Hypothalamic-pituitary-gonadal Axis Research Articles

Acute Exposure to Ozone Affects Circulating Estradiol Levels and Gonadotropin Gene Expression in Female Mice

Ozone, a critical air pollutant, has been shown to lead to systemic inflammation that can alter bodily functions, including hormone secretion, fertility, and the hypothalamic–pituitary–gonadal (HPG) axis. This study aimed to quantify changes in hormone production and follicle development after acute exposure to ozone using an animal model to identify the potential mechanisms underlying the observed effects of air pollution exposures on fertility and hormone secretion. To accomplish this, regularly cycling 8-week-old female C57BL/6J mice were exposed to 2 ppm of ozone or filtered air (control) for 3 h on the day of proestrus. Blood, ovaries, brain tissues, and pituitary glands were collected at 4 h after exposure to evaluate hormone levels, ovarian follicle distribution, and gene expression. Ovaries were also harvested at 24 h post-exposure. We found that at 4 h after ozone exposure, mice had significantly higher (30%) circulating estradiol levels than mice exposed to filtered air. This effect was accompanied by a decrease in mRNA expression of gonadotropin genes (LH, FSH) and gonadotropin-releasing hormone in the pituitary gland. Analysis of ovarian tissue at 4 h and 24 h after exposure showed no significant changes in follicle composition or the expression of steroidogenesis genes. We conclude that acute ozone exposure affects sex hormone levels and disrupts the HPG axis. Future studies addressing chronic or long-term effects of air pollution exposure are needed to elucidate the mechanisms by which ambient ozone affects endocrine function.

Phoenixin's Influence on HPG Axis and Inflammation in Elite Ice Hockey Athletes: A Cross-Sectional Analysis.

The neuropeptide phoenixin (PNX) may be involved in regulating the hypothalamic-pituitary-gonadal (HPG) axis and inflammatory responses. This study aims to investigate the role of PNX in the regulation of HPG axis function in ice hockey players and its impact on body composition. This cross-sectional study included 65 male ice hockey players aged 18-22, divided into untrained, non-elite athlete, and elite athlete groups. Body composition was assessed using bioelectrical impedance analysis, and plasma levels of PNX, gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), testosterone, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay. Elite ice hockey players exhibited significantly higher lower limb and core skeletal muscle mass, skeletal muscle index, and testosterone levels, aligning with the high-intensity intermittent nature of hockey training. Compared to the non-training group, ice hockey training groups showed elevated levels of PNX, GnRH, testosterone, and TNF-α, along with reduced levels of LH and IL-6. PNX concentration positively correlated with lean body mass, skeletal muscle mass, skeletal muscle index, serum GnRH, and testosterone levels, and negatively correlated with serum LH and IL-6 levels. In conclusion, PNX may enhance skeletal muscle mass in ice hockey players, particularly in the lower limbs and core muscles, by promoting HPG axis activity while inhibiting inflammatory responses and reducing HPG axis suppression. These findings provide new insights into the physiological adaptation mechanisms of ice hockey players, potentially aiding in the optimization of training strategies and improvement of athletic performance.

Immunization with OPN5 increased seasonal degradation of reproductive activity in Magang ganders.

To investigate the regulatory mechanism mediated by hypothalamic OPN5 on seasonal changes in the reproductive activities of domestic geese, 60 Magang ganders in their breeding period were selected for the experiment and evenly divided into an immunization group(OPN5-IM) and a control group. On days 0, 15 and 30, ganders in the immunized group were immunized with OPN5-KLH protein vaccine, and ganders in the control were immunized with the same amount of blank emulsified vaccine. Additionally, 120 female geese were provided to stimulate the reproductive activities of male geese. The results showed that the arrangement of spermatogenic cells was disturbed, the number of sperm decreased, and the testicular weight, seminiferous tubule area, length diameter, spermatogenic epithelium thickness decreased significantly with the natural day length prolonged. Moreover, the concentration of testosterone and LH decreased significantly while PRL increased. The prolonged photoperiod significantly affected the gene expression of GnRH-I, VIP, FSHβ, FSHR, LHβ, PRL, and PRLR in ganders. Specifically, the gene expression of GnRH-I, FSHβ, and LHβ in the hypothalamus and pituitary decreased, while the gene expression of VIP, PRL, and PRLR increased. Following OPN5 immunization, the anti-OPN5 antibody titer of ganders in the OPN5-IM group was notably higher than in the control group. The testicular degeneration was severe in OPN5-IM group compared with the control, as evidenced by a significant reduction in seminiferous tubule area, length diameter, and thickness of spermatogenic epithelium in the immunized group on day 60. Additionally, the concentrations of testosterone and LH were lower in the OPN5-IM group than in the control group, whereas PRL was higher. Moreover, OPN5 immunization significantly affected the expression of GnRH-I, PRL, and PRLR. OPN5 mRNA and protein expression were higher in the immunized group, whereas TRH, DIO2, and TSHR mRNA expressions were lower. However, DIO3 mRNA and protein were up-regulated in the immunized group. In conclusion, our results indicated that the reproductive performance of Magang geese degraded from the breeding to the non-breeding period as daylight was extended. Immunization against OPN5 increased OPN5 expression and down-regulated the TSH-DIO2/DIO3 pathway, further to affect the HPG axis and accelerate the degradation of reproductive activity. Therefore, OPN5 may play an important mediating role in light-regulating seasonal reproductive degradation in Magang geese.

Polystyrene microplastics exacerbate acetochlor-induced reproductive toxicity and transgenerational effects in zebrafish.

Microplastic (MPs) can adsorb co-existing pollutants, and alter their behavior and toxicity. Meanwhile, amide herbicides like acetochlor (ACT) are widely used in agriculture, with potential endocrine-disrupting effects that raise ecological concerns. The aim of this research was to examine the effects of MPs on the reproductive endocrine disruption caused by ACT and the effects of maternal transmission. Zebrafish were employed in this study to assess the reproductive toxicity of ACT alone and in combination with polystyrene microplastics (PS-MPs) of different sizes (200 nm and 2 μm) and concentrations (0.1 and 1 mg/L) over a 63-day exposure experiment. The results indicated that ACT was concentrated in zebrafish tissues in the order: intestine > liver > gill > brain > gonad > muscle. PS-MPs increased ACT bioaccumulation, worsened gonadal damage, led to abnormalities in hormone levels, and caused disruptions in HPG axis gene expression, further exacerbating the reproductive toxicity. Maternal transfer of ACT affected offspring growth, thyroid function, and HPT axis gene expression, with nanoplastics (NPS) amplifying these adverse effects. This study offers crucial insights into the ecological hazards posed by ACT and PS-MPs, emphasizing the increased toxicity due to PS-MPs.

Associations of fetal and infant growth with pubertal timing

ObjectiveImpaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic–pituitary–gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and...

Assessment of the impact of HIV infection on the hypothalamic-pituitary-ovarian axis and pubertal development among adolescent girls at a tertiary centre in Zimbabwe: a cross-sectional study

BackgroundProper planning of reproductive health needs for HIV-infected adolescents requires a clear understanding of the effects of HIV infection on adolescents’ pubertal development.ObjectiveTo assess the effects of HIV infection on the hypothalamic-pituitary-ovarian (HPO) axis, ovarian reserve and pubertal development in adolescent girls at a tertiary hospital in Zimbabwe.MethodsThis was a cross-sectional survey of HIV-infected adolescent girls aged 10–19 years, with available CD4 + count results at a tertiary hospital in Zimbabwe. Consecutive sampling was used to select study participants. Pubertal milestones were assessed using the age of menarche and Tanner stage for breast and pubic hair development. Growth was assessed using World Health Organisation growth charts. The HPO axis was evaluated by measuring serum follicular stimulating hormone (FSH), luteinising hormone (LH) and estradiol. The ovarian reserve was assessed in adolescents above 18 years of age by measuring the serum anti-mullein hormone (AMH) levels. Data were analysed in STATA version 13.0, and the results are presented as mean (SD) or median (quartiles) and proportions, as appropriate.ResultsOne hundred and one (101) HIV-infected adolescents were recruited for the study. Menarche, thelarche and pubarche were delayed in 15.9%, 28.6% and 46.8% of the adolescents, respectively. A total of 59.4% had moderate to severe stunting, and 53.5% were either overweight or obese. Most participants had normal serum FSH, LH, and estradiol levels, and there was no association between these hormone levels and growth indicators. The serum AMH levels were reduced in 24.1% of the adolescents. There were no significant differences in the hormonal levels and pubertal development between the WHO CD4 classes.ConclusionHIV infection is associated with stunted growth and delayed sexual maturation with an intact HPO axis in the majority of adolescents. There was no association between growth indicators and FSH and LH levels. The degree of HIV immunosuppression had no significant impact on the HPO axis and pubertal development. A larger study is needed to assess the impact of HIV infection on ovarian reserve.Trial registration: This protocol was approved by the Medical Research Council of Zimbabwe (MRCZ) (reference number MRCZ/A/1730).

Best practices for including sex as a variable in appetite research.

Despite increasing recognition that sex is a critical variable in appetite research, many studies fail to include participants of both sexes, fail to consider reproductive physiology in participant selection, or include both sexes but fail to test for sex differences in outcomes. To help remedy this situation, this article seeks to engender enthusiasm for including sex as a variable in appetite research. We first illustrate some sex differences in healthy and disordered eating, including both male-female differences and differences across the menstrual cycle. We next provide methodological guidance for studies involving male and female participants around puberty, during reproductive adulthood, and during reproductive senescence. Studies in children ≥5y of age should consider adrenarche and gonadarche. Appetite studies in girls and women following menarche and similarly aged males should consider the influences of sex-specific aspects the hypothalamic-pituitary-gonadal (HPG) axis function. The cyclicity of HPG function (i.e., the menstrual cycle) in girls and women presents the challenge of identifying of menstrual-cycle subphases, which are highly variable within and between individuals. Reproductive senescence refers to changes in HPG axis function that occur in both men and women beginning in mid-life. Current best practices involve consideration of hormone-assay methodology, experimental design, and statistical analyses. On the horizon are options based on wearable-sensors and nanotechnology. Well informed consideration of sex as a variable will accelerate progress in appetite research by increasing rigor, replicability, and relevance.

GnIH secreted by green light exposure, regulates bone mass through the activation of Gpr147

Reproductive hormones associated with the hypothalamic-pituitary-gonadal (HPG) axis are closely linked to bone homeostasis. In this study, we demonstrate that Gonadotropin inhibitory hormone (GnIH, one of the key reproductive hormones upstream of the HPG axis) plays an indispensable role in regulating bone homeostasis and maintaining bone mass. We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density (BMD) in mice primarily by enhancement of osteoclast activation in vivo and in vitro. Mechanistically, GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT, MAPK, NF-κB and Nfatc1 signaling pathways. Furthermore, GnIH treatment was able to alleviate bone loss in aging, ovariectomy (OVX) or LPS-induced mice. Moreover, the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss. In humans, serum GnIH increases and bone resorption markers decrease after green light exposure. Therefore, our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.

Clinician's guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids.

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.

Insights into the toxic impact of long-term exposure to diethyl phthalate on commercially important species Catla (Labeo catla)

BackgroundDiethyl phthalate (DEP), used as a plasticizer, is more prevalent in the aquatic environment due to its widespread usage in plastics, cosmetics, and numerous pharmaceutical industries. It is a potential endocrine disruptor, but the underlying mechanism in fish needs to be investigated. The present study evaluated the toxic impacts of DEP exposure for 30 days on commercially important fish Labeo catla (Catla). Alterations at multiple level endpoints of the hypothalamic–pituitary–gonadal axis (HPG axis) were assessed. DEP-induced changes in oxidative stress, histopathological changes (liver, kidney and brain) and bioaccumulation in fish muscle were also evaluated.ResultsDEP exposure to 1/10th (1.62 mg/L) and 1/50th (0.32 mg/L) LC50 dose for 30 days to Catla revealed that it stimulated the expression of kisspeptin (Kiss 1 and Kiss 2) genes in the hypothalamus, leading to an increased GnRH concentration (36.75%) in the higher dose. The brain FSH levels increased by 11.24 and 55.42% times than control in both the doses. This led to an increase in circulating sex steroids E2 (41.62%) and 11 KT (24.59%) and eventually triggered hepatic Vtg production (23.90%) in a dose-dependent manner. DEP exposure lowered the concentration of antioxidants superoxide dismutase (SOD) and catalase (CAT), the effect being more pronounced in the higher dose. The histopathological alterations, such as hepatocyte vacuolization, sinusoidal congestion, loss of brush border, degeneration of lumen, infiltration of eosinophilic cells in liver, kidney and brain, respectively, were noted.ConclusionsThis pioneering study could provide detailed insight into the endocrine disruptive potential of DEP in fish, as evidenced by its impact at multiple endpoints, even at low doses after 30 days of exposure. The output of this investigation thus emphasized the need for regular monitoring of DEP for ecological risk assessment.

Cholecystokinin (CCK) Is a Mediator Between Nutritional Intake and Gonadal Development in Teleosts.

Nutritional intake is closely linked to gonadal development, although the mechanisms by which food intake affects gonadal development are not fully understood. Cholecystokinin (CCK) is a satiety neuropeptide derived from the hypothalamus, and the present study observed that hypothalamic CCK expression is significantly influenced by food intake, which is mediated through blood glucose levels. Interestingly, CCK and its receptors were observed to exhibit a high expression in the hypothalamus-pituitary-gonad (HPG) axis of grass carp (Ctenopharyngodon idellus), suggesting that CCK is potentially involved in regulating fish reproduction through the HPG axis. Further investigations revealed that CCK could significantly stimulate the expression of gonadotropin-releasing hormone-3 (GnRH3) in the hypothalamus. In addition, single-cell RNA sequencing showed that cckrb was highly enriched in pituitary follicle-stimulating hormone (FSH) cells. Further study confirmed that CCK can significantly induce FSH synthesis and secretion in primary cultured pituitary cells. Additionally, with primary cultured ovary cells as a model, the in vitro experiment demonstrated that CCK directly induces the expression of lhr, fshr, and cyp19a1a mRNA. This indicates that hypothalamic CCK may act as a nutrient sensor involved in regulating gonadal development in teleosts.

Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis

Objective To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. Methods The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. Results Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 − 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD − 0.027; CI95% −0.227 − 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. Conclusions The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

Interaction between Vitamin D homeostasis, gut microbiota, and central precocious puberty.

Central precocious puberty (CPP) is an endocrine disease in children, characterized by rapid genital development and secondary sexual characteristics before the age of eight in girls and nine in boys. The premature activation of the hypothalamic-pituitary-gonadal axis (HPGA) limits the height of patients in adulthood and is associated with a higher risk of breast cancer. How to prevent and improve the prognosis of CPP is an important problem. Vitamin D receptor (VDR) is widely expressed in the reproductive system, participates in the synthesis and function of regulatory sex hormones, and affects the development and function of gonads. In addition, gut microbiota plays an important role in human health by mainly regulating metabolites, energy homeostasis, and hormone regulation. This review aims to clarify the effect of vitamin D deficiency on the occurrence and development of CPP and explore the role of gut microbiota in it. Although evidence on the interaction between vitamin D deficiency, gut microbiota, and sexual development remains limited, vitamin D supplementation and gut microbiota interventions offer a promising, non-invasive strategy for managing CPP.

Network analysis of the hair-based nine hormones from four neuroendocrine systems.

The stress response maintains the homeostasis of the body's internal environment and normal physiological activities, involving several neuroendocrine systems, such as the HPA axis, the HPG axis, the endocannabinoid system, and the melatonin system. However, studies on the intricate interactions among the four neuroendocrine systems are lacking, and it is not clear how these interactions are affected by demographic variables. The aim of this study was to investigate the network characteristics of hormonal networks comprising nine hormones from four neuroendocrine systems and how they were affected by demographic variables. 252 healthy current students were recruited from Southeast University, China. The concentrations of nine hormones in their hair were measured by LC/MS methods, and hormonal network was constructed. Network analysis was used to characterize the interrelationships between hormones or neuroendocrine systems, central hormones, bridge hormones, hormonal network characteristics, and their changes in response to demographic variables. Complex interactions between the HPA axis, the HPG axis, the ECS and the melatonin system formed a sparse and stable network, with cortisol and cortisone being the central hormones and melatonin as the bridge hormone. Demographic variables did not affect the overall characteristics of the network or the central hormone, but a number of specific connections in the network changed and the bridge hormones became cortisone and progesterone. The interactions between the four stress-related neuroendocrine systems were relatively stable and were centered and initiated by the HPA axis. Demographic variables did not affect the overall structure of the network, but influenced local features of the network, such as edge weights and bridge centrality.

Active immunization with a novel recombinant GnRH vaccine inhibits reproductive function in male goats.

Gonadotropin-releasing hormone (GnRH) vaccines have been widely used to effectively inhibit gonadal development and reproductive function. To improve the immunogenicity of GnRH, we developed and evaluated the effects of GnRH6-kisspeptin-CRM197 immunization on the reproductive function in male goats. Thirty 3-month-old male goats (n = 30) were randomly assigned to control, surgical, and immunized groups. The immunized group received a 2 mL injection of the GnRH6-kisspeptin-CRM197 with a booster administered four weeks later. The control group was administered a white oil adjuvant. Blood samples were collected at regular intervals, and at week 20, the animals were euthanized for tissue collection. Serum antibody titers and testosterone levels were measured using ELISA and CLIA, respectively. Testicular parameters and histology were evaluated. The mRNA levels of reproductive-related genes in the HPG axis were measured using RT-qPCR. The results showed that the immunized goats had significantly increased serum GnRH and kisspeptin antibodies (P < 0.05) but decreased testosterone concentrations (P < 0.05) compared to the control group. Testicular size and histology were significantly affected in the immunized group, with notable reductions in testicular weight and dimensions (P < 0.01), and evidence of vacuolar degeneration and suppressed sperm production. The mRNA levels of FSHβ and LHβ in the pituitary, as well as FSHR, LHR, 3βHSD, and 17βHSD in the testis, were significantly lower in the immunized group compared to controls (P < 0.05). These findings suggest that GnRH6-kisspeptin-CRM197 is a safe antigen and a promising immunocastration vaccine with enhanced efficacy.

Toxic effects of chronic exposure to BPAF and perturbation of gut microbiota homeostasis in marine medaka (Oryzias melastigma)

Bisphenol AF (BPAF), a substitute for bisphenol A (BPA), exhibits potent endocrine-disrupting properties that pose a serious health hazard to organisms. This study employed marine medaka as a model, subjecting them to different concentrations of BPAF (0.61, 6.65, and 91.88 μg/L) from the embryonic stage for a period of 160 days. Findings showed that 91.88 μg/L BPAF reduced survival rates and altered sex ratios. Furthermore, exposure to BPAF at all concentrations led to a significant increase in body length and weight. Behavioral analysis revealed that BPAF exposure impaired the swimming ability of the medaka. Histological changes included disrupted ovarian development, reduced sperm count, liver inflammation, and intestinal damage. Gene expression analysis revealed impacts on nervous system (e.g., gap43, itr, elavl3), HPG axis (e.g., gthα, erα, 3βhsd), and liver genes (e.g., chgl, vtg2). Additionally, BPAF altered the diversity and richness of gut microbes in marine medaka, leading to significant changes in specific bacterial species and intestinal functions. In conclusion, long-term BPAF exposure induced neurotoxicity, reproductive toxicity, and impaired digestive and immune systems in marine medaka, with sex-specific effects. These results provide further evidence of the potential hazards of BPAF as an environmental pollutant.

Sex-related hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axis adaptation during military training.

Reproductive endocrine function adapts to psychological, environmental, and energy-associated stressors. Multistressor environments upregulate hypothalamic-pituitary-adrenal (HPA) axis, causing suppression of the hypothalamic-pituitary-gonadal (HPG) axis, but it is not known if this pattern or its magnitude is sex biased. We compared HPG and HPA axis activity in 9 men and 34 women undergoing Army training. One-hour low-dose gonadorelin and Synacthen tests were conducted at 1 and 29 wk, measuring gonadotrophins and cortisol. Cortisol was measured from hair every 3 mo. Morning and evening salivary cortisol and psychometric questionnaires were measured at six timepoints. Sexes were compared over time by two-way ANOVA. Gonadotrophin responses were significantly higher in women than men in week 1, but no sex difference was seen at week 29 (no significant sex × time interaction). Week 1 cortisol response was higher among men, but week 29 cortisol response was higher among women (sex × time F(1,44) = 18.0, P < 0.001). Hair cortisol was higher among women than men beforehand, not different between sexes during the first 3 mo, and significantly higher among women during training months 5-11 (F(3,15) = 3.25, P = 0.024). Morning salivary cortisol was higher among women in weeks 8 and 14, but higher among men in week 29 (F(4,76) = 4.0, P = 0.005). No differences were seen in evening salivary cortisol. Psychometrics did not change or differ between sexes. HPA axis responses to military training were greater among women than men. HPG axis responses suggest greater downregulation among women. These findings will enable equitable and individualized management of people undergoing periods of intensive physical stress.NEW & NOTEWORTHY We conducted a comprehensive comparison of adrenal and reproductive function in men and women undergoing 11-mo military training. We found progressively elevated cortisol levels and dynamic cortisol response to stress among women, but not men, and suppression of reproductive function among women. The physiological impact of stressful military training was greater among women than men; this could not be explained by energy balance, and sex-specific effects of sleep, socio-ethnographic, or other stressors may be responsible.

Association between Metal(loid) Exposure and Risk of Polycystic Ovary Syndrome Mediated by Anti-Müllerian Hormone among Women Undergoing In Vitro Fertilization and Embryo Transfer

ObjectiveTo investigate the relationship and potential pathways between metal(loid) exposure and the risk of polycystic ovary syndrome (PCOS) in women of childbearing age. MethodsThis case-control study included 200 patients with PCOS (cases) and 896 non-PCOS controls with the age of 25–37 years. The concentrations of 29 metal(loid)s in the follicular fluid (FF) and clinical indicators in the serum were measured in all participants. Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid) exposure and PCOS risk and investigate the possible roles of clinical indicators, respectively. ResultsLogistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk (highest vs. lowest quartile: adjusted odds ratio = 2.94, 95% confidence interval: 1.83–4.72). A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone (AMH) were strongly associated with increased PCOS risk induced by high copper exposure. The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. ConclusionCopper may affect PCOS risk through the hypothalamic–pituitary–ovarian axis, mediated by AMH. Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

The antidepressant-like effects of kisspeptin-10 are reversed by kisspeptin antagonist peptide 234 in male rats.

Kisspeptins are reported to be the most potent activators of the hypothalamus-pituitary-gonadal (HPG) axis known to date. Kisspeptin potently elicits gonadotropin-releasing hormone (GnRH) release and luteinizing hormone (LH) secretion, even in the pre-pubertal period. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network primarily implicated in emotional behaviors alongside sexual functions. Therefore, an increasing body of studies has implicated kisspeptin as having many influences on emotional behaviors. The study was set out to explore if the kisspeptin/GPR54 signaling system is required for the anti-depressant-like effect of kisspeptin-10 (KP-10), besides the regulation of the HPG axis. To test this concept, peptide 234 (P234), a kisspeptin antagonist, was given to the male rats, and its modulatory effect on the anti-depressant-like effects of kisspeptin was investigated by using a forced swimming test (FST). The study has also sought to know whether kisspeptin can exert its effects through adrenergic and serotonergic receptors. To investigate this, the agents yohimbine (Yoh), an alpha-2 adrenergic receptor antagonist, and cyproheptadine (Cry), a non-selective 5-HT2 serotonergic receptor antagonist, were administered in the experiments. Our results indicate that, in rats, the anti-depressant-like effects of KP-10 in a modified rat FST are mediated by GPR54 receptors, since the kisspeptin antagonist peptide 234 reversed kisspeptin-induced anti-depressant-like effects. Our data also demonstrate that the anti-depressant-like effects of kisspeptin, at least in part, are mediated by an interaction of the alpha-2 adrenergic and 5-HT2 serotonergic receptors.

Expression profile of RFRP-3 gene in hypothalamic tissue and its relationship with reproductive hormones across phases of the estrous cycle in female rats

The expression profile of RFRP-3 during the different phases of the estrous cycle and its relationship with reproductive hormones were studied in 36 adult female Wister rats. Phases of the estrous cycle were characterized by visual observation of the vagina and vaginal exfoliated cell cytology. The expression profile of the RFRP-3 gene in the hypothalamic tissue was evaluated by real-time qPCR. Reproductive hormones (LH, FSH, estrogen, and progesterone) were measured from plasma by enzyme immunoassay. The expression level of RFRP-3 was significantly higher (P < 0.01) during diestrus compared to other phases of the estrous cycle. The lowest expression level was detected during estrus and metestrus. The highest level of LH was detected during the proestrus and metestrus and the lowest during the diestrus. Higher expression of RFRP 3 during diestrus is consistent with the higher level of estrogen, however, the lower expression of RFRP 3 during estrus and met estrus did not corroborate with the level of estrogen. The findings of this research work revealed significant up-regulation of RFRP-3 during the estrous cycle together with higher estrogen level. Therefore it can be concluded that higher expression of RFRP 3 may lead to the suppression of the HPG axis during diestrus in rats and estrogen may be involved in the regulation of RFRP-3.