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Background: The hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females. Methods: We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum. Results: We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males', but in the last trimester of pregnancy, male components were more related to each other than female's. Conclusions: This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development. Highlights: This study is the first to analyze HPA and HPG axes receptors, peptides, and enzyme mRNA expression levels in the brains of fetuses in the wild. Higher HPA and HPG axes receptors mRNA expression levels in females hint towards alternative sex-specific mechanisms that regulate endocrine axes during fetal development. Coordination of HPA and HPG axes components' expression levels is different between males and females at different stages of gestation. Plain language summary: In litter-bearing mammals, the positioning of a fetus in the uterus relative to other fetuses of the same or opposite sex has been shown to directly influence fetal morphology and physiology, and later behavior, reproductive success, and survival in adults. In this study, we sought to understand the mechanisms by which the location in the uterus influences two major neuroendocrine pathways in fetal brains. We quantified expression of multiple receptors and an enzyme (referred to as 'components') of the endocrine axes in three different brain regions in fetal free-ranging nutrias. Our results showed higher expression in females than in males for some endocrine axes components. The location inside the uterus was also related to the expression of some components. Lastly, coordination between the axes was higher earlier on in gestation, and females were more coordinated than males in the second trimester, whereas males were more coordinated than females in the third trimester. The results of this study point to the mechanisms by which the sexes regulate key neuroendocrine pathways during fetal development. [ABSTRACT FROM AUTHOR]

Abstract Background The hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females. Methods We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum. Results We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males’, but in the last trimester of pregnancy, male components were more related to each other than female’s. Conclusions This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.

Vast stretches of open water bodies are gradually becoming hypoxic as a result of depletion of oxygen levels mainly due to various human anthropogenic activities. This problem of hypoxic stress on the fish population is likely to be exacerbated soon since the aquatic hypoxic environment is continuously spreading over vast areas worldwide. In recent years, various harmful effects of hypoxia to bony fishes have been reported, such as the restriction of energy-consuming metabolic processes, arrest of the growth of ovary and testes that are associated with endocrine disruption, loss of sperm and egg quality, inhibition of fertilization, hatching success, and also the reduction of larval survivability, thereby impairment of overall reproductive and developmental processes in fish. Disruption of the brain-pituitary-gonad axis, and certain enzymes related to steroidogenesis and vitellogenesis in fish have also been reported as the primary targets for an endocrine malfunction during hypoxia. Hypoxia-sensitive downregulation of key genes responsible for controlling sex hormones' synthesis has been documented in certain bony fishes. Further, continuous exposure to hypoxia was reported to induce early expression of pro-apoptotic/tumor suppressor p53 genes, thereby causing immense cell death in hypoxic embryos. However, the cellular responses to long-term hypoxia exposure and the degree of reproductive impairments in bony fishes are still not adequate to figure out the actual underlying mechanisms. The present review intends to highlight the current knowledge about the detrimental impact of chronic/acute hypoxia at different stages of fish reproduction and the associated underlying molecular mechanisms.

Background: Puberty marks the transition from childhood to adulthood and is initiated by activation of a pulsatile GnRH secretion from the hypothalamus. MKRN3 functions as a pre-pubertal break on the GnRH pulse generator and hypothalamic expression and circulating levels of MKRN3 decrease peripubertally. In rodents, microRNA miR-30b seems to directly target hypothalamic MKRN3 expression - and in boys, circulating levels of miR-30b-5p increase when puberty is pharmacologically induced. Similarly, miR-200b-3p and miR-155-5p have been suggested to inhibit expression of other proteins potentially involved in the regulation of GnRH secretion. Here we measure circulating levels of these three miRNAs as boys progress through puberty. Materials and Methods: Forty-six boys from the longitudinal part of the Copenhagen Puberty Study were included. All boys underwent successive clinical examinations including estimation of testis size by palpation. miR-30b-5p, miR-200b-3p, and miR-155-5p were measured in serum by RT-qPCR using a kit sensitive to the phosphorylation status of the miRNAs. Thirty-nine boys had miRNA levels measured in three consecutive samples (pre-, peri-, and postpubertally) and seven boys had miR-30b-5p levels measured in ten consecutive samples during the pubertal transition. Results: When circulating levels of miR-30b-5p in pre- and peri-pubertal samples were compared with post-pubertal levels, we observed a significant increase of 2.3 and 2.2-fold (p-value<6.0×10-4), respectively, and a larger fraction of miR-30b-5p appeared to be phosphorylated post-pubertally indicating an increase in its bioactivity. We also observed a negative correlation between circulating levels of miR-30b-5p and MKRN3. The inter-individual variation in circulating miR-30b levels was substantial and we could not define a clinical threshold for miR-30b-5p suggestive of imminent puberty. Also, miR-155-5p showed significantly increasing levels from the peri- to the post-pubertal stage (p=3.0×10-3), whereas miR-200b- 3p did not consistently increase. Conclusion: Both circulating levels of miR-30b-5p and its bioactivity increase during the pubertal transition in boys supporting its role in the activation of the HPG axis at the onset of physiologically normal puberty. [ABSTRACT FROM AUTHOR]

BackgroundPuberty marks the transition from childhood to adulthood and is initiated by activation of a pulsatile GnRH secretion from the hypothalamus. MKRN3 functions as a pre-pubertal break on the GnRH pulse generator and hypothalamic expression and circulating levels of MKRN3 decrease peri-pubertally. In rodents, microRNA miR-30b seems to directly target hypothalamic MKRN3 expression – and in boys, circulating levels of miR-30b-5p increase when puberty is pharmacologically induced. Similarly, miR-200b-3p and miR-155-5p have been suggested to inhibit expression of other proteins potentially involved in the regulation of GnRH secretion. Here we measure circulating levels of these three miRNAs as boys progress through puberty.Materials and MethodsForty-six boys from the longitudinal part of the Copenhagen Puberty Study were included. All boys underwent successive clinical examinations including estimation of testis size by palpation. miR-30b-5p, miR-200b-3p, and miR-155-5p were measured in serum by RT-qPCR using a kit sensitive to the phosphorylation status of the miRNAs. Thirty-nine boys had miRNA levels measured in three consecutive samples (pre-, peri-, and post-pubertally) and seven boys had miR-30b-5p levels measured in ten consecutive samples during the pubertal transition.ResultsWhen circulating levels of miR-30b-5p in pre- and peri-pubertal samples were compared with post-pubertal levels, we observed a significant increase of 2.3 and 2.2-fold (p-value

Vast stretches of open water bodies are gradually becoming hypoxic as a result of depletion of oxygen levels mainly due to various human anthropogenic activities. This problem of hypoxic stress on the fish population is likely to be exacerbated soon since the aquatic hypoxic environment is continuously spreading over vast areas worldwide. In recent years, various harmful effects of hypoxia to bony fishes have been reported, such as the restriction of energy-consuming metabolic processes, arrest of the growth of ovary and testes that are associated with endocrine disruption, loss of sperm and egg quality, inhibition of fertilization, hatching success, and also the reduction of larval survivability, thereby impairment of overall reproductive and developmental processes in fish. Disruption of the brain-pituitary-gonad axis, and certain enzymes related to steroidogenesis and vitellogenesis in fish have also been reported as the primary targets for an endocrine malfunction during hypoxia. Hypoxia-sensitive downregulation of key genes responsible for controlling sex hormones' synthesis has been documented in certain bony fishes. Further, continuous exposure to hypoxia was reported to induce early expression of pro-apoptotic/tumor suppressor p53 genes, thereby causing immense cell death in hypoxic embryos. However, the cellular responses to long-term hypoxia exposure and the degree of reproductive impairments in bony fishes are still not adequate to figure out the actual underlying mechanisms. The present review intends to highlight the current knowledge about the detrimental impact of chronic/acute hypoxia at different stages of fish reproduction and the associated underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Study questionDoes repeat-associated non-AUG (RAN) translation play a role in fragile X-associated primary ovarian insufficiency (FXPOI), leading to the presence of polyglycine containing protein (FMRpolyG)-positive inclusions in ovarian tissue?Summary answerOvaries of a woman with FXPOI and of an Fmr1 premutation (PM) mouse model (exCGG-KI) contain intranuclear inclusions that stain positive for both FMRpolyG and ubiquitin.What is known alreadyWomen who carry the FMR1 PM are at 20-fold increased risk to develop primary ovarian insufficiency (FXPOI). A toxic RNA gain-of-function has been suggested as the underlying mechanism since the PM results in increased levels of mRNA containing an expanded repeat, but reduced protein levels of fragile X mental retardation protein (FMRP). Recently, RAN translation has been shown to occur from FMR1 mRNA that contains PM repeat expansions, leading to FMRpolyG inclusions in brain and non-CNS tissues of fragile X-associated tremor/ataxia syndrome (FXTAS) patients.Study design, size, durationOvaries of a woman with FXPOI and women without PM (controls), and ovaries from wild-type and exCGG-KI mice were analyzed by immunohistochemistry for the presence of inclusions that stained for ubiquitin and FMRpolyG . The ovaries from wild-type and exCGG-KI mice were further characterized for the number of follicles, Fmr1 mRNA levels and FMRP protein expression. The presence of inclusions was also analyzed in pituitaries of a man with FXTAS and the exCGG-KI mice.Participants/materials, setting, methodsHuman ovaries from a woman with FXPOI and two control subjects and pituitaries from a man with FXTAS and a control subjects were fixed in 4% formalin. Ovaries and pituitaries of wild-type and exCGG mice were fixed in Bouin's fluid or 4% paraformaldehyde. Immunohistochemistry was performed on the human and mouse samples using FMRpolyG, ubiquitin and Fmrp antibodies. Fmr1 mRNA and protein expression were determined in mouse ovaries by quantitative RT-PCR and Western blot analysis. Follicle numbers in mouse ovaries were determined in serial sections by microscopy.Main results and the role of chanceFMRpolyG-positive inclusions were present in ovarian stromal cells of a woman with FXPOI but not in the ovaries of control subjects. The FMRpolyG-positive inclusions colocalized with ubiquitin-positive inclusions. Similar inclusions were also observed in the pituitary of a man with FXTAS but not in control subjects. Similarly, ovaries of 40-week-old exCGG-KI mice, but not wild-type mice, contained numerous inclusions in the stromal cells that stained for both FMRpolyG- and ubiquitin, while the ovaries of 20-week-old exCGG-KI contained fewer inclusions. At 40 weeks ovarian Fmr1 mRNA expression was increased by 5-fold in exCGG-KI mice compared with wild-type mice, while Fmrp expression was reduced by 2-fold. With respect to ovarian function in exCGG-KI mice: (i) although the number of healthy growing follicles did not differ between wild-type and exCGG-KI mice, the number of atretic large antral follicles was increased by nearly 9-fold in 40-week old exCGG-KI mice (P < 0.001); (ii) at 40 weeks of age only 50% of exCGG-KI mice had recent ovulations compared with 89% in wild-type mice (P = 0.07) and (iii) those exCGG-KI mice with recent ovulations tended to have a reduced number of fresh corpora lutea (4.8 ± 1.74 versus 8.50 ± 0.98, exCGG-KI versus wild-type mice, respectively, P = 0.07).Limitations, reasons for cautionAlthough FMRpolyG-positive inclusions were detected in ovaries of both a woman with FXPOI and a mouse model of the FMR1 PM, we only analyzed one ovary from a FXPOI subject. Caution is needed to extrapolate these results to all women with the FMR1 PM. Furthermore, the functional consequence of FMRpolyG-positive inclusions in the ovaries for reproduction remains to be determined.Wider implications of the findingsOur results suggest that a dysfunctional hypothalamic-pituitary-gonadal-axis may contribute to FXPOI in FMR1 PM carriers.Study funding/competing interestsThis study was supported by grants from NFXF, ZonMW, the Netherlands Brain Foundation and NIH. The authors have no conflict of interest to declare.

Cortisol inhibits hypothalamic-pituitary-gonadal (HPG) axis whereas RF9, a potent agonist of kisspeptin receptor (GPR54) activates HPG-axis during fasting-induced stress and under normal physiological conditions. However, the effect of RF9 on the cortisol-induced repressed HPG-axis is not studied yet. This study investigated whether exogenous cortisol-induced repression of the HPG-axis can be rescued by RF9. Six intact adult male rhesus monkeys (Macaca mulatta) habituated to chair-restraint were administered hydrocortisone sodium succinate at a rate of 20 mg/kg of body weight (BW) per day for 12 days. Single blood sample was taken by venipuncture from each animal on alternate days for hormones analyses. On experimental day 12, hydrocortisone treated monkeys received a single intravenous bolus of RF9 (n = 3) and vehicle (n = 3). The animals were bled for a period of 4 h at 60 min intervals from an indwelling cannula in the saphenous vein. RF9 was administered intravenously at the dose of 0.1 mg/kg BW immediately after taking 0 min sample. Plasma cortisol and testosterone concentrations were measured by using specific enzyme immunoassays. Hydrocortisone treatment increased plasma cortisol levels (P ≤ 0.0001) and decreased plasma testosterone (P ≤ 0.0127) levels. Interestingly, compared to vehicle, RF9 treatment significantly increased plasma testosterone levels at 120 min (P ≤ 0.0037), 180 min (P ≤ 0.0016), and 240 min (P ≤ 0.0001) intervals in the hydrocortisone treated monkeys. From these results, we concluded that RF9 administration relieves the suppressed HPG-axis in term of plasma testosterone levels in the cortisol treated monkeys.

Cortisol inhibits hypothalamic-pituitary-gonadal (HPG) axis whereas RF9, a potent agonist of kisspeptin receptor (GPR54) activates HPG-axis during fasting-induced stress and under normal physiological conditions. However, the effect of RF9 on the cortisol-induced repressed HPG-axis is not studied yet. This study investigated whether exogenous cortisol-induced repression of the HPG-axis can be rescued by RF9. Six intact adult male rhesus monkeys (Macaca mulatta) habituated to chair-restraint were administered hydrocortisone sodium succinate at a rate of 20 mg/kg of body weight (BW) per day for 12 days. Single blood sample was taken by venipuncture from each animal on alternate days for hormones analyses. On experimental day 12, hydrocortisone treated monkeys received a single intravenous bolus of RF9 (n = 3) and vehicle (n = 3). The animals were bled for a period of 4 h at 60 min intervals from an indwelling cannula in the saphenous vein. RF9 was administered intravenously at the dose of 0.1 mg/kg BW immediately after taking 0 min sample. Plasma cortisol and testosterone concentrations were measured by using specific enzyme immunoassays. Hydrocortisone treatment increased plasma cortisol levels (P ≤ 0.0001) and decreased plasma testosterone (P ≤ 0.0127) levels. Interestingly, compared to vehicle, RF9 treatment significantly increased plasma testosterone levels at 120 min (P ≤ 0.0037), 180 min (P ≤ 0.0016), and 240 min (P ≤ 0.0001) intervals in the hydrocortisone treated monkeys. From these results, we concluded that RF9 administration relieves the suppressed HPG-axis in term of plasma testosterone levels in the cortisol treated monkeys. [ABSTRACT FROM AUTHOR]

Paracetamol is one of the most widely sold non-prescription drugs. This study aimed to evaluate the effects of the paracetamol on reproductive, biochemical, genetic, histopathological and hematogical biomarkers by waterborne exposure. Male fish of Rhamdia quelen were exposed to environmental concentrations of paracetamol (0, 0.25, 2.5 μg/L) in a semi-static bioassay for 21 days. Hemoglobin and hematocrit were reduced upon exposure to 0.25 μg/L of paracetamol. Leukocytes and thrombocytes increased after paracetamol exposure. Paracetamol reduced testosterone levels in all exposed groups and increased estradiol levels at higher concentration. Serotonin and dopamine levels increased at exposure to 0.25 μg/L. Paracetamol also caused protein carbonyls and increased SOD activity in fish exposed to 2.5 μg/L and in addition led to an inhibition of EROD and GST activities in both concentrations. Hepatic genotoxicity occurred at the 0.25 μg/L concentration. Hepatic tissues of exposed fish showed mild blood congestion and leucocytes infiltration. The results showed that paracetamol disrupted the hypothalamic-pituitary-gonadal axis, changed hematological parameters and caused hepatotoxicity in Rhamdia quelen . The findings suggest that this drug merits attention relative to its potential endocrine disrupter effect and hepatotoxicity, even at concentrations found in the aquatic environment. [ABSTRACT FROM AUTHOR]

To study mechanisms underlying generalized effects of 3β hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exposed to trilostane at two dosages for 24, 48, or 96h and their gonadal RNA samples profiled with Agilent zebrafish microarrays. Trilostane had substantial impact on the transcriptional dynamics of zebrafish, as reflected by a number of differentially expressed genes (DEGs) including transcription factors (TFs), altered TF networks, signaling pathways, and Gene Ontology (GO) biological processes. Changes in gene expression between a treatment and its control were mostly moderate, ranging from 1.3 to 2.0 fold. Expression of genes coding for HSD3B and many of its transcriptional regulators remained unchanged, suggesting transcriptional up-regulation is not a primary compensatory mechanism for HSD3B enzyme inhibition. While some trilostane-responsive TFs appear to share cellular functions linked to endocrine disruption, there are also many other DEGs not directly linked to steroidogenesis. Of the 65 significant TF networks, little similarity, and therefore little cross-talk, existed between them and the hypothalamic–pituitary–gonadal (HPG) axis. The most enriched GO biological processes are regulations of transcription, phosphorylation, and protein kinase activity. Most of the impacted TFs and TF networks are involved in cellular proliferation, differentiation, migration, and apoptosis. While these functions are fairly broad, their underlying TF networks may be useful to development of generalized toxicological screening methods. These findings suggest that trilostane-induced effects on fish endocrine functions are not confined to the HPG-axis alone. Its impact on corticosteroid synthesis could also have contributed to some system wide transcriptional changes in zebrafish observed in this study. [Copyright &y& Elsevier]

Objective. Few studies are available on the temporal sequence and effect of ethnicity, socioeconomic status and environment on pubertal changes leading to sexual maturation in boys; therefore, we describe normative values for developmental changes in physical and endocrine characteristics at onset and during progression of the pubertal process in a cohort of Pakistani boys. Design. This cross-sectional study involved 234 healthy, 8-18 years old, school-based boys. Methods. Body weight, height, appearance of pubic hair patterns and testicular volume (TV) along with serum FSH, LH, testosterone and GH levels were measured. Results. Pubarche was first recorded at a mean age of 11.3 years [Tanner stage 2]. TV of 3 ml and the first significant increase in mean serum FSH and LH levels were detected at 10 years of age. The mean percent increase in TV/year was maximal from 12-14 years, coinciding with rising testosterone levels. The levels of gonadotropins increased more than 2-fold between 12-14 years. Whereas, LH continued to increase in postpubertal boys and FSH levels plateaued at 15 years. GH concentrations were shown to be maximal at 12-13 years and declined thereafter to prepubertal values. However, BW and height were significantly correlated with age; yet no significant correlation was seen between body mass index (BMI) and age. Conclusion. The present data among boys indicates an earlier transition to the Tanner stage 2 and an increase in TV, resulting in a slightly more extended period of pubertal development, as compared to European and American children pointing to ethnic, social and economic differences. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is becoming increasingly more prevalent worldwide and is a costly, devastating disease. The fact that females are more likely to be diagnosed with AD than men has contributed to the large amount of research and literature on estrogen's ability to rescue cognitive decline in aging females. However, recent results from the Women's Health Initiative Memory Study (WHIMS) and the Research into Memory, Brain Function and Estrogen Replacement (REMEMBER) study, in which estrogen-replacement therapy is shown not to be beneficial to cognition in postmenopausal women, especially in women of more advanced ages, have opened the study of hormones and hormone-based therapies beyond that of sex steroids. As such, recent findings, and the focus of this review, indicate that gonadotropins such as luteinizing hormone have a role on cognitive function and AD. It is likely that the interplay of age, and the timing of estrogen and these other less studied hormones will allow us to gain a better understanding of hypothalamic-pituitary-gonadal axis regulation after menopause and how it relates to AD, and will hopefully lead to new avenues of treatment for AD. [ABSTRACT FROM AUTHOR]

• Early life Hg exposure impairs reproduction in adult zebrafish. • Early life Hg exposure has intergenerational effect on reproduction of F 1 females. • Reproductive damage caused by early life Hg exposure is recovered in F 1 males. • Reproductive damage caused by early life Hg exposure is recovered in F 2 females. Mercury (Hg) is a global pollutant that poses potential threats to health of fishes. Although effects of Hg on reproduction of fishes have been documented, little is known about effects of exposure to Hg2+ during early life stages on subsequent reproductive fitness of adults or whether these effects can be transferred to offspring. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of Hg2+ (0.6, 3 or 15 μg/L) for 5 days and then depurated in clean water for another 115 days. Exposure to Hg2+ during early life stages disturbed the balance of sex hormones and gametogenesis by altering expression of mRNA for genes involved in the hypothalamic-pituitary-gonadal axis, which resulted in delayed gonadal development and lesser gonado-somatic index, thereby resulting in lesser fecundity. A similar, but less pronounced effect was observed in F 1 females that were not exposed directly to Hg, whereas such damage was neither observed in F 1 males nor either sex during the F 2 generation. Exposure to Hg2+ during early life can impair subsequent reproduction in adults and has intergenerational effects on F 1 females, but this reproductive damage can be recovered in F 1 males and in F 2 females. [ABSTRACT FROM AUTHOR]

This research explores the hypothalamus-pituitary-gonadal (HPG) axis activity for the control of spermatogenesis and quality sperm production. Topics covered include the characteristics of a primitive HPG in hagfish, review articles about the control of fetal and postnatal development of both Leydig and germ cells and the importance of antioxidant defenses, kisspeptins, estradiol, endocannabinoids and gonadotropin-releasing hormone (GnRH).