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Polycystic ovary syndrome (PCOS) is one of the most common reproductive and endocrine disorders in women of childbearing age, and the pathogenesis is unknown. Insulin resistance, hyperandrogenism and obesity are important pathophysiological basis. Glucose-dependent insulinotropic peptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. Literature studies have shown that GIP is correlated with insulin resistance, hyperandrogenism, obesity and other characteristic changes of PCOS, and it may contribute to the onset and progression of PCOS by affecting the function of hypothalamic-pituitary-ovarian axis, suggesting that GIP is associated with PCOS. This paper reviews the research progress of the correlation between GIP and PCOS. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we aimed to understand the role of non-coding RNA in egg production by analyzing the transcriptome of chickens. We collected tissues from both low-yielding and high-yielding Bian chickens, focusing on the hypothalamus, pituitary, and ovaries, which are key to reproduction. Using advanced sequencing technology, we identified circular RNAs that differed between high and low egg producers. Our results revealed that these circRNAs are involved in crucial processes like cell development, nervous system function, and protein regulation. We also discovered networks of RNA interactions that may influence egg production. These findings enhance our understanding of the genetic factors that control egg production, potentially leading to improved breeding strategies for better poultry production and health, benefiting farmers and consumers alike. The hypothalamic–pituitary–ovarian (HPO) axis plays a pivotal role in the regulation of egg production in chickens. In addition to the traditional understanding of the HPO axis, emerging research highlights the significant role of circRNAs in modulating the functions of this axis. In the study, we collected hypothalamus, pituitary, and ovarian tissues from low-yielding and high-yielding Bian chickens for transcriptome sequencing. We identified 339, 339, and 287 differentially expressed (DE) circRNAs with p_value < 0.05 and |log2 (fold change)| ≥ 1 in hypothalamus, pituitary, and ovarian tissues. The Gene Ontology (GO) enrichment analysis for the source genes of DE circRNAs has yielded multiple biological process (BP) entries related to cell development, the nervous system, and proteins, including cellular component morphogenesis, cell morphogenesis, nervous system development, neurogenesis, protein modification process, and protein metabolic process. In the top 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we observed the enrichment of the GnRH signaling pathway in both the hypothalamus and the pituitary, solely identified the GnRH secretion pathway in the pituitary, and discovered the pathway of oocyte meiosis in the ovary. Furthermore, given that circRNA primarily functions through the ceRNA mechanism, we constructed ceRNA regulatory networks with DE circRNAs originating from the GnRH signaling pathway, GnRH secretion, ovarian steroidogenesis, steroid hormone biosynthesis, and the estrogen signaling pathway. Finally, several important ceRNA regulatory networks related to reproduction were discovered, such as novel_circ_003662-gga-let-7b/miR-148a-3p/miR-146a-5p/miR-146b-5p and novel_circ_003538-gga-miR-7464-3p-SLC19A1. This study will contribute to advancements in understanding the involvement of circRNAs in the HPO axis, potentially leading to innovations in improving egg production and poultry health. [ABSTRACT FROM AUTHOR]

Minipuberty is a term describing transient postnatal activation of the hypothalamic–pituitary–gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring. [ABSTRACT FROM AUTHOR]

Management practices during the rearing of dairy heifers should allow an adequate body growth and reproductive development to attain puberty several months before the first conception. Proposed target age and body weight (BW) at first calving for Holstein heifers are between 22-24 months and 82% of mature BW, respectively, for which heifers must conceive at around 15 months of age with 60% of their mature BW. Pre- and postweaning feeding level has effects on feed efficiency, behavior, energy metabolism and body and reproductive development, while social environment during rearing, specifically the social dominance and social regroupings, is known to affect energy metabolism, feeding behavior and body and reproductive development of the heifer. In Uruguay, the information published regarding the management of the dairy heifer is scarce. The aim of this review is to briefly assess the main factors affecting the onset of puberty, and to present an integrative approach of the information generated in Uruguay regarding the effects of modifying the feeding level and social environment during the rearing period on body development, metabolism, and onset of puberty in dairy heifers. In addition, we make a proposal of knowledge gaps that should be addressed in future studies.

The hypothalamic–pituitary–ovarian (HPO) axis plays a pivotal role in the regulation of egg production in chickens. In addition to the traditional understanding of the HPO axis, emerging research highlights the significant role of circRNAs in modulating the functions of this axis. In the study, we collected hypothalamus, pituitary, and ovarian tissues from low-yielding and high-yielding Bian chickens for transcriptome sequencing. We identified 339, 339, and 287 differentially expressed (DE) circRNAs with p_value < 0.05 and |log2 (fold change)| ≥ 1 in hypothalamus, pituitary, and ovarian tissues. The Gene Ontology (GO) enrichment analysis for the source genes of DE circRNAs has yielded multiple biological process (BP) entries related to cell development, the nervous system, and proteins, including cellular component morphogenesis, cell morphogenesis, nervous system development, neurogenesis, protein modification process, and protein metabolic process. In the top 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we observed the enrichment of the GnRH signaling pathway in both the hypothalamus and the pituitary, solely identified the GnRH secretion pathway in the pituitary, and discovered the pathway of oocyte meiosis in the ovary. Furthermore, given that circRNA primarily functions through the ceRNA mechanism, we constructed ceRNA regulatory networks with DE circRNAs originating from the GnRH signaling pathway, GnRH secretion, ovarian steroidogenesis, steroid hormone biosynthesis, and the estrogen signaling pathway. Finally, several important ceRNA regulatory networks related to reproduction were discovered, such as novel_circ_003662-gga-let-7b/miR-148a-3p/miR-146a-5p/miR-146b-5p and novel_circ_003538-gga-miR-7464-3p-SLC19A1. This study will contribute to advancements in understanding the involvement of circRNAs in the HPO axis, potentially leading to innovations in improving egg production and poultry health.

Minipuberty is a term describing transient postnatal activation of the hypothalamic–pituitary–gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring.

BackgroudBeta-cypermethrin and emamectin benzoate are widely used for the prevention and control of pests in the greenhouse planting industry, and their combined exposure may increase the accumulation of beta-cypermethrin and emamectin benzoate in organisms and affect human health. ObjectiveBased on the changes in reproductive hormone levels in the hypothalamic-pituitary-ovarian (HPO) axis, to investigate the effect of combined exposure to beta-cypermethrin and emamectin benzoate on the estrous cycle of female mice. MethodsTwenty-four healthy adult SD rats were randomly divided into a blank control group, a beta-cypermethrin group (Beta-CYP, 53 mg·m−3), an emamectin benzoate group (EMB, 8 mg·m−3), and a beta-cypermethrin and emamectin benzoate combined exposure group (Beta-CYP+EMB, Beta-CYP 53 mg·m−3 + EMB 8 mg·m−3). Six rats in each group were exposed to the designed treatment protocol by aerosol inhalation 6 d a week for 13 weeks. The general condition of the rats was observed in real time during the treatment. From the 12th week of exposure, a 10-day reproductive tract smear was performed on the rats to observe the estrous cycle. The rats were neutralized on the second day after the end of the treatment protocol, and the ovarian tissues were stained with HE to observe histopathological changes. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured by ELISA. Experimental results were expressed as mean ± standard deviation (\begin{document}$ \overline{x}\pm s $\end{document}). One-way ANOVA was used for comparison among groups, and LSD test for pairwise comparison between groups. The significance level was α=0.05. ResultsAfter four weeks of the treatment protocol, the rats in the Beta-CYP group and the Beta-CYP+EMB group continued to be hyperactive and irritable, while the EMB group showed symptoms of mental disorder, decreased activity, and slow response. On the 90th day of the treatment protocol, the body weight of rats in the control group increased to (314.51±2.44) g, and that in the Beta-CYP+EMB group only increased to (253.47±1.50) g. There was no abnormal cellular morphology in the control group; however, small deeply stained nuclei appeared in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group, and abnormal morphological development of keratinized epithelial cells in the Beta-CYP+EMB group was found. The estrous cycle of rats in the control group was (97.83±4.17) h, and compared with the control group, the estrous cycles of rats in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group were prolonged to (134.33±7.53) h, (126.50±5.28) h, and (156.00±6.66) h, respectively. The results of ANOVA showed that the numbers of leukocytes (527.17±15.83), keratinized epithelial cells (35.67±4.32), and non-keratinized epithelial cells (70.50±4.51) in the vaginal smears during diestrus in the Beta-CYP+EMB group were significantly lower than those in the control group (752.50±28.89, 50.50±2.74, 101.33±7.92) (P

Background: The female reproductive tract is controlled by complex interaction between steroid hormones, gonadotrophins and hypothalamic-pituitary-ovarian axis. A disruption in any of these processes can result in menstrual disturbances. The present study was conducted with an aim to test the hypothesis that subtle endocrinal abnormalities detected by intensive hormone evaluation are associated with menstrual disturbances. Aim & Objective: To compare Prolactin levels in patients with menstrual disturbances with normal healthy fertile females. Methods: The present study was conducted in the Department of Biochemistry. A total of 100 patients reporting to the OPD of Obstetrics and Gynaecology, were studied. Out of 100 patients, 50 patients were with a history of menstrual disturbances, 50 patients of reproductive age group with normal menstrual cycle and with proven fertility were taken as control. Routine investigations were carried out in all the patients. The Prolactin ELISA kit was used for quantitative measurement of prolactin in human serum or plasma. Serial samples were taken for estimation of prolactin. 2 samples were taken on Day 3 of cycle on two consecutive cycles. The serum plasma prolactin reference values used were: Follicular phase up to 22 ng/ml. Result & Conclusion: Considering together, our findings support the hypothesis that women with menstrual disturbances have subtle disturbances in the hypothalamic-pituitary-ovarian axis compared with their fertile counterparts and high prolactin levels play a significant role in the etiology of menstrual disturbances. [ABSTRACT FROM AUTHOR]

The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Egg production is a vital biological and economic trait for poultry breeding. The 'hypothalamic–pituitary–ovarian (HPO) axis' determines the egg production, which affects the layer hens industry income. At the organism level, the HPO axis is influenced by the factors related to metabolic and nutritional status, environment, and genetics, whereas at the cellular and molecular levels, the HPO axis is influenced by the factors related to endocrine and metabolic regulation, cytokines, key genes, signaling pathways, post-transcriptional processing, and epigenetic modifications. MiRNAs and lncRNAs play a critical role in follicle selection and development, atresia, and ovulation in layer hens; in particular, miRNA is known to affect the development and atresia of follicles by regulating apoptosis and autophagy of granulosa cells. The current review elaborates on the regulation of the HPO axis and its role in the laying performance of hens at the organism, cellular, and molecular levels. In addition, this review provides an overview of the interactive network regulation mechanism of the HPO axis in layer hens, as well as comprehensive knowledge for successfully utilizing their genetic resources. [ABSTRACT FROM AUTHOR]

Abstract Background Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. Main text Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. Conclusion More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

Polycystic Ovary Syndrome (PCOS) is a vastly familial, prevalent yet complicated endocrine disorder seen in 5 to 15% of premenopausal women. An estimated one in five ~ 20% Indian women suffer from PCOS. In India, PCOS is a tabooed disorder; If neglected, the condition can prove fatal. However, the past decade has seen the changing discourse in India. PCOS negatively affects reproduction, general health, sexual health, and quality of life. Genetic predisposition of hormonal and non-hormonal factors influence ovary functioning and are responsible for the onset of the syndrome. Hormonal imbalance, metabolic abnormality, and insulin resistance are characteristic features that significantly increase the risk of anovulatory infertility, type 2 diabetes, and cardiovascular diseases. The underlying cause of the path physiology of PCOS is still under the radar, but the derangement of the hypothalamic-pituitary-ovarian axis could be the sweeping reason for the same. PCOS management should address on healthy lifestyle with symptomatic medical therapy and psychological bearing with special emphasis on far reaching side effects and long-term metabolic consequences This review article gives a comprehensive overview of PCOS and the morbidities hooked up with it. It has a notable emphasis on the PCOS guidelines, diagnosis, non-pharmacological, and pharmacological treatments. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP , RLN3 , CARTPT , LHCGR , FSHR , and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.

Background: Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. Main text: Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. Conclusion: More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis. [ABSTRACT FROM AUTHOR]

Objective: Explore how sleep disorders affect female fertility through the hypothalamic-pituitary-ovarian axis. Methods: Eighty women of childbearing age who were admitted to the department of Gynecology and endocrinology of our hospital from October 2018 to October 2021 were selected as the research subjects. According to the evaluation results of Pittsburgh Sleep Quality Index (PSQI), all subjects were divided into a sleep disorder group (n=34) and a non-sleep disorder group (n=46) according to the presence or absence of sleep disorder. PSQI score, serum sex hormone level, menstrual cycle and fertility were compared between the two groups, and the correlation between sleep disorder and female fertility was analyzed by Pearson method. Results: (1) PSQI total score, sleep quality, sleep time, sleep time, sleep efficiency, sleep disorder and daytime dysfunction scores in sleep disorder group were higher than those in control group (P<0.05). (2) The levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the sleep disorder group were higher than those in the non-sleep disorder group, while the level of estradiol (E2) was lower than that in the non-sleep disorder group(P<0.05). (3) The proportion of menstrual disorder in sleep disorder group was higher than that in control group(P<0.05). (4) Comparing the fertility of the two groups, the fertility of the sleep disorder group was lower than that of the control group(P<0.05). (5) Sleep disorder was negatively correlated with FSH and LH, and positively correlated with E2 (P<0.05). Conclusion: Sleep disorders may reduce the drive of the hypothalamic-pituitary-ovarian axis, resulting in slow FSH release, prolonged menstrual cycle, decreased luteal function, and increased transmission rates of non-conception or second ectopic pregnancy. [ABSTRACT FROM AUTHOR]

PCOS is a common endocrinopathy among premenopausal women, characterized by hyperandrogenism, anovulation, hirsutism. We evaluated credence of noscapine; in RU486 induced PCOS rat and compared with flutamide, a conventional drug. For 13 days, an oral dose of RU486 [20 mg/kg/day] was administered to Wistar rats exhibiting regular estrous cycle. Varying dosage of noscapine was given to PCOS rats and compared with rats administered flutamide. Cytology of estrous cycle and serum hormone levels (LH, FSH, PRL, estradiol, and testosterone) were measured. Histomorpho-metrical changes, events of apoptosis in theca and granulosa cells were observed using flow cytometry and the mode of cellular death was examined by TUNEL staining. Our findings suggested, normal folliculogenesis in PCOS rats, post noscapine administration (120 mg/kg) in 3-4 days with normal hormonal profile. Theca and granulosa cells undergo massive and marginal cellular degeneration respectively with no G2/M arrest. TUNEL staining confirms the granulosa cells in follicles are major cell type undergo apoptosis in RU486 administered rats. However, low apoptotic DNA fragmentations were found in theca cells. We conclude that the RU486 model is suitable for studies of the metabolic features of PCOS and noscapine appears to be promising therapeutic modality for amelioration of PCOS induced condition. [ABSTRACT FROM AUTHOR]

Ovulatory disorders are the most common clinical feature exhibited among obese women. Initiation of ovulation physiologically requires a surge of gonadotropin-releasing hormone (GnRH) released from GnRH neurons located in the hypothalamus. These GnRH neurons receive metabolic signals from circulation and vicinal neurons to regulate GnRH release. Leptin acts indirectly on GnRH via adjacent leptin receptor (LEPR)-expressing neurons such as proopiomelanocortin (POMC), neuropeptide Y (NPY)/agouti-related peptide (AgRP), and neuronal nitric oxide (NO) synthase (nNOS) neurons to affect GnRH neuronal activities. Additionally, hypothalamic inflammation also affects ovulation independent of obesity. Therefore, this review focuses on hypothalamic mechanisms that underlie the disturbance of hypothalamic–pituitary–ovarian (HPO) axis during obesity with an attempt to promote future studies and/or novel therapeutic strategies for ovulatory disorders in obesity. Obese female mice models demonstrate that obesity-causing ovulatory disorders are mainly for neuroendocrine dysfunction of hypothalamic–pituitary–ovarian (HPO) axis. Hypothalamus is the center of energy homeostasis and reproduction. The proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) and agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons in arcuate nucleus (ARC) regulating energy metabolism interplay with gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Kisspeptin neurons act as a mediator between energy metabolism and the reproductive system. Leptin acts on kisspeptin neurons indirectly through POMC/CART and AgRP/NPY neurons to affect energy metabolism and GnRH release. The nitric oxide (NO) signaling pathway is involved in reproduction and energy balance. The kisspeptin–receptor of kisspeptin (Kiss1r) pathway activated by estradiol stimulates the phosphorylation of neuronal NO synthase (nNOS) protein and switches surge-mode release of GnRH and promotes ovulation. Leptin resistance in hypothalamus caused by diet-induced obesity (DIO) hampers the treatment of obesity with leptin. Hypothalamic inflammation induced by high-fat diet (HFD) is regarded as a potential pathophysiological mechanism of obesity and dysfunction of the HPO axis. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals (EDCs) are the exogenous contaminants carrying the ability to disrupt the natural course of hormone action by mimicking or antagonizing their effects, altering their availability and levels of hormone receptors. Several studies have demonstrated a volley of female reproductive disorders, including early puberty, premature ovarian failure, anovulation and infertility. Recent evidence from studies in mammalian and sub-mammalian models has shown the involvement of epigenomics, bridging the gap between environmental exposure and genetic impacts, in negative influence of EDCs on physiological events. The oocyte epigenome interacts with environmental stressors encountered during the critical windows of development, namely prenatal, early childhood and puberty, wherein the deleterious impacts of EDCs get amplified, followed by its multi- and trans-generational inheritance. While it provides the reader with a background for epigenetics, the present overview summarizes the epigenetic signatures induced by EDCs. It describes the varied EDC-induced epigenetic alterations encountered in the female reproductive system and their physiological relevance in reproduction and development. More importantly, the underlying mechanisms governing the EDC-induced alteration in epigenetic marks, emphasising estrogen receptor modulation and its impact on various female reproductive organs, reveal the role of germlines as carriers of epimutations across generations. [ABSTRACT FROM AUTHOR]

Chronic viral hepatitis (CVH) is more than 70% of the total number of children with chronic hepatitis, and in the population - 0.5%. Adolescents are the most vulnerable group of the population due to the physiological and psychological characteristics of this age. The liver coordinates both adaptive and reproductive processes in the body, and during puberty is the formation of pituitary-gonadal relationships. The aim: to study the features of hormonal homeostasis in adolescent girls with CVH. Materials and methods. We examined 300 girls aged 12-17 years, of which 120 patients with CVH (60 patients with hepatitis B and 60 - with hepatitis C) and 180 relatively healthy patients with physiological sexual development. The diagnosis of CVH was established on the basis of medical history, clinical, virological, biochemical, morphological and instrumental examination. Results. Analysis of the obtained data of the functional state of the liver in the examined patients with CVH revealed disorders of the morphofunctional state of the liver, manifested by cytolysis syndrome, cholestasis, hepatocellular insufficiency and mesenchymal-inflammatory syndrome. In patients with CVH there was a decrease in the production of luteinizing hormone (4.35 ± 0.09 vs. 5.13 ± 0.08 mIU / ml, p

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

This study aimed to explore the regulating effect of Gegen Decoction(GGD) on the hypothalamic-pituitary-ovarian axis(HPOA) dysfunction in the mouse model of primary dysmenorrhea(PD). The mouse model of PD with periodic characteristics was established by administration of estradiol benzoate and oxytocin. Mice were randomized into control, model, GGD, and ibuprofen groups. The writhing response, hypothalamus index, pituitary index, ovary index, and uterus index were observed and determined. The serum levels of prostaglandin F&#95;(2α)(PGF&#95;(2α)), gonadotropin-releasing hormone(GnRH), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and estrogen(E&#95;2) levels were measured by ELISA kits. Western blot and qPCR were employed to determine the protein and mRNA levels, respectively, of gonadotropin-releasing hormone receptor(GnRH-R) in the pituitary tissue, follicle-stimulating hormone receptor(FSHR) and luteinizing hormone receptor(LHR) in the ovarian tissue, and estrogen receptor(ER) in the uterine tissue. The results showed that the writhing response, serum levels of PGF&#95;(2α), GnRH, FSH, LH, and E&#95;2, ovarian and uterine indexes, the protein and mRNA levels of GnRH-R in the pituitary tissue, FSHR and LHR in the ovarian tissue, and ER in the uterine tissue were significantly increased in the model group compared with those in the control group. GGD inhibited the writhing response, reduced the serum levels of PGF&#95;(2α), GnRH, FSH, LH, and E&#95;2, decreased the ovarian and uterine indexes, and down-regulated the protein and mRNA levels of GnRH-R in the pituitary tissue, FSHR and LHR in the ovarian tissue, and ER in the uterine tissue. The data suggested that GGD can regulate the HPOA and inhibit E&#95;2 generation in the mice experiencing recurrent PD by down-regulating the expression of proteins and genes related to HPOA axis, thus exerting the therapeutic effect on PD.

Objective: 7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. Methods: For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro, the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. Results: Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. Conclusions: These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women.

In contrast, POI cases with no detectable FSH/LH receptor mutations show a deficit in ovarian follicles. Keywords: female infertility; age-related decline in fertility; reproductive aging; hypothalamic-pituitary-ovarian axis; primary ovarian insufficiency (POI); ovarian biology EN female infertility age-related decline in fertility reproductive aging hypothalamic-pituitary-ovarian axis primary ovarian insufficiency (POI) ovarian biology 1 3 3 03/14/22 20220309 NES 220309 Introduction Worldwide, infertility affects between 8 and 12% of reproductive-aged couples ([8]). Clinical presentations of POI can also be due to FSH/LH receptor mutations leading to "resistant ovaries" retaining normal follicles in otherwise normal ovaries. [Extracted from the article]

Abstract Background This study aimed to detect changes in hormone levels in the hypothalamic–pituitary–ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic–pituitary–ovarian axis and reproductive function regulated by thyroid hormones was also investigated. Methods Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. Results The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic–pituitary–ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). Conclusions Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant–like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

The female reproductive system is strongly influenced by nutrition and energy balance. It is well known that food restriction or energy depletion can induce suppression of reproductive processes, while overnutrition is associated with reproductive dysfunction. However, the intricate mechanisms through which nutritional inputs and metabolic health are integrated into the coordination of reproduction are still being defined. In this review, we describe evidence for essential contributions by hormones that are responsive to food intake or fuel stores. Key metabolic hormones-including insulin, the incretins (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1), growth hormone, ghrelin, leptin, and adiponectin-signal throughout the hypothalamic-pituitary-gonadal axis to support or suppress reproduction. We synthesize current knowledge on how these multifaceted hormones interact with the brain, pituitary, and ovaries to regulate functioning of the female reproductive system, incorporating in vitro and in vivo data from animal models and humans. Metabolic hormones are involved in orchestrating reproductive processes in healthy states, but some also play a significant role in the pathophysiology or treatment strategies of female reproductive disorders. Further understanding of the complex interrelationships between metabolic health and female reproductive function has important implications for improving women's health overall., (© 2024 The Author(s).)

The hypothalamic-pituitary-ovarian (HPO) axis is a tightly regulated system controlling female reproduction. HPO axis dysfunction leading to ovulation disorders can be classified into three categories defined by the World Health Organization (WHO). Group I ovulation disorders involve hypothalamic failure characterized as hypogonadotropic hypogonadism. Group II disorders display a eugonadal state commonly associated with a wide range of endocrinopathies. Finally, group III constitutes hypergonadotropic hypogonadism secondary to depleted ovarian function. Optimal evaluation and management of these disorders is based on a careful analysis tailored to each patient. This article reviews ovulation disorders based on pathophysiologic mechanisms, evaluation principles, and currently available management options.

Anti-Müllerian hormone (AMH) is produced and secreted by granulosa cells of growing follicles, and its main role is to inhibit the recruitment of primordial follicles, reduce the sensitivity of follicles to follicle-stimulating hormone (FSH), and regulate FSH-dependent preantral follicle growth. It has become an effective indicator of ovarian reserve in clinical practice. Research on AMH and its receptors in recent years has led to a better understanding of its role in breast cancer. AMH specifically binds to anti-Müllerian hormone receptor II (AMHRII) to activate downstream pathways and regulate gene transcription. Since AMHRII is expressed in breast cancer cells and triggers apoptosis, AMH/AMHRII may play an important role in the occurrence, treatment, and prognosis of breast cancer, which needs further research. The AMH level is a potent predictor of ovarian function after chemotherapy in premenopausal breast cancer patients older than 35 years, either for ovarian function injury or ovarian function recovery. Moreover, AMHRII has the potential to be a new marker for the molecular typing of breast cancer and a new target for breast cancer treatment, which may be a link in the downstream pathway after TP53 mutation.

Abstract: Cytokines present in the reproductive system play an important role both in the modulation of immune responses to infectious challenge and in the establishment and maintenance of pregnancy. Interleukin 18 (IL-18) has been regarded as an important regulator of innate and acquired immune response, but its expression and distribution in the hypothalamic–pituitary–ovarian axis remain unclear. In this paper, the expression and distribution of IL-18 in non-pregnant, pregnant, and early abortive rats were examined using an ultra-sensitive immunohistochemical streptavidin–peroxidase method, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. The results showed that IL-18 expression in the pituitary, in follicular ovaries, and in the corpus luteum of abortive rats were significantly lower than that of pregnant and non-pregnant rats. However, the staining of IL-18 in the hypothalamus, interstitial glands of the ovary, and uterus of abortive rats was strikingly stronger than those of the non-pregnant ones. IL-18 mRNA expression in rat uterus was detected in all groups, whereas IL-18 mRNA content in abortive rat uterus was significantly higher than in normal pregnant rats. Further, IL-18 in the peripheral blood serum of abortive rats was significantly lower than in same-period normal pregnant rats. The differential expression of IL-18 in early abortion suggests that IL-18 may be related to the underlying mechanisms of abortion. [Copyright &y& Elsevier]

Menstruation is the cyclic, orderly sloughing of the uterine lining on account of the interactions of hormones produced by the hypothalamus, pituitary, and ovaries. There is a tendency among parents and clinicians to view oligo-amenorrhea as a normal variant in the teen years. In fact, the 95th percentile for the time interval between cycles is 90 days. Thus, it is abnormal for an adolescent to be amenorrheic for greater than 3 months, even in the early gynecologic years. Identification of abnormal menstrual patterns throughout adolescence may permit early identification of potential health concerns for adulthood. Few problems in gynecologic endocrinology are as complex or challenging to the clinician as amenorrhea. However, thorough evaluation of menstrual cycle disorders in adolescence provides a window of opportunity for early diagnosis and treatment of conditions affecting the hypothalamic-pituitary-ovarian (HPO) axis. Here we discuss a systematic approach to the evaluation and treatment of amenorrhea in adolescents who do not have androgen excess. There is strong evidence that estrogen deficiency is a risk factor for later development of osteoporosis and hip fracture. Delay in the evaluation and treatment of disordered menses in some cases may contribute to reduced bone density. Both patients and clinicians need to view the ovary as an important endocrine organ that helps maintain health, especially bone health. [ABSTRACT FROM AUTHOR]

Abstract: Structure–activity relationship studies are described, which led to the discovery of novel selective estrogen receptor modulators (SERMs) for the potential treatment of uterine fibroids. The SAR studies focused on limiting brain exposure and were guided by computational properties. Compounds with limited impact on the HPO axis were selected using serum estrogen levels as a biomarker for ovarian stimulation. [Copyright &y& Elsevier]

Two independent groups recently published data comparing pulsatile luteinizing hormone (LH) release between depressed and control women. Despite similar populations and LH sampling frequency, they reached different conclusions: Meller et al. [Am. J. Psych. 154 (1997) 1454] found disruption of normal LH pulsatility in depressed women, whereas Young et al. [Arch. Gen. Psych. 57 (2000) 1157] did not. To resolve this discrepancy, the current study applies a single, well-established statistical method, spectral analysis, to the two data sets and concludes that both depressed populations display significantly altered LH pulsatile release. [Copyright &y& Elsevier]

Zihuai recipe (ZHR), a Chinese herbal prescription, is widely used for the clinical treatment of Diminished ovarian reserve (DOR) infertility. However, little is known regarding its underlying mechanisms of DOR treatment. This study aimed to investigate the beneficial effects of ZHR on the treatment of DOR and to reveal the underlying mechanisms. S ixty female 8-week-old Sprague–Dawley rats were randomly divided into the following six groups (n =10 per group): control, DOR, low-dose(2.7 g/kg/day) ZHR (L-ZHR), medium-dose(5.4 g/kg/day), ZHR (M-ZHR), high-dose(10.8 g/kg/day) ZHR (H-ZHR), and hormone replacement therapy (HRT) treatment groups. The DOR model was established in all the groups, except the control group, by a single intraperitoneal injection of 90 mg/kg cyclophosphamide. After the induction of the DOR model, rats were weighed and administered either the relevant dose of ZHR or an equal volume of saline solution (in the control and DOR groups). Rats in the HRT group received estradiol valerate tablets (0.16 mg/kg/day), and with medroxyprogesterone acetate tablets (0.86 mg/kg/day) added on day 4. After 32 days of treatment, the rats were euthanized and the ovaries were collected for sampling. Ovarian morphology was observed by hematoxylin and eosin staining and the number of follicles was counted under a microscope. The serum levels of anti-Müllerian hormone (AMH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were quantified by ELISA. A TUNEL assay was used to analyze the level of apoptosis of the ovarian cells. The protein expressions of p-PI3K, p-AKT, PI3K, AKT, cleaved caspase-3, BAX, and Bcl-2 were measured by western blotting and immunohistochemistry. Data analysis was performed with SPSS 20.0 software. ZHR administration increased the ovarian index and the serum levels of AMH, GnRH, and E2, while lowering those of FSH and LH. ZHR treatment also increased the number of primordial, primary, secondary, and antral follicles, as well as the number of corpora lutea, but decreased the number of atretic follicles. Furthermore, ZHR administration decreased the percentage of TUNEL-positive ovarian cells. After treatment with ZHR, the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, cleaved caspase-3 and BAX were decreased, whereas the level of Bcl-2 was increased. ZHR improved the ovarian reserve in CTX-induced DOR rats. The mechanisms of ZHR on DOR may be mediated through the regulation of gonadal hormones of the hypothalamic-pituitary-ovarian axis (HPOA), and the inhibition of PI3K/AKT-mediated apoptosis in granulosa cells. The protective effects of ZHR on the ovaries of CTX-induced DOR rats were associated with the regulation of gonadal hormones in the hypothalamic-pituitary-ovarian axis (HPOA), and the suppression of PI3K/AKT-mediated apoptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant–like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women. [ABSTRACT FROM AUTHOR]

Objective: To find effective therapeutic approach for treating true idiopathic precocious puberty suitable to our national condition and different from gonadotrophin releasing hormone analogue. Methods: One hundred and six girls with idiopathic precocious puberty were divided into 3 groups. The 51 girls in the TCM-WM group were treated with Chinese herbal medicine combined with megestrol acetate (MA), 35 girls in the MA group treated with megestrol acetate alone, and 20 girls were taken as control group and given no treatment at all. Luteinizing hormone releasing hormone (LHRH) stimulating test were performed before and after treatment, and the size of the uterus and ovary, linear growth rate, X-ray bone age measurement and final height prediction were also observed simultaneously. Results: After treated with TCM-WM for 2.7 years in average, the luteinizing hormone (LH) peak value of LHRH stimulating test was reduced from 48.5 ± 5.2 IU/L to 12. 2 ± 1.3 IU/L, size of uterus and ovary decreased, secondary sexual characteristics regressed, the bone age difference/chronological age difference value (ΔBA/ΔCA) reduced from 1.35 ± 0.09 to 0.65 ± 0.05 and predictive final height increased from 153.3 ± 0.5 cm to 158.5 ± 0.6 cm. Conclusion: TCM-WM therapy could not only modulate the function of hypothalamic-pituitary-ovarian axis and the development of internal genitalia, but also could decelerate skeletal growth, delay skeletal maturation, and thereby prevent premature epiphyseal fusion and increase the final height of patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Design: Blood samples were obtained from 62 women. Results: When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. Conclusion: A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. Implications: This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. [Copyright &y& Elsevier]

Background and Objective: Premature ovarian failure is a worldwide concern effecting 1% of females of reproductive age. The objective of the present study was to analyze the role of inhibin alpha (INHα) gene mutation (769G>A) in patients with premature ovarian failure (POF) in the local population. Methods: This case-control association studywas conducted in Department of Gynecology, Jinnah Hospital and The Children's Hospital and Institute of Child Health from July 2015-July 2016. A total of n = 100 were recruited for this study and divided into two gropus females with equal number (n = 50)of patients andnormal controls of reproductive age (14 - 40 years). The screening of theINHα for 769G>A variation in exon 2 was done through DNA sequencing. Results: A higher frequency of the major allele G was seen in both the patients (99%) and the controls (87%) while comparing to minor allele A (1% in patients and 13% in controls). None of the patients was found to be homozygous (AA = 0%) for allele A, whereas, four of the controls were homozygous (AA = 8%). The frequency of the minor A allele in controls was found to be statistically significant (P-value = 0.002). Conclusion: An association of decreased risk of POFwith A allele of the 769G>A variant rather than increasing the risk of development of ovarian failure. [ABSTRACT FROM AUTHOR]

At present, glyphosate (GLP) is the most produced and used herbicide in the world. With the large-scale use of glyphosate-based herbicides (GBHs), their toxic effects on animals and plants have increasingly become a concern. Based on the Codex Alimentarius Commission (CODEX) dose (20 mg kg−1) and the dose set by the government (40 mg kg−1), four experimental groups in which Roundup® (R) herbicide was added to the feed of weaned piglets at GLP concentrations of 0, 10, 20, and 40 mg kg−1 were designed. The results showed that R had no significant effect on the vulvar size or index of reproductive organs but that it could affect the tissue morphology and ultrastructure of the uterus and ovary. With the increase in GLP concentration, the activities of antioxidant enzymes [SOD (P < 0.05) and GPx (P = 0.002)] in the uterus showed significant increases. Compared with the control group, the content of hydrogen peroxide (H 2 O 2) in the treatment groups increased significantly (P < 0.05), the malondialdehyde (MDA) content in the 10 mg kg−1 treatment group was significantly higher than that in the control group. We measured hypothalamic-pituitary-ovarian axis (HPOA) hormones and also found that GLP significantly increased luteinizing hormone-releasing hormone (LHRH), gonadotropin-releasing hormone (GnRH) and testosterone (T) content (P < 0.05) and decreased follicle-stimulating hormone (FSH) content (P < 0.05). In summary, although R does not affect the vulvar size or reproductive organ index of weaned piglets, it changes the morphology and ultrastructure of the uterus and ovaries, interferes with the synthesis and secretion of HPOA hormones, and causes changes in the balance of the antioxidant system of uterus. This study provided a theoretical basis for preventing reproductive system harm caused by GBHs. Image 1 • Glyphosate (GLP) has been detected in a variety of food crops and surface water. • The dose of GLP was designed according to the concentration of 20 mg kg-1 by CODEX and 40 mg kg-1 by the government. • The study on the reproductive toxicity of GLP to female weaned piglets is unprecedented. • GLP had no effect on reproductive organ index and vulva of female weaned piglets. • GLP affects the development of reproductive organs by interfering with the synthesis and secretion of HPOA hormones. [ABSTRACT FROM AUTHOR]

7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro , the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women. Image 1 • 7,8-DHF improves hypothalamic-pituitary-ovarian axis function in mature adult female mice. • 7,8-DHF protects against ovarian failure and onset of earlier menopause. • 7,8-DHF-induced transactivation of ERα is crucial to activate BDNF/TrkB signaling cascades. • 7,8-DHF-induced activations of ERα and BDNF/TrkB signaling are interdependent. • Src family kinases play a core role in the crosstalk of ERα and BDNF/TrkB signaling pathways. [ABSTRACT FROM AUTHOR]