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Journal of Assisted Reproduction and... Nov 2022Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6-20% of females in reproductive age. Most symptoms of PCOS arise... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6-20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail.
Topics: Humans; Pregnancy; Female; Polycystic Ovary Syndrome; Hyperandrogenism; Insulin Resistance; Reactive Oxygen Species; Sexual Maturation; Inflammation; Infertility; Gonadotropin-Releasing Hormone; Tumor Microenvironment
PubMed: 36190593
DOI: 10.1007/s10815-022-02625-7 -
Best Practice & Research. Clinical... Sep 2021Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by... (Review)
Review
Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by environmental factors such as obesity or endocrine disrupting chemicals. The last 30 years have been marked by a constant secular trend toward earlier age at onset of puberty in girls and boys around the world. More recent data, although more disputed, suggest an increased incidence in idiopathic central precocious puberty. Such trends point to a role for environmental factors in pubertal changes. Animal data suggest that the GnRH-neuronal network is highly sensitive to endocrine disruption during development. This review focuses on the most recent data regarding secular trend in pubertal timing as well as potential new epigenetic mechanisms explaining the developmental and transgenerational effects of endocrine disrupting chemicals on pubertal timing.
Topics: Animals; Endocrine Disruptors; Female; Humans; Male; Obesity; Puberty; Puberty, Precocious; Sexual Maturation
PubMed: 34563408
DOI: 10.1016/j.beem.2021.101579 -
Nature Nov 2021The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development....
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
Topics: Adolescent; Aged, 80 and over; Animals; Child; Child Development; Estrous Cycle; Female; Homozygote; Humans; Hypothalamus; Insulin-Like Growth Factor I; Male; Melanocortins; Menarche; Mice; Nutritional Status; Phenotype; Puberty; Receptor, Melanocortin, Type 3; Sexual Maturation; Time Factors; Weight Gain
PubMed: 34732894
DOI: 10.1038/s41586-021-04088-9 -
Best Practice & Research. Clinical... Jan 2022Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset... (Review)
Review
Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Pubertal onset is regulated by genetic, nutritional, environmental, and socio-economic factors. Disturbances affecting pubertal timing result in adverse health conditions later in life. Human genetic studies show that around 50-80% of the variation in pubertal onset is genetically determined. The genetic control of pubertal timing has been a field of active investigation in attempt to better understand the neuroendocrine control of this relevant period of life. Large populational studies and patient cohort-based studies have provided insights into the genetic regulation of pubertal onset. In this review, we discuss these discoveries and discuss potential mechanisms for how implicated genes may affect pubertal timing.
Topics: Gonadotropin-Releasing Hormone; Humans; Puberty; Puberty, Delayed; Sexual Maturation
PubMed: 35183440
DOI: 10.1016/j.beem.2022.101618 -
The FEBS Journal Jan 2023Mammalian puberty and Drosophila metamorphosis, despite their evolutionary distance, exhibit similar design principles and conservation of molecular components. In this... (Review)
Review
Mammalian puberty and Drosophila metamorphosis, despite their evolutionary distance, exhibit similar design principles and conservation of molecular components. In this Viewpoint, we review recent advances in this area and the similarities between both processes in terms of the signaling pathways and neuroendocrine circuits involved. We argue that the detection and uptake of peripheral fat by Drosophila prothoracic endocrine cells induces endomembrane remodeling and ribosomal maturation, leading to the acquisition of high biosynthetic and secretory capacity. The absence of this fat-neuroendocrine interorgan communication leads to giant, obese, non-pupating larvae. Importantly, human leptin is capable of signaling the pupariation process in Drosophila, and its expression prevents obesity and triggers maturation in mutants that do not pupate. This implies that insect metamorphosis can be used to address issues related to the biology of leptin and puberty.
Topics: Animals; Humans; Leptin; Puberty; Drosophila; Mammals; Signal Transduction; Obesity; Sexual Maturation
PubMed: 35607827
DOI: 10.1111/febs.16534 -
Ciencia & Saude Coletiva Sep 2022This study aimed to investigate the relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers. This was a population-based...
This study aimed to investigate the relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers. This was a population-based cross-sectional study, conducted with 345 teenagers, aged 10 to 19 years, between 2018 and 2020. In this study, data referent to sociodemographic and anthropometric variables, blood pressure, and sexual maturation were collected. The data analysis was performed by applying the Principle Component Analysis (PCA), which generated three components and then tested the correlation between sexual maturation and the generated components. Most of the teenagers were female (53%), normotensive (66.1%), and with a normal weight (73%). A positive correlation was found between breast development and component 1 and component 2, as well as a negative correlation between the breasts and component 3. In the boys, the development of genitals and pubic hair was positively correlated with component 2 and inversely correlated with component 3. It could therefore be concluded that there is a relationship between sexual maturation and the anthropometric and blood pressure indicators, which proved to be representative variables for cardiovascular risk in teenagers, even if not in their entirety.
Topics: Adolescent; Anthropometry; Blood Pressure; Cross-Sectional Studies; Female; Humans; Male; Sexual Maturation
PubMed: 36000648
DOI: 10.1590/1413-81232022279.04622022 -
Environment International Mar 2022In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD)....
In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD). In this regard, we hypothesized that exposure to microplastics is a potential risk factor for ASD. To evaluate the validity of this hypothesis, we initially examined the accumulation of polyethylene (PE) in the brains of mice and then assessed the behavioral effects using mouse models at different life stages, namely, prenatal, post-weaning, puberty, and adult models. Based on typical behavioral assessments of autistic traits in the model mice, we established that ASD-like traits were induced in mice after PE feeding. In addition, we examined the induction of ASD-like traits in response to microplastic exposure using positron emission tomography, magnetic resonance spectroscopy, quantitative real-time polymerase chain reaction, microarray, and microbiome analysis. We believe these findings provide evidence in microplastics as a potential risk factor for ASD.
Topics: Animals; Autism Spectrum Disorder; Female; Microplastics; Plastics; Pregnancy; Risk Factors; Sexual Maturation
PubMed: 35134716
DOI: 10.1016/j.envint.2022.107121 -
Cells Mar 2022Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and... (Review)
Review
Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and females. Hypothalamic KPs and KPR display a high degree of sexual dimorphism in expression and function. KPs act on KPR in gonadotropin releasing hormone (GnRH) neurons and induce distinct patterns of GnRH secretion in males and females. GnRH acts on the anterior pituitary to secrete gonadotropins, which are required for steroidogenesis and gametogenesis in testes and ovaries. Gonadal steroid hormones in turn regulate the KP neurons. Gonadal hormones inhibit the KP neurons within the arcuate nucleus and generate pulsatile GnRH mediated gonadotropin (GPN) secretion in both sexes. However, the numbers of KP neurons in the anteroventral periventricular nucleus and preoptic area are greater in females, which release a large amount of KPs in response to a high estrogen level and induce the preovulatory GPN surge. In addition to the hypothalamus, KPs and KPR are also expressed in various extrahypothalamic tissues including the liver, pancreas, fat, and gonads. There is a remarkable difference in circulating KP levels between males and females. An increased level of KPs in females can be linked to increased numbers of KP neurons in female hypothalamus and more KP production in the ovaries and adipose tissues. Although the sexually dimorphic features are well characterized for hypothalamic KPs, very little is known about the extrahypothalamic KPs. This review article summarizes current knowledge regarding the sexual dimorphism in hypothalamic as well as extrahypothalamic KP and KPR system in primates and rodents.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Male; Sex Characteristics; Sexual Maturation
PubMed: 35406710
DOI: 10.3390/cells11071146 -
Frontiers in Cell and Developmental... 2021Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual... (Review)
Review
Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual maturation in virtually all animals and by that the two main environmental-dependent developmental decision points. Sexual maturation and metamorphosis are controlled by steroid receptors and thyroid receptors, respectively in vertebrates, while both processes are orchestrated by the ecdysone receptor (EcR) in insects. The regulation of these processes depends on environmental factors like nutrition, temperature, or photoperiods and by that NRs form evolutionary conserved mediators of phenotypic plasticity. While the mechanism of action for metamorphosis and sexual maturation are well studied in model organisms, the evolution of these systems is not entirely understood and requires further investigation. We here review the current knowledge of NR involvement in metamorphosis and sexual maturation across the animal tree of life with special attention to environmental integration and evolution of the signaling mechanism. Furthermore, we compare commonalities and differences of the different signaling systems. Finally, we identify key gaps in our knowledge of NR evolution, which, if sufficiently investigated, would lead to an importantly improved understanding of the evolution of complex signaling systems, the evolution of life history decision points, and, ultimately, speciation events in the metazoan kingdom.
PubMed: 34178983
DOI: 10.3389/fcell.2021.653792 -
Current Biology : CB Apr 2022Adequate nutrition is essential for normal reproductive function, which is vital for species to survive. In humans and other mammals, starvation and undernutrition...
Adequate nutrition is essential for normal reproductive function, which is vital for species to survive. In humans and other mammals, starvation and undernutrition deplete fat reserves and cause weight loss, attenuating the function of the reproductive axis and causing hypogonadism. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) spend 7 months of every year in hibernation without food and water. Hibernating squirrels alternate between periods of torpor and interbout arousal (IBA), when animals temporarily return to an active-like state. The physiological significance of IBA is unclear, but it is thought to be essential for hibernation in animals that drop their body temperature to 2°C-4°C during torpor. Here, we report that juvenile male ground squirrels initiate reproductive maturation during their first hibernation season, despite prolonged undernutrition and profound weight loss. We show that the hypothalamic reproductive axis undergoes activation during interbout arousals in the middle of hibernation, triggering production of luteinizing hormone and testosterone, and promoting testicular growth. Initiation of sexual maturation is circannually entrained and is independent of physiological state, ambient temperature, and food availability. Our study suggests a role for interbout arousals during hibernation and uncovers the neurophysiological mechanism of reproductive axis activation during conditions of extreme negative energy balance. VIDEO ABSTRACT.
Topics: Animals; Hibernation; Male; Malnutrition; Sciuridae; Sexual Maturation; Weight Loss
PubMed: 35245461
DOI: 10.1016/j.cub.2022.02.032