Hypothalamic-pituitary-gonadal Axis Research Articles

Restorative effects of melatonin on bisphenol a-induced interference of gene expression in hypothalamic pituitary axis following early exposure

Bisphenol-A is a standard monomer used in manufacturing plastics and epoxy resins, and it is widely used in food preservation and packaging. It is an endocrine-disrupting chemical miming the endogenous estradiol hormone. Melatonin regulates sleep-wake cycles and plays essential physiological roles in the body through its antioxidative properties. This research aims to ascertain the impact of Bisphenol A on the hypothalamic-pituitary-ovarian axis and determine melatonin's function on possible BPA-induced effects. Six adult male Wistar rats and 12 adult female Wistar rats of proven fertility were bred and organized into groups. These animals were subjected to subcutaneous injections of high and low doses of bisphenol A from postnatal days 0-3, then oral melatonin. The rats were allowed to mature into full-grown adults and euthanized at 120 ±4 days. The serum and hypothalamic-pituitary-ovarian tissues were collected for various assays. Compared to the control groups, groups administered varying doses of bisphenol A showed significant overexpression of estrogen and androgen receptors. Administration of Melatonin showed some reversal and reparative effects on damage of the hypothalamic pituitary ovarian axis. Elevated estrogen receptor levels induced by Bisphenol A altered receptor function. Melatonin showed some promising reparative effects.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic–pituitary–gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand–receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

The curious case of the hypothalamic-pituitary-gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids.

The naked mole-rat (Heterocephalus glaber) is a unique model mammal in which to study socially induced inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.

Bone marrow mesenchymal stem cells expressing Neat-1, Hotair-1, miR-21, miR-644, and miR-144 subsided cyclophosphamide-induced ovarian insufficiency by remodeling the IGF-1–kisspeptin system, ovarian apoptosis, and angiogenesis

Ovarian insufficiency is one of the common reproductive disorders affecting women with limited therapeutic aids. Mesenchymal stem cells have been investigated in such disorders before yet, the exact mechanism of MSCs in ovarian regeneration regarding their epigenetic regulation remains elusive. The current study is to investigate the role of the bone marrow-derived mesenchymal stem cells (BM-MSCs) lncRNA (Neat-1 and Hotair1) and miRNA (mir-21-5p, mir-144-5p, and mir-664-5p) in mitigating ovarian granulosa cell apoptosis as well as searching BM-MSCs in altering the expression of ovarian and hypothalamic IGF-1 – kisspeptin system in connection to HPG axis in a cyclophosphamide-induced ovarian failure rat model. Sixty mature female Sprague Dawley rats were divided into 3 equal groups; control group, premature ovarian insufficiency (POI) group, and POI + BM-MSCs. POI female rat model was established with cyclophosphamide. The result revealed that BM-MSCs and their conditioned media displayed a significant expression level of Neat-1, Hotair-1, mir-21-5p, mir-144-5p, and mir-664-5p. Moreover, BM-MSCs transplantation in POI rats improves; the ovarian and hypothalamic IGF-1 – kisspeptin, HPG axis, ovarian granulosa cell apoptosis, steroidogenesis, angiogenesis, energy balance, and oxidative stress. BM-MSCs expressed higher levels of antiapoptotic lncRNAs and microRNAs that mitigate ovarian insufficiency.

Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

The function of juvenile-adult transition axis in female sexual receptivity of Drosophila melanogaster.

Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.

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...

P10-18 Bayesian benchmark dose modelling of hypothalamic–pituitary–ovarian axis endpoints to assess DEHP exposure effects in female mice

P10-18 Bayesian benchmark dose modelling of hypothalamic–pituitary–ovarian axis endpoints to assess DEHP exposure effects in female mice

Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice

BackgroundThe hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice. Method and resultImmunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice. ConclusionThis study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.

Diagnostic utility of the average peak LH levels measured during GnRH stimulation test.

Gonadotropin-releasing hormone (GnRH) test is the gold standard test to evaluate the hypothalamus-pituitary-gonadal (HPG) axis for the diagnosis of central precocious puberty (CPP). However, the diagnosis of cases with clinical features of CPP whilst have borderline peak luteinizing hormone (LH) remain challenges. We aimed to evaluate diagnostic performance of the average of LH levels measured during GnRH stimulation test. Cases with diagnosis of CPP and premature thelarche (PT) who had a GnRH stimulation test results were retrospectively reviewed. Anthropometric measurements (weight, height, and body mass index), age and sex-specific standard deviation scores, growth velocity, puberty stages, bone ages, serum FSH, LH, and estradiol levels were measured by electrochemiluminescence immunological method (ECLIA), and the GnRH stimulation test results, which performed by obtaining venous blood samples at basal, 20th, and 40th minutes for FSH and LH measurement, were recorded. A total of 76 girls (38 CPP, 38 PT) were included. We detected an average peak LH cut-off value of 4.25 IU/L with 94.7 % sensitivity and 97.4 % specificity, a 97.3 % positive predictive value, and a 94.9 % negative predictive value in GnRH test to differentiate cases with CPP from PT. This is the first study evaluating the diagnostic utility of the average of LH levels measured during GnRH stimulation test. We showed that the average of two LH measurements has a high diagnostic performance. Therefore, it can be used as a valid and reliable diagnostic tool for assessment of HPG axis activation, particularly for cases with a borderline peak LH level.

Pathological characteristics of SRY-negative 38,XX-DSD pigs: A family case report

Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomes, gonads, or anatomical sex. XX-DSD pigs disrupt the production of high-quality breeding pigs and impede the advancement of the pig industry. However, the etiology of XX-DSD pigs remains unclear. Systematic reports on the genetic and pathological characteristics of prepubescent XX-DSD pigs in familial contexts are sparse. This study aimed to investigate the genetic and pathological features of one-month-old XX-DSD pigs within a familial context and to provide phenotypic information to elucidate the pathogenic mechanisms of XX-DSD pigs. The findings revealed that inbreeding within the XX-DSD family may contribute to the pathogenesis of XX-DSD pigs. All XX-DSD pigs in the family had a chromosomal sex of female and were male pseudohermaphrodites. The degree of masculinization of the reproductive organs varied among XX-DSD pigs, demonstrating phenotypic heterogeneity. HE staining showed that the testes of prepubescent XX-DSD pigs contained vesicles in the seminiferous tubules, with or without vestigial germ cells. Ultrastructural analyses indicated that sertoli cells, leydig cells and germ cells in the testes of XX-DSD pigs exhibited pathological damage, confirming impaired testicular function. Immunofluorescence staining revealed high expression of SRY-box transcription factor 9 (SOX9) in XX-DSD pig testicular tissues, while forkhead box L2 (FOXL2) was minimally expressed. Disordered secretion of reproductive hormones in prepubescent XX-DSD pigs indicated abnormal hypothalamic-pituitary-gonadal axis (HPGA) function. This study elucidates the genetic and pathological characteristics of prepubescent XX-DSD pigs in familial case, providing valuable insights for further exploration of the pathogenic mechanisms underlying XX-DSD.

Transcriptome Analysis of Hypothalamic-Pituitary-Ovarian Axis Reveals circRNAs Related to Egg Production of Bian Chicken.

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.

Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression.

This comprehensive review explores the intricate relationship between the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and aggression. It provides a detailed overview of the physiology and functioning of these axes, as well as the implications for aggressive behavior. The HPA axis, responsible for the stress response, is activated in response to various stressors and can influence aggressive behavior. Glucocorticoids, such as cortisol, play a crucial role in stress-induced activation of the HPA axis and have been implicated in aggressive tendencies. Chronic stress can dysregulate the HPA axis, leading to alterations in cortisol levels and potentially contributing to aggressive behavior. The HPG axis, particularly the androgen hormone testosterone, is also closely linked to aggression. Animal and human studies have consistently shown a positive association between testosterone levels and aggression. The androgen receptors in the brain's neural circuitry play a critical role in modulating aggressive behavior. Interactions between the HPA and HPG axes further contribute to the regulation of aggression. Feedback mechanisms and crosstalk between these axes provide a complex system for the modulation of both stress and reproductive functions, which can impact aggressive behavior. Additionally,the influence of stress on reproductive functions, particularly the role of androgens in stress-induced aggression, adds further complexity to this relationship. The review also discusses the future directions and implications for clinical interventions. Understanding the neurobiological mechanisms underlying aggression requires integrating molecular, cellular, and circuit-level approaches. Translational perspectives, including animal models and human studies, can bridge the gap between basic research and clinical applications. Finally, therapeutic strategies for aggression-related disorders are explored, highlighting the importance of targeted interventions based on a comprehensive understanding of the interactions between the HPA and HPG axes. In conclusion, this review provides a comprehensive overview of the physiological and neurobiological mechanisms underlying aggression, with a specific focus on the interplay between the HPA and HPG axes. By elucidating the complex interactions between stress, hormones, and aggressive behavior, this research paves the way for future investigations and potential therapeutic interventions for aggression-related disorders.

Luteal phase sertraline treatment of premenstrual dysphoric disorder (PMDD): Effects on markers of hypothalamic pituitary adrenal (HPA) axis activation and inflammation

RationalePremenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD. AimsThe goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers. MethodsParticipants were females age 18–50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1β were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity. ResultsThe sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1β, nor TNF-α (p’s>0.05). ConclusionSerum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.

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.

Integration analysis of pituitary proteome and transcriptome reveals fertility-related biomarkers in FecB mutant Small Tail Han sheep.

The Booroola fecundity mutation (FecB) in Small Tail Han sheep has been shown to enhance ovulation rates and litter sizes by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Despite the pituitary's role in reproductive regulation, its involvement in FecB-induced ovulation remains understudied. Our study aimed to fill this gap by analyzing pituitary tissues from FecB homozygous (BB) and wild-type (WW) ewes during luteal and follicular phases using tandem mass tag-based protein quantification and the DIABLO framework for proteomic and transcriptomic data integration. Significant differences in 277 proteins were observed across estrus periods, with network analysis highlighting the voltage-dependent calcium channel L-type alpha-1C as a key convergence point in oxytocin signaling and GnRH secretion pathways. The DIABLO method revealed a strong correlation (0.98) between proteomic and transcriptomic datasets, indicating a coordinated response in FecB ewes. Notably, higher expression levels of Follicle Stimulating Hormone Subunit Beta (FSHB) and Luteinizing Hormone Subunit Beta (LHB) were found in BB ewes during the follicular phase, potentially due to elevated E2 concentrations. Furthermore, our analysis identified genes related to the Gamma-aminobutyric acid type A receptor family (GABRA2, GABRG1, GABRB1) in the pituitary, with GABRB1 showing higher expression in BB ewes. This suggests a role for GABA in modulating GnRH and gonadotropin feedback loops, potentially contributing to the FecB mutation's effect on ovulation. This study provides novel insights into the pituitary's role in fertility among FecB sheep, identifying GABA as a potential regulatory factor within the HPG axis. The findings also open avenues for discovering new biomarkers in pituitary endocrinology for sheep breeding purposes.

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.

Menstrual Irregularity: A Physiological Adaptation to Cope Perceived Stress.

Menstrual cycle characteristics are regulated hormonally and are integrated at the level of the hypothalamus. Stress can affect the hypothalamic-pituitary gonadal axis. The objective of the study was to analyse the stress levels of women and compare their autonomic tone and menstrual characteristics. A group of 100 apparently healthy, young, female volunteers were included in this pilot cohort study. Subjects were assessed for perceived stress using the Perceived Stress Scale 14 Item (PSS-14) questionnaire, underwent a heart rate variability (HRV) test on the second, 10th, and 21st days of their menstrual cycle, and their menstrual history was recorded.The statistical analysis was done using Statistical Product and Service Solutions (SPSS, version 21.0; IBM SPSS Statistics for Windows, Armonk, NY) software. Metric data were expressed in terms of numerical value and analysed as mean ± SD. Paired Student's T-test was used to compare the HRV data of all three days of the menstrual cycle separately, and p value<0.05 was considered significant. Menstrual irregularity was complained of by 13 subjects (Group A), and the rest (87 subjects) reported regular menses (Group B). The perceived stress scores of Group A were significantly higher than Group B (32.53±5.062 vs 28.057±7.618; p=0.044). On second day, Group A had higher median R-R interval (714.38±106 vs 656.84±73.50 ms; p=0.015) and lower average heart rate (85.85±12.07 vs 92.39±9.98 bpm; p=0.034) than Group B, suggesting parasympathetic dominance. On the 10th day, Group A had a higher standard deviation of heart rate (7.09±1.88 vs 5.97±1.71 bpm; p=0.032) and a very low-frequency band (1105.94±984.12 vs 730.49±557.41 μs2; p=0.046) than Group B, indicating parasympathetic dominance in Group A. On the 21st day, Group A had a higher standard deviation of R-R interval (58.19±20.46 vs 44.85±14.55 ms; p=0.004), root mean square standard deviation (55.71±29.84 vs 31.89±15.99 ms; p<0.001), percentage of R-R differing by 50 ms (19.20±19.58 vs 10.87±10.31%; p=0.020), total power (3,440.23±2722.29 vs 2,068.28±1,322.49 μs2; p=0.004), high-frequency band (1,247.57±1173.54 vs 539.06±HPO438.92 μs2; p<0.001), standard deviation ratio of the Poincaré plot (0.53±0.19 vs 0.39±0.16; p=0.003), normalised HF (44.0±12.9 vs 35.4±10.6; p=0.009), and a lower LF/HF ratio (1.43±0.80 vs 2.11±1.16; p=0.043) and normalised LF (53.9±14.4 vs 64.1±11.9; p=0.006) than Group B, suggesting higher parasympathetic tone of Group A than Group B. Analysing these results, it can be concluded that, in apparently healthy young women, menstrual irregularity is a physiological adaptation to combat perceived stress and maintain parasympathetic dominance.

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.