to organize people for large-scale public construction, and its social differentiation, emergence of the city concept and existence of a kingship prove that it became a civilized society, said Wang Wei, a veteran archaeologist at the Chinese Academy of Social Sciences. Significant topic Wang said that tracing the origins of a civilization is a significant topic in the research of human history. Over the years, the Chinese project has provided China's answer to how to define civilizations. In 2022, Xi commended the efforts and stressed that the project has made creative contributions to the research on tracing the origins of the world's civilizations. Wang said: "International academia has proposed three indispensable elements for a civilized society based on features of Mesopotamian and Egyptian civilizations: written characters, metallurgy and the city concept. But we can find that some of the three elements were absent in many ancient civilizations. For example, the Mayan civilization had no metallurgy, while the Incan civilization didn't have written characters." Western scholars believe that Chinese civilization began with the Yinxu Ruins in Anyang, Henan province, a capital of the late Shang Dynasty (c.16th century-11th century BC), based on the discovery of inscribed oracle bones from that time. However, Chinese archaeologists don't agree. With continued archaeological research, international academia now believes that places around the world can propose criteria for civilization based on their own ancient social development. China's archaeological studies have shaped the nation's criteria in defining a civilization: the development of productivity, an increase in population, the appearance of cities, social differentiation and the emergence of kingship and state. "These criteria are suitable for identifying other civilizations as well," said Wang. "Civilizations have in common the appearance of kingship and state. They are only different in the ways of imposing kingship and the forms of state." In China, kingship and state "were shown by exquisite jade and bronze ritual artifacts, grand palaces and magnificent mausoleums imitating aboveground palaces", he added. "In Mesopotamia and ancient Egypt, they were demonstrated through superb stone temples, pyramids and large-scale tombs." Multidisciplinary subject President Xi said in 2020 that archaeologists should work closely with researchers from other fields to make an interpretive analysis of material remains. Zhang Chi, a professor of archaeology at Peking University, said that since material remains are often the research focus of archaeological studies, these should not only be observed with the eyes, but also studied using scientific and technological tools. Therefore, from the perspective of research methods, archaeology is by nature a multidisciplinary subject, Zhang added.Formation of Heavy Elements and Synthesis of Elements in the Laboratory