Hypothalamic-pituitary-gonadal Axis Research Articles

Hypothalamic-pituitary-ovarian axis suppression is common among women during US Army Basic Combat Training

ObjectiveLess than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health...

Effects of whole life-cycle exposure to carbaryl on reproduction of female marine medaka (Oryzias melastigma) and their offspring

Carbaryl is widely used as a highly effective insecticide which harms the marine environment. This study aimed to assess the reproductive toxicity of chronic carbaryl exposure on female marine medaka and their female offspring. After a 180-day exposure from embryonic period to adulthood, females exhibited reduced attraction to males, decreased ovulation, increased gonadosomatic index and a higher proportion of mature and atretic follicles. These reproductive toxic effects of carbaryl may stem from changes in hormone levels and transcription levels of key genes along the HPG axis. Furthermore, maternal carbaryl exposure had detrimental effects on the offspring. F1 females showed the reproductive disorders similar to those observed in F0 females. The significant changes in the transcription levels of DNA methyltransferase and demethylase genes in the F0 and F1 generations of ovaries indicate changes in their DNA methylation levels. The changes in DNA methylation levels in F1 female marine medaka may lead to changes in the expression of certain reproductive key genes, such as an increase in the transcription level of cyp19a, which may be the reason for F1 reproductive toxicity. These findings indicate that maternal exposure may induce severe generational toxicity through alterations in DNA methylation levels. This study assesses the negative impacts of whole life-cycle carbaryl exposure on the reproductive and developmental processes of female marine medaka and its female offspring, while offering data to support the evaluation of the ecological risk posed by carbaryl in marine ecosystems.

Production of polyclonal anti-human follicle stimulating hormone (hFSH) in Balb/C mice for standardizing an immunoradiometric assay for hFSH

AbstractThis study aimed to produce polyclonal antibodies of human follicle-stimulating hormone (anti-hFSH) in order to establish an immunoradiometric assay (IRMA). The anti-hFSH was tested using the prepared 125I-hFSH tracer. The 125I-hFSH tracer was carried out using the lactoperoxidase method, resulting in a radiochemical yield of 87.6% and a specific activity of 136 μCi/μg. The anti-hFSH produced gave highest displacement percentages (80.3, 79.8 and 71.2%) and a successful immunoresponse. hFSH-IRMA system was developed using 125I-MoAb-hFSH tracer (DIA Source). The results show a precise, stable and accurate measurements of hFSH-IRMA with a sensitivity of 0.15 mIU/ml. The coefficient variation for intra-assay is less than ± 10% and for inter-assay, it is less than ± 15%. Additionally, the liner correlation coefficient r is equal to 0.999. This technique can be utilized as a helpful diagnostic tool to study fertility and diseases of the hypothalamus-pituitary–gonadal axis in humans.

Obesity and Male Fertility: An In-Depth Review of the Impact of Elevated BMI

This paper discusses the complex relationship between obesity and male infertility in a detailed manner. According to the introduction, obesity-related infertility is importantly discussed since it affects some 15% of couples in which half cases are attributed for obesity-related infertility is important to discuss since it affects some 15% of couples, and half of cases are attributed to male factors. The body of the analysis discusses various factors related to obesity-associated male reproduction implications, including endocrinopathies insulin sensitivity, sperm DNA fragmentation, erectile dysfunction OSAS asshened semen characteristics chronic epididymitis and epigenetic changes. The above discussion on endocrinopathies shows that excessive white adipose tissues derail the HPG axis, triggering hormonal imbalances which lead to infertility. This paper explains the interaction between insulin resistance and testosterone levels in type 2 diabetes affected men. The paper also focuses on sperm DNA fragmentation, showing the association between obesity and increased levels of sperm DNA damage, mitochondrial dysfunction and abnormality in morphology. Erectile dysfunction is focused on obesity-induced oxidative stress, inflammation and hormonal abnormalities that impair male reproductive function. Additionally, the role of sleep apnea in testosterone secretion and possible association between its severity to lower level of this hormone are presented. There is a further discussion of altered sperm traits, chronic epididymitis and epigenetic changes with regard to the obesity which gives us a broad perspective on male fertility. The paper then concludes its discussion regarding weight loss interventions restoring fertility, focusing on diet and exercise as means for reducing certain parameters associated with modifiable inflammatory markers linked to infertility. In summary, the general assessment highlights that obesity management is crucial in male infertility.

Intracerebroventricular injection of spexin stimulates the hypothalamic-pituitary-testicular axis and increases the secretion of male reproductive hormones in rats

BackgroundMale reproductive functions are regulated in the hypothalamic-pituitary-gonadal (HPG) axis. Any problem in this axis would lead to the deterioration of reproductive functions. The present study aimed to investigate the effects of intracerebroventricular (icv) Spexin (SPX) infusion on the HPG axis in detail. Methods40 Wistar albino rats were divided into four groups: control, sham, SPX 30 nmol and SPX 100 nmol (n=10). 30 nmol/1 µl/hour SPX was administered icv to the rats in the SPX 30 nmol group for 7 days, while rats in the SPX 100 nmol group were administered 100 nmol/1 µl/hour SPX. On the 7th day, the rats were decapitated, blood and tissue samples were collected. Serum LH, FSH and testosterone levels were determined with the ELISA method, GnRH mRNA expression level was determined in hypothalamus with the RT-PCR method. Seminiferous tubule diameter and epithelial thickness were determined with the hematoxylin-eosin staining method. ResultsSPX infusion was increased GnRH mRNA expression in the hypothalamus tissue independent of the dose (p<0.05). Serum LH, FSH and testosterone levels in the SPX groups were increased when compared to the control and sham groups independent of the dose (p <0.05). Histological analysis revealed that SPX infusion did not lead to any changes in seminiferous epithelial thickness, while the tubule diameter increased in the SPX groups (p<0.05). ConclusionThe study findings demonstrated that icv SPX infusion stimulated the HPG axis and increased the secretion of male reproductive hormones.

P-644 Effect of Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve on oocyte maturation: a Randomized controlled trial

Abstract Study question To define whether letrozole co-stimulation with gonadotropin in normal-ovarian reserve women will improve the number of oocyte maturation. Summary answer Letrozole co-stimulation in normal ovarian reserve resulted in a reduced number of MII. What is known already Letrozole functions as an aromatase inhibitor. By inhibiting this enzyme, letrozole effectively lowers estrogen levels. Thus, letrozole prevents the estrogen-negative feedback to the HPO axis, which can increase the secretion of gonadotropins from the pituitary gland to promote folliculogenesis. The application of letrozole co-stimulation in women with a normal ovarian reserve is still debated. Study design, size, duration This study is an open-labeled, randomized controlled trial. Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve. The RCT was conducted at the Fertility and Reproductive Biology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital in Thailand, from March 2023 to October 2023. Participants/materials, setting, methods One hundred forty-four infertile women 18-40 years old with normal ovarian reserve (AMH 1.2-7 ng/ml, AFC ≥ 5) were random to gonadotropin co-stimulation with letrozole 5 mg once daily (n = 72) and gonadotropin alone (n = 72). The number of MII oocytes, follicle-to-oocyte index, GDF-9 and BMP-15 in follicular fluid were assessed. Main results and the role of chance Letrozole co-stimulation resulted in a significantly reduced number of MII [8 (4,12) vs 9 (5, 15.8), p = 0.042] and the rate of MII [ 71.7(60, 83.8) vs 80 (66.7, 90), p = 0.013]. However, the number of retrieved oocytes [12 (6,16.8) vs. 12 (6,16), p = 0.335] and FOI [85.7 (57.4,107.5) vs 84.2 [61.8, 112.5], p = 0.396] remained unchanged. The total dose of gonadotropin in the letrozole group was no different from the control group [1,350 (1,200, 1,650) vs 1,500 (1,350, 1,718.8) I.U., p = 0.137]. The duration of ovarian stimulation was shortened in the letrozole group compared to the control group [9 (8, 10) vs 9 (8.3, 10) days, p = 0.027]. The letrozole and control group had a similar level of GDF-9 (0.036 ± 0.003 A.U. vs. 0.028 ± 0.004 A.U., p = 0.119, letrozole and control group, respectively) and BMP-15 (0.034 ± 0.002 A.U. vs. 0.033 ± 0.004 A.U., p = 0.923, letrozole and control group respectively) in follicular fluid. Limitations, reasons for caution This study was open-label, with limited generalizability due to 91% of ovarian stimulation being strict to the research protocol (r-FSH and antagonist protocol) and no pregnancy outcome. Wider implications of the findings The study showed no benefit of letrozole co-stimulation in women with normal ovarian reserve. Trial registration number TCTR20221125002

P-449 Association of corpus luteum activity in early pregnancy and live birth after assisted reproductive technology (ART) and intrauterine insemination (IUI)

Abstract Study question What is the incidence of low corpus luteum activity in early pregnancy, and how are endogenous progesterone levels and live birth achievement associated? Summary answer Frequently occurring low corpus luteum activity (progesterone-level) in early pregnancy after ART and IUI strongly predicts pregnancy demise, though not independent of trophoblast activity (hCG-level). What is known already Ovarian stimulation and human chorion gonadotropine (hCG) administration may induce a luteal phase defect via negative feedback on the hypothalamic-pituitary-ovarian (HPO) axis. Luteal phase support (LPS) is routinely administered with bio-identical progesterone or oral dydrogesterone (DYD). DYD has high oral availability, minimal interaction with the pituitary gland, and no cross-reactivity in enzyme-linked immunosorbent assay (ELISA) with progesterone. Therefore, utilizing DYD as LPS in IVF/ICSI or ovulatory IUI cycles provides a unique perspective to assess endocrine luteal activity. While various studies explored progesterone and hCG post-IVF or IUI, none focused solely on the corpus luteum’s sole endocrine function and its outcomes. Study design, size, duration This single-center, retrospective study (with institutional review board approval) investigated hCG and progesterone serum levels after IVF/ICSI cycles or IUI cycles supported with DYD as the sole LPS. The study aims to assess their predictive value, individually and in combination, for sustaining pregnancy. Data from 189 IVF/ICSI and 198 IUI early pregnancies, respectively, with positive hCG test between January 2017 and June 2022, was extracted from the patient management system at the University Fertility Center. Participants/materials, setting, methods Included were only first IVF/ICSI and IUI treatment-cycles with serum hCG value ≥ limit of detection (0.6 IU/l) between days 9 and 16 after fresh embryo transfer or IUI, respectively. Additionally to hCG, endogenous progesterone was determined and the relationship between these and pregnancy maintenance was investigated using logistic regression analysis. Inclusion criteria encompassed hCG-triggered cycles using DYD as the sole LPS, administered at 30 and 20 mg daily for IVF/ICSI and IUI therapy, respectively. Main results and the role of chance The 10th, 25th, 50th and 75th quantiles of serum progesterone are at 0.28, 3.75, 33.0 and 98.7 µg/l in IVF/ICSI cycles and 0.48, 2.70, 18.40 and 26.6 µg/l in IUI cycles. Women in the first quartile of progesterone levels had nearly exclusively pregnancy demise: live birth rate 3/47 (7%, 95% confidence interval (CI) 1-19%) and 0/47 (0%, 95% CI 0-7.5%) in IVF/ICSI and IUI cycles, respectively. In both IVF/ICSI and IUI, progesterone and hCG were highly correlated (correlation coefficient 0.83 in both cases). Accordingly, the association of serum hCG levels with live birth achievement was similar in quartile analyses. Using receiver operating characteristic (ROC) curves and Youden’s indices, the optimal cut-off values for predicting live birth were determined as follows: 16.49 µg/l (89 % sensitivity (SN) and 59 % specificity (SP)) for IVF/ICSI and 15.89 µg/l (90 % SN and 70 % SP) for IUI therapy. Logarithmic regression analysis also revealed a significant correlation between progesterone levels and live birth in IVF/ICSI and IUI therapy, with a p-value of &amp;lt; 0.001. Limitations, reasons for caution Low progesterone in early pregnancy may be a consequence or a cause for pregnancy demise. DYD, like any other progesterone for LPS, might adversely impact corpus luteum formation and maintenance through HPO axis interaction, especially in mono-ovulatory cycles or in older women with inherently higher risk of luteal phase defect. Wider implications of the findings Ovarian stimulation and hCG-administration may induce a luteal phase defect with insufficient luteal activity in early pregnancy, even up to luteolysis, with potential consequences for pregnancy maintenance and maternal/fetal health. Future treatment protocols may require exploring an optimal luteotropic state at pregnancy’s outset, necessitating the establishment of relevant markers. Trial registration number not applicable

Genetic hypogonadal (Gnrh1hpg) mouse model uncovers influence of reproductive axis on maturation of the gut microbiome during puberty.

The gut microbiome plays a key role in human health and gut dysbiosis is linked to many sex-specific diseases including autoimmune, metabolic, and neurological disorders. Activation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty leads to sexual maturation and development of sex differences through the action of gonadal sex steroids. While the gut microbiome also undergoes sex differentiation, the mechanisms involved remain poorly understood. Using a genetic hypogonadal (hpg) mouse model, we sampled the fecal microbiome of male and female wild-type and hpg mutant mice before and after puberty to determine how microbial taxonomy and function are influenced by age, sex, and the HPG axis. We showed that HPG axis activation during puberty is required for sexual maturation of the gut microbiota composition, community structure, and metabolic functions. We also demonstrated that some sex differences in taxonomic composition and amine metabolism developed independently of the HPG axis, indicating that sex chromosomes are sufficient for certain sex differences in the gut microbiome. In addition, we showed that age, independent of HPG axis activation, led to some aspects of pubertal maturation of the gut microbiota community composition and putative functions. These results have implications for microbiome-based treatments, indicating that sex, hormonal status, and age should be considered when designing microbiome-based therapeutics.

Subacute exposure to a mixture of tributyltin plus mercury impairs reproductive axis function, exacerbating premature ovarian insufficiency features and reducing fertility in female rats

Tributyltin (TBT) and mercury (Hg) are endocrine-disrupting chemicals that individually cause reproductive complications. However, the reproductive consequences of exposure to a mixture of TBT plus Hg are not well known. We hypothesized that exposure to a mixture of TBT plus Hg would alter hypothalamic-pituitary-gonadal (HPG) axis function. Female rats were exposed to this mixture daily for 15 days, after which chemical accumulation in the tissues, morphology, hormone levels, inflammation, fibrosis, and protein expression in the reproductive organs were assessed. Increases in tin (Sn) and Hg levels were detected in the serum, HPG axis, and uterus of TBT-Hg rats. TBT-Hg rats exhibited irregular estrous cycles. TBT-Hg rats showed an increase in gonadotropin-releasing hormone (GnRH) protein expression and follicle-stimulating hormone (FSH) levels and a reduction in luteinizing hormone (LH) levels. Reduced ovarian reserve, antral follicles, corpora lutea (CL) number, and estrogen levels and increased atretic and cystic follicles were found, suggesting that TBT-Hg exposure exacerbated premature ovarian insufficiency (POI) features. Furthermore, TBT-Hg rats exhibited increased ovarian mast cell numbers, expression of the inflammatory markers IL-6 and collagen deposition. Apoptosis and reduced gland number were observed in the uteri of TBT-Hg rats. A reduction in the number of pups/litter for 90 days was found in TBT-Hg rats, suggesting impaired fertility. Strong negative correlations were found between serum and ovarian Sn levels and ovarian Hg levels and ovarian reserve and CL number. Collectively, these data suggest that TBT plus Hg exposure leads to abnormalities in the HPG axis, exacerbating POI features and reducing fertility in female rats.

Regulating effect of Gegen Decoction on hypothalamic-pituitary-ovarian axis in mice with primary dysmenorrhea

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_(2α)(PGF_(2α)), gonadotropin-releasing hormone(GnRH), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and estrogen(E_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_(2α), GnRH, FSH, LH, and E_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_(2α), GnRH, FSH, LH, and E_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_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.

Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men

Background The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic–pituitary–adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men. Methods Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males’ Symptoms (AMS) questionnaire were obtained from 225 healthy adult men. Results A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15–17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70). Conclusions The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

Body Condition in Small Ruminants—Effects of Nutrition on the Hypothalamic–Pituitary–Gonad Axis and Ovarian Activity That Controls Reproduction

Nutritional status plays a vital role in regulating ovary activity. This regulation is mediated by the hypothalamus–pituitary–gonad axis and by effects exerted directly on the ovary. Therefore, to achieve the best reproductive performance, it is essential to know how the nutritional status affects the secretion of GnRH, gonadotrophins, and sex steroid hormones. Adequate body reserves and energy balance are critical for optimal reproductive performance in sheep and goats. However, over- or under-conditioned animals experience issues like extended anestrus, irregular ovarian cycles, and reduced conception. Body condition scoring allows for the evaluation of the relationships between adiposity, nutritional status, and fertility. Acute feed deficits briefly stimulate processes, but chronic restrictions suppress pulsatile LH release, disrupting ovarian function. The process of follicle development is a very complex one which involves intricate interactions between the pituitary gonadotrophins and metabolic hormones as well as between the locally produced factors by the ovarian somatic and germ cells including the IGF system and the TGF-β superfamily members. Genotype and nutrition are factors that have an impact on follicular development, and seasonal factors are also involved. This review will give a brief overview on how the body condition can be evaluated and the effects of nutrition on the hypothalamus–pituitary–gonad axis and ovarian activity, which are responsible for reproductive regulation. This paper presents a clear and reasonable summary of the pathway that runs from the nutritional status of small ruminants to ovarian activity through the hypothalamic–pituitary–gonadal axis. This review summarizes methods for body condition evaluation in small ruminants and evidence regarding acute versus prolonged nutritional impacts on the hypothalamic–pituitary–gonadal axis and ovarian activity controlling reproduction.

Intracerebroventricular PROK2 infusion could increase the secretion of male reproductive hormones by stimulating the HPG axis.

Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated. Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5nmol and 4.5nmol PROK2 intracerebroventricularly for 7days via an osmotic mini pump (1µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups. The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.

Expression of genes related to gonadal development and construction of gonadal DNA methylation maps of Trachinotus blochii under hypoxia

Chronic hypoxia can affect the growth and metabolism of fish and potentially impact gonadal development through epigenetic regulation. Trachinotus blochii (Golden pompano) is widely cultured near the coast and is sensitive to low oxygen conditions. We found that hypoxia and reoxygenation processes acted on multiple targets on the HPG axis, leading to endocrine disorders. Changes in the expression of key genes in the brain (gnrh), pituitary (fsh and lh), ovaries (cyp19a1a, foxl2, and er), and testes (dmrt1, ar, sox9, and gsdf) were associated with significant decreases in estrogen and testosterone levels. Hypoxia and reoxygenation lead to changes in DNA methylation levels in the gonads. Hypoxia upregulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in females and dnmt3a and dnmt3b in males, while reoxygenation down-regulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in males. Whole genome methylation sequencing showed that the number of differentially methylated regions was highest on chromosome 10 (5192) and lowest on chromosome 24 (275). Differentially methylated genes in females and males, as well as between males and females, were enriched in the oxytocin signaling pathway, fatty acid metabolism pathway, and HIF-1a pathway. In summary, hypoxia and reoxygenation can induce endocrine disorders, affect the expression of HPG axis genes, change the methylation pattern and modification pattern of gonad DNA, and then have potential effects on gonad development.

Chronic Lead Exposure Impairment of Hypothalamic-Pituitary-Gonadal Axis in Adult Male Wistar Rats: Biochemical and Histomorphological Evidence

Introduction: The upsurge in male infertility has been associated with impaired hypothalamic-pituitary-gonadal (HPG) axis. There is a dearth of conclusive empirical data as to the deleterious impacts of heavy metal intoxication on male reproductive functioning through the HPG axis. Objective: This study seeks to elucidate the possible effects of chronic lead exposure on HPG signalling activities via biochemical and histopathological assessment. Experimental Section/Material and Methods: Forty adult male Wistar rats were randomised into four experimental groups (n=10). Group A, the control group received standard feed and water ad libitume. In Groups B, C and D, animals were orally administered lead acetate at concentrations of 2.5% 3.0% and 3.5%, respectively, using a stock solution of 150mg/kg once daily for 35 days. After the treatment period, all animals were fasted overnight and euthanized by cervical dislocation. Blood levels of anterior pituitary hormones (FSH and LH) were analysed using standard methods. Statistical analyses was done on graph pad prism. Testicular tissue was processed routinely for histopathological analyses using different stains. Results: Hormonal assays showed no significant changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (p&gt;0.05) levels across groups. However, histological examination revealed alterations in testicular architecture, including disrupted spermatogonia cell arrangement and reduced Sertoli cell numbers, indicative of adverse effects on spermatogenesis. Conclusion: Chronic lead exposure adversely affects testicular histomorphology in adult male Wistar rats, potentially impacting reproductive function. While hormonal levels remain relatively unaffected, alterations in testicular structure suggest a direct impact on gonadal functions at a cellular level.

Hypogonadotropic hypogonadism in male tilapia lacking a functional rln3b gene

Relaxin 3 is a neuropeptide that plays a crucial role in reproductive functions of mammals. Previous studies have confirmed that rln3a plays an important role in the male reproduction of tilapia. To further understand the significance of its paralogous gene rln3b in male fertility, we generated a homozygous mutant line of rln3b in Nile tilapia. Our findings indicated that rln3b mutation delayed spermatogenesis and led to abnormal testes structure. Knocking out rln3b gene resulted in a decrease in sperm count, sperm motility and male fish fertility. TUNEL detection revealed a small amount of apoptosis in the testes of rln3b−/− male fish at 390 days after hatching (dah). RT-qPCR analysis demonstrated that mutation of rln3b gene caused a significant downregulation of steroid synthesis-related genes such as cyp17a1, cyp11b2, germ cell marker gene, Vasa, and gonadal somatic cell marker genes of amh and amhr2. Furthermore, we found a significant down-regulation of hypothalamic-pituitary-gonadal (HPG) axis-related genes, while a significantly up-regulation of the dopamine synthetase gene in the rln3b−/− male fish. Taken together, our data strongly suggested that Rln3b played a crucial role in the fertility of XY tilapia by regulating HPG axis genes.

Dampened HPG axis activity and improved reproductive lifespan in dummerstorf superfertile mouse lines

Dampened HPG axis activity and improved reproductive lifespan in dummerstorf superfertile mouse lines

Effects of social environments on male primate HPG and HPA axis developmental programming.

Developmental plasticity is particularly important for humans and other primates because of our extended period of growth and maturation, during which our phenotypes adaptively respond to environmental cues. The hypothalamus-pituitary-gonadal (HPG) and hypothalamus-pituitary-adrenal (HPA) axes are likely to be principal targets of developmental "programming" given their roles in coordinating fitness-relevant aspects of the phenotype, including sexual development, adult reproductive and social strategies, and internal responses to the external environment. In social animals, including humans, the social environment is believed to be an important source of cues to which these axes may adaptively respond. The effects of early social environments on the HPA axis have been widely studied in humans, and to some extent, in other primates, but there are still major gaps in knowledge specifically relating to males. There has also been relatively little research examining the role that social environments play in developmental programming of the HPG axis or the HPA/HPG interface, and what does exist disproportionately focuses on females. These topics are likely understudied in males in part due to the difficulty of identifying developmental milestones in males relative to females and the general quiescence of the HPG axis prior to maturation. However, there are clear indicators that early life social environments matter for both sexes. In this review, we examine what is known about the impact of social environments on HPG and HPA axis programming during male development in humans and nonhuman primates, including the role that epigenetic mechanisms may play in this programming. We conclude by highlighting important next steps in this research area.

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

IntroductionLong-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men. MethodsIn this proof-of-concept, single-site, open longitudinal pilot study, AAS dependent men with continuous AAS use and a desire to permanently discontinue use, were given endocrine therapy. The treatment included 25 mg clomiphene citrate (CC) every second day for 16 weeks, transdermal testosterone daily during the first four weeks, and if indicated, human chorionic gonadotropin (hCG) injections for a maximum of eight weeks. Physical exams including blood collection and online questionnaires were completed every four and two weeks, respectively. ResultsTen participants, with median age 32 years (interquartile range 30–45), with mean ± standard deviation AAS use of 11 ± 4 years, completed the CC intervention. Seven participants received hCG as part of their treatment protocol. Mild adverse events included headaches, dizziness, and mood swings, and no serious adverse events occurred. During the intervention, there was a decrease in levels of hematocrit, hemoglobin and ALT (alanine aminotransferase), as well as an increase in serum FSH (follicle stimulating hormone), LH (luteinizing hormone) and SHBG (sex hormone binding globulin). Five of ten participants reached a total testosterone level within normal range (9–30 nmol/l). The HPG axis response varied greatly among participants, and was not aligned with the severity of ASIH related withdrawal symptoms. ConclusionsThe findings from this proof-of-concept study may guide future randomized controlled trials aiming to investigate potential endocrine therapeutic approaches to ASIH.

The role of kisspeptin in female and male reproduction

Kisspeptin is a neuropeptide responsible for controlling the synthesis of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The G-protein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R) is involved in its action. The comprehension of kisspeptin and its actions represents a significant breakthrough in the field of reproductive biology. Kisspeptins play a crucial role in the development and optimal functioning of the reproductive system in both female and male. Additionally, it contributes to the onset of puberty, regulating feedback processes, and influencing sexual desire and arousal. It regulates a number of reproductive functions in women, including ovulation, lactation, ovarian development, follicle development, oocyte maturation, and pregnancy via the hypothalamic-pituitary-gonadal (HPG) axis. Spermatogenesis, sperm function, Leydig cells, and reproductive behaviour are all impacted by it in men. Infertility and polycystic ovarian syndrome (PCOS) are among the diseases linked to kisspeptin dysregulation, according to the research. For potential future use in diagnosing and treating problems, it may be helpful to understand the mechanisms behind kisspeptin's effects on the reproductive system. This review focuses on the regulatory function of kisspeptin on the HPG axis and the impact of kisspeptin on reproductive processes in both female and male.