Hypothalamic-pituitary-gonadal Axis Research Articles

Effects of Recombinant Leptin Proteins on the Expression of Key Genes in the HPG Axis and Liver of Tongue Sole In Vitro

Leptin (Lep) plays a crucial role in controlling food intake and maintaining energy balance in mammals. While several studies have shown the presence of multiple leptin genes in teleosts, limited information is currently available on how sex steroid hormones regulate the expression of these genes in fish. In this study, we used two previously expressed and purified leptin proteins to incubate four tissues in vitro (hypothalamic-pituitary-gonadal axis and liver) and used the RT-qPCR method to detect the expression of genes related to growth and reproduction in tongue sole (Cynoglossus semilaevis). The results showed that both recombinant LepA and LepB proteins of tongue sole almost entirely suppressed the expression of genes related to growth and reproduction in the hypothalamic-pituitary-gonadal axis and liver, while LepB may have had a positive role on steroid synthesis in gonads. Further, a high concentration of LepA facilitated the expression of IGF-Ι in liver. At the same time, we utilized human leptin to incubate four tissues in vitro; although most of them had trends similar to those stimulated with tongue sole leptins, there were still some differences, indicating differences among leptin homologs between humans and fishes. To our knowledge, this is the first study to explore the function of tongue sole LepA and LepB within the hypothalamic-pituitary-gonadal axis and liver in vitro. Our results provide a valuable resource and foundation for future studies.

Effects of the COVID-19 pandemic on the incidence of central precocious puberty; a narrative review.

Central precocious puberty (CPP) is the premature activation of the hypothalamus-pituitary-gonadal axis, resulting in the early development of secondary sexual characteristics. CPP classically occurs before the age of 8 years in girls and 9 years in boys. The aetiology of thisprecocious onset of puberty is governed by complex mechanistic interactions between genetic and environmental factors. The rates of CPP have been documented to have been rising before the COVID-19 pandemic; despite this, the incidence of CPP has increased exponentially since the start of the pandemic. There are multiple theories potentially explaining this change in incidence of CPP over COVID-19. These include the direct effect of SARS-coV-2 infection, increasing body mass index of adolescents oversequential lockdowns, changes in sleep patterns, increased use of electronic devices and levels of stress, andadditionally potential earlier detection of signs of CPP by parents and carers. Whilst there is evidence from observational cohorts, case studies and animal models for each of these factors, it is difficult to definitively prove which has had the greatest impact due to the mainly retrospective nature of the human research that has been conducted. Moreover, studies set in diverse settings with varying population make comparison complex. Additionally, each country responded differently to the COVID-19 pandemic and the lockdowns varied between locations, hence the effect of lockdown was not equal or universal. Despite this, similar trends have been identified, with various lifestyle changes that occurred over the pandemic being potentially influential factors on the development ofCPP.

Central regulation of reproduction in amphibians.

This review article includes a literature review of synteny analysis of the amphibian gonadotropin-releasing hormone (GnRH) genes, the distribution of GnRH 1 and GnRH2 neurons in the central nervous system of amphibians, the function and regulation of hypophysiotropic GnRH1, and the function of GnRH1 in amphibian reproductive behaviors. It is generally accepted that GnRH is the key regulator of the hypothalamic-pituitary-gonadal axis. Three independent GnRH genes, GnRH1, GnRH2, and GnRH3, have been identified in vertebrates. Previous genome synteny analyses suggest that there are likely just two genes, gnrh1 and gnrh2, in amphibians. In three groups of amphibians: Anura, Urodela, and Gymnophiona, the distributions of GnRH1 and GnRH2 neurons in the central nervous system have also been previously reported. Moreover, these neuronal networks were determined to be structurally independent in all species examined. The somata of GnRH1 neurons are located in the terminal nerve, medial septum (MS), and preoptic area (POA), and some GnRH1 neurons in the MS and POA project into the median eminence. In contrast, the somata of GnRH2 neurons are located in the midbrain tegmentum. In amphibians, GnRH1 neurons originate from the embryonic olfactory placode, while GnRH2 neurons originate from the midbrain. The characterization and feedback regulation mechanisms of hypophysiotropic GnRH1 neurons in amphibians, the involvement of GnRH1 in amphibian reproductive behavior, and its possible mechanism of action should be elucidated in future.

Long-term tralopyril exposure results in endocrinological and transgenerational toxicity: A two-generation study of marine medaka (Oryzias melastigma)

This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 μg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.

Diagnostic value of adenohypophyseal MRI features in female children with precocious puberty

To evaluate the diagnostic value of adenohypophyseal magnetic resonance imaging (MRI) features for precocious puberty (PP) in female children and also to establish a non-invasive diagnostic approach in clinics. A total of 126 female children (37, 57, and 32 female children clinically diagnosed with central PP [CPP], incomplete PP [IPP], and controls, respectively) were enrolled in this study. Data were collected and analysed using analysis of variance. Pearson correlation and stepwise multivariate linear regression analysis were used to examine the association and build prediction models. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy. The values of adenohypophysis volume (aPV), adenohypophysis height (aPH), and signal-intensity ratio (SIR), height, weight, and seven laboratory testing characteristics were correlated closely with the activation status of the hypothalamic-pituitary-gonad axis in the different groups (all p<0.05). Model 1 including aPV, weight, and aPH and Model 2 including SIR, aPV, and height were built to obtain predicted luteinising hormone (LH; R2=0.271) and LH/follicle stimulating hormone (FSH; R2=0.311). ROC analysis showed the predicted LH, predicted LH/FSH, and aPV were the top 3 best predictors in distinguishing CPP from controls (AUC=0.969, 0.949, and 0.938) while predicted LH/FSH was the best predictor in distinguishing CPP from IPP and controls (AUC=0.829 and 0.828). The adenohypophysis volume itself and the prediction models including main adenohypophyseal MRI features increased diagnostic efficiency for PP and offered a non-invasive and credible diagnostic method.

An Ayurvedic Management of Bandhyatva due to Dhatukshya

Women health is the prime concern in Ayurveda classics, all gynecological problems are described under Yonivyapada and Aartav Vikara. Due to stressful lifestyle of today’s women, many physiological changes occur that ends with the disruption of HPO axis leading to various gynecological disorders. Eventually all these factors lead to infertility. A female patient aged 21 years having BMI 18 came to OPD of Rajiv Gandhi Govt. PG Ayurvedic Hospital, Paprola, with complaint of inability to conceive since last 3 years. She was taking treatment for the same from last one year by consulting some private practitioner All the routine investigations of both partners were within normal range. Semen analysis of her husband was normal. The causative factor behind unexplained infertility was elicited as Dhatukshya Janya Bandhyatva. Aim and Objectives: To study the efficacy of Balya and Brihmana Chikitsa in case of Dhatukshya Janya Bandhyatva. Methodology: Mustadi Yapna Basti and Shatavariyadi Ghrit Anuvasan Basti given in Kala Krama followed by Phalaghrita Uttar Basti in three consecutive cycles for Kshetra preparation along with oral medication. Discussion: Vata and Dhatu Kshaya are considered as main factors of Bandhyatva in this case. Thus, the treatment is directed towards pacifying the vitiated Vata Dosha. Here Yapna, Anuvasan and Uttar Basti lead to Dhatupushti by correcting the Jatharagni and Dhatvagni. Results: After this treatment patient conceived spontaneously. Conclusion: Dhatukshya a major factor which is often ignored while treating infertility patients should be paid prime concern when no other considerable etiological factor found during investigations.

Beyond the Metabolic Syndrome: Non-Obvious Complications of Obesity in Children.

Obesity is currently one of the most significant public health challenges worldwide due to the continuous increase in obesity rates among children, especially younger children. Complications related to obesity, including serious ones, are increasingly being diagnosed in younger children. A search was performed from January 2023 to September 2023 using the PubMed, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases. The focus was on English-language meta-analyses, systematic reviews, randomized clinical trials, and observational studies worldwide. Four main topics were defined as follows: disorders of glucose metabolism; liver disease associated with childhood obesity; the relationship between respiratory disorders and obesity in children; and the effects of obesity on the hypothalamic-pituitary-gonadal axis and puberty. Understanding potential complications and their underlying mechanisms can expedite the diagnostic process and enhance the effectiveness of treatment. We aspire that this study will bring insight into the often-overlooked complications associated with obesity.

English

Introduction: The menstrual cycle (MC) is the second most important biological rhythm, regulated by the hypothalamicpituitary-ovarian axis and all the hormones involved in it. In addition to reproductive functions, it is speculated that changes in hormone production during different phases of the menstrual cycle may influence other physiological systems, which may have an impact on women’s physical performance. In this way, studying the influences of the menstrual cycle on physical exercises gains importance, since little is said about the organization of strategies and intervention for the performance of physical exercises that take into account the possible impacts and changes caused by the MC. Objective: To review the influence of MC in the practice of aerobic and resistance exercises. Material and method: The search for articles was carried out in the databases: PubMed and Google Scholar, from August to September 2021, without restriction on date and type of publication, and all articles in English and Portuguese were considered. The research was based on the phases of the menstrual cycle in eumenorrheic young women, who may or may not be athletes, but without known dysfunctions of the menstrual cycle. Conclusions: Hormonal fluctuations during MC may not significantly and directly affect the cardiorespiratory or musculoskeletal system during physical exercise, as there is the question of the biological individuality of each woman, as well as the relationship with the self-reported symptoms.

Global cerebral ischemia in adult female rats interrupts estrous cyclicity and induces lasting changes in hypothalamic-pituitary-gonadal axis signaling peptides

Persistent post-ischemic alterations to the hypothalamic–pituitary–adrenal (HPA) axis occur following global cerebral ischemia (GCI) in rodents. However, similar effects on hypothalamic-pituitary–gonadal (HPG) axis activation remain to be determined. Therefore, this study evaluated the effects of GCI in adult female rats (via four-vessel occlusion) on the regularity of the estrous cycle for 24-days post ischemia. A second objective aimed to assess persistent alterations of HPG axis activation through determination of the expression of estrogen receptor alpha (ERα), kisspeptin (Kiss1), and gonadotropin-inhibitory hormone (GnIH/RFamide-related peptide; RFRP3) in the medial preoptic area (POA), arcuate nucleus (ARC), dorsomedial nucleus (DMH) of the hypothalamus, and CA1 of the hippocampus 25 days post ischemia. Expression of glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN) and CA1 served as a proxy of altered HPA axis activation. Our findings demonstrated interruption of the estrous cycle in 87.5 % of ischemic rats, marked by persistent diestrus, lasting on average 11.86 days. Moreover, compared to sham-operated controls, ischemic female rats showed reduced Kiss1 expression in the hypothalamic ARC and POA, concomitant with elevated ERα in the ARC and increased GnIH in the DMH and CA1. Reduced GR expression in the CA1 was associated with increased GR-immunoreactivity in the PVN, indicative of lasting dysregulation of HPA axis activation. Together, these findings demonstrate GCI disruption of female rats’ estrous cycle over multiple days, with a lasting impact on HPG axis regulators within the reproductive axis.

Cadmium as an Endocrine Disruptor That Hinders the Reproductive and Developmental Pathways in Freshwater Fish: A Review

Cadmium (Cd) is a non-essential element with sub-lethal effects even at low concentrations. The persistent nature of Cd and its tendency to bioaccumulate eventually create harmful effects on water biota, including fish. Cd affects various aspects of hormonal action in fish since it bioaccumulates in the endocrine system and hinders the synthesis, secretion, and metabolic activity of hormones, causing severe damage along the hypothalamus–pituitary–gonadal axis. Linking reproductive and developmental impairments in fish with ecologically relevant concentrations of individual metals can be challenging due to the complexity of aquatic ecosystems. This review deliberated the significant and novel trends of toxicological difficulties and approaches, including elucidating environmental sources’ bioavailability and Cd-induced toxic effects in freshwater fish. Both acute and chronic exposure to Cd can cause a range of adverse effects, such as growth inhibition, impaired reproductive capacity, endocrine disruption, and developmental abnormalities in freshwater fish, as evidenced by the present review. These investigations support the concept of Cd as a naturally available pollutant that causes irreversible damage in fish. These findings will help to understand the etiology of environmental circumstances that pose substantial dangers to fish health and are also crucial for preventing and treating exposure-related reproductive disturbances in freshwater fish due to environmental pollution.

Combined exposure of beta-cypermethrin and emamectin benzoate interferes with the HPO axis through oxidative stress, causing an imbalance of hormone homeostasis in female rats

The impact of pesticides on reproductive health has been increasingly recognized. β-cypermethrin (β-CYP) and emamectin benzoate (EMB) are commonly used with agricultural workers. There are few published studies on the effects of combined poisoning of these two pesticides on the reproductive system. This study investigated the toxic effects and mechanism of β-CYP and EMB on the reproductive system of female rats based on the hypothalamic-pituitary-ovarian (HPO) axis. The hypothalamic GnRH content tended to decrease, and Kiss-1 and GPR-54 mRNA and protein expression tended to increase in exposed rats. FSH content was elevated for the pituitary gland, and Kiss-1 and GPR-54 mRNA and protein expression were enhanced in all experimental groups compared with the control group. E2 content in rat ovaries and ERα mRNA and protein expression were reduced by β-CYP and EMB. Furthermore, there were interactive effects of β-CYP and EMB on FSH and E2 release, pituitary GPR-54 mRNA and protein, and ovarian ERα mRNA expression. To investigate causes of damage, oxidative damage indicators were tested and showed that exposure to β-CYP and EMB decreased GSH-Px and SOD activities in the HPO axis, increased MDA levels in the hypothalamus and ovary together with LDH activities in the HPO axis, with an interaction effect on GSH-Px and SOD activities in the hypothalamus and pituitary gland as well as on MDA in the ovary. The above results support the screening of sensitive molecular biomarkers and evaluation of the adverse effects of pesticide exposure in greenhouse operations on reproductive health.

Alterations in Gene Expression and the Fatty Acid Profile Impact but Do Not Compromise the In Vitro Maturation of Zebrafish (Danio rerio) Stage III Ovarian Follicles after Cryopreservation.

The vitrification of ovarian follicles is a strategic tool that may contribute to advances in aquaculture and the conservation of many important species. Despite the difficulties inherent to the cryopreservation of oocytes, some successful protocols have been developed for different species, but little is known about the capacity of oocytes to develop after thawing. Therefore, the profiles of the reproductive pathway genes and fatty acid membrane composition during the initial stages of development were analyzed in fresh ovarian follicles and follicles after the vitrification process. There were differences in the expression of the hypothalamic-pituitary-gonad axis genes during the follicular development in the control group as well as in the vitrified group. Similarly, alterations in the composition of fatty acids were observed after vitrification. Despite this, many alterations were observed in the vitrified group; more than half of the stage III ovarian follicles were able to grow and mature in vitro. Therefore, the vitrification of ovarian follicles may impact them at molecular and membrane levels, but it does not compromise their capability for in vitro maturation, which indicates that the technique can be a strategic tool for aquaculture.

Photoperiod Induces the Epigenetic Change of the GNAQ Gene in OVX+E2 Ewes.

GNAQ, a member of the alpha subunit encoding the q-like G protein, is a critical gene in cell signaling, and multiple studies have shown that upregulation of GNAQ gene expression ultimately inhibits the proliferation of gonadotropin-releasing hormone (GnRH) neurons and GnRH secretion, and ultimately affects mammalian reproduction. Photoperiod is a key inducer which plays an important role in gene expression regulation by affecting epigenetic modification. However, fewer studies have confirmed how photoperiod induces epigenetic modifications of the GNAQ gene. In this study, we examined the expression and epigenetic changes of GNAQ in the hypothalamus in ovariectomized and estradiol-treated (OVX+E2) sheep under three photoperiod treatments (short photoperiod treatment for 42 days, SP42; long photoperiod treatment for 42 days, LP42; 42 days of short photoperiod followed by 42 days of long photoperiod, SP-LP42). The results showed that the expression of GNAQ was significantly higher in SP-LP42 than in SP42 and LP42 (p < 0.05). Whole genome methylation sequencing (WGBS) results showed that there are multiple differentially methylated regions (DMRs) and loci between different groups of GNAQ. Among them, the DNA methylation level of DMRs at the CpG1 locus in SP42 was significantly higher than that of SP-LP42 (p < 0.01). Subsequently, we confirmed that the core promoter region of the GNAQ gene was located with 1100 to 1500 bp upstream, and the DNA methylation level of all eight CpG sites in SP42 was significantly higher than those in LP42 (p < 0.01), and significantly higher than those in SP-LP42 (p < 0.01), except site 2 and site 4 in the first sequencing fragment (p < 0.05) in the core promoter region. The expression of acetylated GNAQ histone H3 was significantly higher than that of the control group under three different photoperiods (p < 0.01); the acetylation level of sheep hypothalamic GNAQ genomic protein H3 was significantly lower under SP42 than under SP-LP42 (p < 0.05). This suggests that acetylated histone H3 binds to the core promoter region of the GNAQ gene, implying that GNAQ is epigenetically regulated by photoperiod through histone acetylation. In summary, the results suggest that photoperiod can induce DNA methylation in the core promoter region and histone acetylation in the promoter region of the GNAQ gene, and hypothesize that the two may be key factors in regulating the differential expression of GNAQ under different photoperiods, thus regulating the hypothalamus-pituitary-gonadal axis (HPGA) through the seasonal estrus in sheep. The results of this study will provide some new information to understand the function of epigenetic modifications in reproduction in sheep.

Minipuberty in Sons of Women with Low Vitamin D Status during Pregnancy.

Minipuberty is a transient phase of reproductive axis activation during the first several months of life, playing an important role in the development of reproductive organs in boys. Low 25-hydroxyvitamin D levels during pregnancy are associated with an increased risk of neonatal complications. An inadequate gestational vitamin D status is hypothesized to affect the postnatal activation of the hypothalamic-pituitary-gonadal axis. The purpose of our study was to assess whether a low vitamin D status during pregnancy determines the course of minipuberty in boys. The study included three groups of male infants born to women with different vitamin D statuses: sons of women with vitamin D deficiency (group 1), sons of women with vitamin D insufficiency (group 2), and male offspring of females with normal 25-hydroxyvitamin D levels (group 3 (the reference group)). Concentrations of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone in saliva, as well as concentrations of gonadotropins in urine, were assayed monthly from postnatal months 1 to 6, and once every 2 months in the second half of the first year of life. Additionally, at each visit, penile length and testicular volume were assessed. Concentrations of testosterone, FSH, and LH, as well as penile length and testicular volume, were greater in group 1 than in groups 2 and 3. In turn, group 2 was characterized by higher FSH levels and a greater testicular volume than group 3. Peak concentrations of LH and testosterone were observed earlier in group 1 than in the remaining groups. The obtained results suggest that a low vitamin D status during pregnancy may have a stimulatory impact on reproductive axis activity and on the early postnatal development of male genital organs, correlating with the severity of hypovitaminosis D.

Assessment of endocrine function in males with pre-diabetes

Introduction and Aim: Diabetes mellitus is associated with various endocrine derangements and prediabetes is an intermediate condition between health and full-fledged disease state. Hormones of Hypothalamus-Pituitary-Thyroid (HPT), Hypothalamus-Pituitary-Adrenal (HPA), Hypothalamus-Pituitary-Gonadal (HPG) axes and pineal gland were studied in males (n=105) with prediabetes.&#x0D; &#x0D; Materials and Methods: Based on fasting plasma glucose (FPG), the subjects were categorized as healthy controls, prediabetes, diabetes and various hormones were compared between these three groups.&#x0D; &#x0D; Results: Insulin levels showed a systematic increase from pre-diabetes to diabetes subjects. HPT axis had a semblance to “Primary hypothyroidism” with an increase in Thyrotropin-releasing-hormone (TRH), Thyroid-stimulating-hormone (TSH) and decrease in fT4 and fT3 with rise in glucose levels. HPA axis detected high Corticotropin Releasing Hormone (CRH), Adrenocorticotropic hormone (ACTH), cortisol in the overtly diabetic group while prediabetes values were comparable to control. The HPG axis demonstrated significantly high Gonadotropin-hormone-releasing-hormone (GnRH) in the diabetic group but not in the prediabetic. A graded increase in LH and significant decrease in testosterone and melatonin was observed with a rise in FPG.&#x0D; &#x0D; Conclusion: Thus, it could be concluded as endocrine gland damage due to hyperglycemia and hyperinsulinemia causes multiple endocrine dysfunctions in prediabetes that aggravates, as the patient turns diabetic.

405 The Effects of Disease-Induced Inflammation on Reproductive Neuroendocrinology: Evidence from Sheep

Abstract Reproduction is dictated by the cohesive functioning of the organs of the hypothalamic-pituitary-gonadal (HPG) axis. As the name suggests, reproduction starts within the hypothalamus through the production and pulsatile secretion of gonadotropin releasing hormone (GnRH) followed by subsequent secretion of luteinizing hormone (LH) from the anterior pituitary and then steroidogenesis and gametogenesis in the gonads. Additionally, the HPG axis is tightly regulated by internal and external cues and, over the last twenty years, kisspeptin has been identified as a key modulator for reproduction through its stimulatory actions on GnRH neurons to secrete GnRH and subsequently LH. Growing evidence indicates that these kisspeptin expressing neurons are negatively affected by stressors (e.g., inflammation, social stress, metabolic stress) resulting in impaired reproduction. Inflammation caused by lipopolysaccharide (LPS, endotoxin), a component of the cell membrane of Gram-negative bacteria (e.g., Escherichia coli), is of particular interest due to its relationship with common livestock ailments, such as mastitis and metritis, and its suppression of GnRH and LH secretions. However, there is limited information about the influence disease-induced inflammation has on kisspeptin expressing neurons. In rats, acute endotoxin inflammation will cause about a 50% decrease in the number of kisspeptin immunopositive cells in the arcuate nucleus along with a suppression in LH secretion. In ewes, an acute dose will decrease the proportion of activated kisspeptin neurons in the ARC and POA. However, the mechanisms by which inflammation affects reproduction are not completely understood, especially in domestic livestock. Through a series of experiments, we aim to elucidate these mechanisms and effects of endotoxinemia in both an acute and a chronic model. To accomplish these goals, we administered endotoxin acutely to ewes. Overall, the suppression of LH secretion at the level of hypothalamus is possible, however, more research is required to further elucidate the mechanism. To evaluate a chronic model of systemic inflammation, we evaluated routes of endotoxin administration by randomly assigning twenty two castrated male sheep into one of five groups - control (CON), single acute IV dose (SAD; 400 ng/kg BW LPS) administered on Day 1, daily acute IV dose (DAD; 400 ng/kg BW LPS), daily increasing IV dose (DID; starting with 400 ng/kg BW LPS and increasing 20% each day), or steady subcutaneous dose (SSD; 20 µg/kg BW LPS over 24 hours), all administered during a one-week study period. Chronic inflammation, induced by a daily rising dose of IV administered LPS, suppresses LH secretion through effects on kisspeptin protein expression in the middle arcuate nucleus of the hypothalamus of sheep. Taken together, systemic inflammation associated with infection and disease likely impairs reproduction in part through suppression of kisspeptin-expressing neurons.

Life cycle exposure to 2-phenylbenzimidazole-5-sulfonic acid disrupts reproductive endocrine system and induces transgenerational adverse effects in zebrafish

Global attention has been focused on organic UV filters due to their ubiquity and potential damage to aquatic environment, yet the effects of their life cycle exposure on fish reproduction remain unknown. In the present study, the influence of 2-phenylbenzimidazole-5-sulfonic acid (PBSA) exposure on the reproductive endocrine system of zebrafish was examined, from 6 hours post fertilization (hpf) until 150 days, at levels that near-environmentally relevant (0 to 20 μg/L). Our results showed that exposure to PBSA at 20 μg/L caused a slight decrease in the Gonadosomatic Index (GSI) of female zebrafish in the F0 generation. Furthermore, this exposure had a negatively effect on reproduction, accompanied by delayed oocyte maturation, reduced cumulative egg production and decreased fertilization rate. Additionally, offspring embryos displayed reduced egg diameter at 0.75 hpf, delayed cumulative hatching rate at 60 hpf, and increased deformities rate at 72 hpf, indicating an adverse transgenerational effect. Moreover, PBSA exposure was associated with decreased plasma levels of sex hormones of 17β-estradiol (E2) and 11-ketotestosterone (11-KT), as well as altered the transcriptional profiles of certain genes in the HPG (hypothalamic–pituitary–gonadal) and liver axis. Molecular docking (MD) simulations revealed that specific amino acid residues of PBSA interact with zebrafish estrogen receptors, confirming its xenoestrogenic properties. Therefore, exposure to PBSA during its life cycle can disturb fish reproduction through endocrine disruption, thus necessitating strict environmental regulations for the disposal of UV filters to protect ecological and public health.

Effect of Piperine on Hypothalamic Pituitary Gonadal Axis of Female Albino Rats - A Probable Cause of PCOS

Background: Piperine is a constituent of black pepper. When administered to female adult albino rats, it results in increased levels of LH and FSH, and thus causing diminished ability to procreate.&#x0D; Aim: Is determining the deleterious piperine influences on LH and FSH levels of adult female albino rats.&#x0D; Study design: It is Experimental&#x0D; Location and experiment span: Deptt. of Anatomy, FPGMI, Lahore extending from 01-08-13 to 31-01-14&#x0D; Methodology: By random selection from 30 rats, three equal groups were made, each with 10 animals. Control status was assigned to group A which was not given any medicine, but only N/S administered with the dosage 10ml/kg body wt./day by using NG tube for a span of 30 days. Group B was given piperine at dosage of 5mg/kg/day for a period of thirty days. The C group was administered drug at the dosage of 10mg per kg per day for the same period of time as A and B via the same route. At completion of thirty days of the study, the animals of the 3 groups were given euthanasia. Dissection was performed, their ovaries were removed, and after that fixed in 10% formalin. Then, 4-5 micrometer sections preparation was done by using the microtome and then H&amp;E staining was carried out. &#x0D; Results: FSH and LH levels in serum of group B rats was shown to have increased in comparison to control group A. The FSH and LH levels in rats of C group was greater than that in rats of B group. When the two groups were compared, this difference was determined to be extremely of significance having a p-value less than 0.001. &#x0D; &#x0D; Conclusion: Giving Piperine to female adult albino rats was shown to cause significant increase in levels of FSH and LH which is likely to produce negative feedback on hypothalamic-pituitary-gonadal axis and in this way hamper female fertility during their productive years probably by causing PCOS.&#x0D; Key words: Piperine, Albino rat, ovaries, LH, FSH, fertility, hypothalamic-pituitary-gonadal axis, PCOS &#x0D;

Expression of Apelin and Apelin Receptor Protein in the Hypothalamo-Pituitary-Ovarian Axis during the Estrous Cycle of Mice

Plain Language SummaryIn the current study, we explore the presence of apelin and its receptor in hypothalamus, pituitary, and ovary of mice during estrous cycle. Apelin system changes at different level of reproductive axis during reproductive phase of female mice. Apelin inhibits gonadotropin secretion from pituitary. During the estrous cycle, the apelin system’s pattern changed in a tissue-dependent manner along the HPO axis. According to our research and evidence from earlier studies, apelin may have an inhibitory effect on pituitary and hypothalamic activities and a stimulatory effect on ovarian function.

Central precocious puberty secondary to peripheral precocious puberty due to a pineal germ cell tumor: a case and review of literature

BackgroundThe pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic–pituitary–gonadal axis. Germ cell tumor secreting human chorionic gonadotropin is a rare cause of peripheral puberty.Case presentationA 5.8-year-old male presented facial hair and phallic growth, deepened voice, and accelerated growth velocity for 6 months. The elevated human chorionic gonadotropin level with undetectable gonadotropin levels indicated peripheral precocious puberty. Brain imaging revealed a pineal mass and further pathology indicated the diagnosis of teratoma. During chemoradiotherapy with operation, the elevated human chorionic gonadotropin level reduced to normal range, while the levels of gonadotropins and testosterone increased. Subsequently, progressing precocious puberty was arrested with gonadotrophin-releasing hormone analog therapy. Previous cases of transition from peripheral precocious puberty to central precocious puberty were reviewed. The transitions were caused by the suddenly reduced feedback inhibition of sex steroid hormones on gonadotropin releasing hormone and gonadotropins.ConclusionsFor patients with human chorionic gonadotropin-secreting tumors, gonadotropin levels increase prior to sex steroid decrease, seems a sign of melatonin-related central PP related to melatonin.