The cycle of stress: A systematic review of the impact of chronic psychological stress models on the rodent estrous cycle.

Stress is known to impair reproduction through interactions between the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. However, while it is well accepted that stress can alter estrous cycle regularity, a key indicator of female's HPG axis function, effects of different types of psychological stress have been inconsistent. This systematic review evaluated the impact of rodent models of psychological stress on estrous cyclicity, while reporting biological parameters pertaining to HPA or HPG axis function assessed within these studies. We performed a systematic database search and included articles that implemented a psychological stress model in rodents and reported estrous cyclicity for at least two cycles after initiation of stress. Of the 32 studies included, 62.5% reported post-stress alterations to estrous cyclicity, with Chronic Mild Stress (CMS) models showing the most conclusive effects. Twenty-five studies measured HPG or HPA axis markers, with cycle disruptions being commonly observed in parallel with altered estradiol and increased corticosterone levels. Our review highlights gaps in reporting estrous cyclicity assessments and makes recommendations to improve comparability between studies.

Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption.

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

Metabolic hormones are integral regulators of female reproductive health and function.

The female reproductive system is strongly influenced by nutrition and energy balance. It is well known that food restriction or energy depletion can induce suppression of reproductive processes, while overnutrition is associated with reproductive dysfunction. However, the intricate mechanisms through which nutritional inputs and metabolic health are integrated into the coordination of reproduction are still being defined. In this review, we describe evidence for essential contributions by hormones that are responsive to food intake or fuel stores. Key metabolic hormones-including insulin, the incretins (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1), growth hormone, ghrelin, leptin, and adiponectin-signal throughout the hypothalamic-pituitary-gonadal axis to support or suppress reproduction. We synthesize current knowledge on how these multifaceted hormones interact with the brain, pituitary, and ovaries to regulate functioning of the female reproductive system, incorporating in vitro and in vivo data from animal models and humans. Metabolic hormones are involved in orchestrating reproductive processes in healthy states, but some also play a significant role in the pathophysiology or treatment strategies of female reproductive disorders. Further understanding of the complex interrelationships between metabolic health and female reproductive function has important implications for improving women's health overall.

The prolactin receptor gene (PRLR) is linked and associated with the risk of polycystic ovarian syndrome.

The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results.

The roles of anti-Müllerian hormone in breast cancer.

Anti-Müllerian hormone (AMH) is produced and secreted by granulosa cells of growing follicles, and its main role is to inhibit the recruitment of primordial follicles, reduce the sensitivity of follicles to follicle-stimulating hormone (FSH), and regulate FSH-dependent preantral follicle growth. It has become an effective indicator of ovarian reserve in clinical practice. Research on AMH and its receptors in recent years has led to a better understanding of its role in breast cancer. AMH specifically binds to anti-Müllerian hormone receptor II (AMHRII) to activate downstream pathways and regulate gene transcription. Since AMHRII is expressed in breast cancer cells and triggers apoptosis, AMH/AMHRII may play an important role in the occurrence, treatment, and prognosis of breast cancer, which needs further research. The AMH level is a potent predictor of ovarian function after chemotherapy in premenopausal breast cancer patients older than 35 years, either for ovarian function injury or ovarian function recovery. Moreover, AMHRII has the potential to be a new marker for the molecular typing of breast cancer and a new target for breast cancer treatment, which may be a link in the downstream pathway after TP53 mutation.

Interacting Networks of the Hypothalamic-Pituitary-Ovarian Axis Regulate Layer Hens Performance.

Egg production is a vital biological and economic trait for poultry breeding. The 'hypothalamic-pituitary-ovarian (HPO) axis' determines the egg production, which affects the layer hens industry income. At the organism level, the HPO axis is influenced by the factors related to metabolic and nutritional status, environment, and genetics, whereas at the cellular and molecular levels, the HPO axis is influenced by the factors related to endocrine and metabolic regulation, cytokines, key genes, signaling pathways, post-transcriptional processing, and epigenetic modifications. MiRNAs and lncRNAs play a critical role in follicle selection and development, atresia, and ovulation in layer hens; in particular, miRNA is known to affect the development and atresia of follicles by regulating apoptosis and autophagy of granulosa cells. The current review elaborates on the regulation of the HPO axis and its role in the laying performance of hens at the organism, cellular, and molecular levels. In addition, this review provides an overview of the interactive network regulation mechanism of the HPO axis in layer hens, as well as comprehensive knowledge for successfully utilizing their genetic resources.

Secretion of reproductive hormones and estrous cycle in rats interfered by combined exposure to beta-cypermethrin and emamectin benzoate / 环境与职业医学

Backgroud Beta-cypermethrin and emamectin benzoate are widely used for the prevention and control of pests in the greenhouse planting industry, and their combined exposure may increase the accumulation of beta-cypermethrin and emamectin benzoate in organisms and affect human health. Objective Based on the changes in reproductive hormone levels in the hypothalamic-pituitary-ovarian (HPO) axis, to investigate the effect of combined exposure to beta-cypermethrin and emamectin benzoate on the estrous cycle of female mice. Methods Twenty-four healthy adult SD rats were randomly divided into a blank control group, a beta-cypermethrin group (Beta-CYP, 53 mg·m−3), an emamectin benzoate group (EMB, 8 mg·m−3), and a beta-cypermethrin and emamectin benzoate combined exposure group (Beta-CYP+EMB, Beta-CYP 53 mg·m−3 + EMB 8 mg·m−3). Six rats in each group were exposed to the designed treatment protocol by aerosol inhalation 6 d a week for 13 weeks. The general condition of the rats was observed in real time during the treatment. From the 12th week of exposure, a 10-day reproductive tract smear was performed on the rats to observe the estrous cycle. The rats were neutralized on the second day after the end of the treatment protocol, and the ovarian tissues were stained with HE to observe histopathological changes. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured by ELISA. Experimental results were expressed as mean ± standard deviation (\begin{document}$ \overline{x}\pm s $\end{document}). One-way ANOVA was used for comparison among groups, and LSD test for pairwise comparison between groups. The significance level was α=0.05. Results After four weeks of the treatment protocol, the rats in the Beta-CYP group and the Beta-CYP+EMB group continued to be hyperactive and irritable, while the EMB group showed symptoms of mental disorder, decreased activity, and slow response. On the 90th day of the treatment protocol, the body weight of rats in the control group increased to (314.51±2.44) g, and that in the Beta-CYP+EMB group only increased to (253.47±1.50) g. There was no abnormal cellular morphology in the control group; however, small deeply stained nuclei appeared in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group, and abnormal morphological development of keratinized epithelial cells in the Beta-CYP+EMB group was found. The estrous cycle of rats in the control group was (97.83±4.17) h, and compared with the control group, the estrous cycles of rats in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group were prolonged to (134.33±7.53) h, (126.50±5.28) h, and (156.00±6.66) h, respectively. The results of ANOVA showed that the numbers of leukocytes (527.17±15.83), keratinized epithelial cells (35.67±4.32), and non-keratinized epithelial cells (70.50±4.51) in the vaginal smears during diestrus in the Beta-CYP+EMB group were significantly lower than those in the control group (752.50±28.89, 50.50±2.74, 101.33±7.92) (P<0.001). The hormone levels of GnRH and FSH in the control group were (5.13±0.59) and (0.76±0.09) IU·L−1 respectively, while the levels in the Beta-CYP+EMB group were increased to (16.86±0.59) and (3.80±0.19) IU·L−1 respectively (P<0.05). The levels of LH and E2 in the control group were (12.93±0.81) IU·L−1 and (22.23±1.44) pmol·L−1 respectively, and the levels in the Beta-CYP+EMB group were decreased to (5.63±0.41) IU·L−1 and (10.45±0.78) pmol·L−1 respectively (P<0.05). Conclusion The combined exposure to beta-cypermethrin and emamectin benzoate may ultimately affect the estrous cycle of female rats by interfering with the secretion of reproductive hormones involved in the HPO axis.

[Effects of nutritional preparation on HPO axis function and energy metabolism in uterus and ovary of rats exposed to intermittent cold].

Objective: To investigate the effects of a self-designed nutritional preparation on hypothalamic-pituitary-ovarian (HPO) axis function and energy metabolism in female SD rats exposed to intermittent cold. Methods: Female SD rats were divided into control group, cold exposure group and nutritional preparation group. The control group and cold exposure group were given distilled water by daily gavage, and the nutritional preparation group was given nutritional preparation intragastrically. After the treatment, the cold exposure group and nutritional preparation group were exposed to -10℃ in a cabin for 4 h every day. After being treated for 14 days, the serum, uterus and ovary of rats were collected. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and other hormone indicators were detected by enzyme-linked immunosorbent assay (ELISA) and colorimetry was used to detect ATPase and other energy metabolism related indicators. Results: Compared with the control group, cold exposure significantly up-regulated the protein expressions of FSHR and LHR, and notably enhanced the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in ovary and uterus (P<0.05). Nutritional preparation down-regulated the protein expressions of FSHR and LHR, and inhibited the activity of ATPase in ovary and uterus (P<0.05) compared with the cold exposure group. Conclusion: Nutritional preparations can effectively improve the expressions of HPO axis related receptors and abnormal energy metabolism in uterus and ovary caused by intermittent cold exposure.

Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction.

BACKGROUND: Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. MAIN TEXT: Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. CONCLUSION: More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

Hypothalamic mechanisms of obesity-associated disturbance of hypothalamic-pituitary-ovarian axis.

Ovulatory disorders are the most common clinical feature exhibited among obese women. Initiation of ovulation physiologically requires a surge of gonadotropin-releasing hormone (GnRH) released from GnRH neurons located in the hypothalamus. These GnRH neurons receive metabolic signals from circulation and vicinal neurons to regulate GnRH release. Leptin acts indirectly on GnRH via adjacent leptin receptor (LEPR)-expressing neurons such as proopiomelanocortin (POMC), neuropeptide Y (NPY)/agouti-related peptide (AgRP), and neuronal nitric oxide (NO) synthase (nNOS) neurons to affect GnRH neuronal activities. Additionally, hypothalamic inflammation also affects ovulation independent of obesity. Therefore, this review focuses on hypothalamic mechanisms that underlie the disturbance of hypothalamic-pituitary-ovarian (HPO) axis during obesity with an attempt to promote future studies and/or novel therapeutic strategies for ovulatory disorders in obesity.

An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis.

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant-like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

[Effect of electroacupuncture on expression of Kisspeptin protein in hypothalamus of rats with polycystic ovary syndrome].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of Kisspeptin protein and activities of the hypothalamic-pituitary-ovarian axis(HPOA) in rats with Letrozole-induced polycystic ovary syndrome (PCOS). METHODS: Female SD rats were randomly divided into normal control, PCOS model and EA groups (n=6 rats in each group). The PCOS model was established by continuous gavage of letrozole for 21 d. EA(2 Hz/100 Hz, 0.6-1.4 mA) was applied to bilateral "Daimai" (GB26) for 20 min, once every day for 15 d. Body mass was measured every 4 days. Serum follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and testosterone (T) were detected by radioimmunoassay. Histopathological changes of the ovarian were observed after H.E. staining, and the expression level of Kisspeptin protein in the hypothalamus was detected by Western blot. RESULTS: Following modeling, the body mass, serum T and LH contents, hypothalamic Kisspeptin protein expression and the number of ovarian follicles were significantly increased (P<0.05, P<0.01), while the number of ovarian corpus luteum was apparently decreased in comparison with the normal group (P<0.01). After EA intervention, the serum T, LH and E2 contents, the expression of Kisspeptin protein and the number of ovarian follicles were notably down-regulated (P<0.05, P<0.01), and the number of corpus luteum was significantly increased (P<0.01) in comparison with the model group. CONCLUSION: EA can regulate the levels of sex hormones and HPOA of PCOS rats, which may be related to its effect in down-regulating the expression of Kisspeptin protein in the hypothalamus.

Zihuai recipe alleviates cyclophosphamide-induced diminished ovarian reserve via suppressing PI3K/AKT-mediated apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zihuai recipe (ZHR), a Chinese herbal prescription, is widely used for the clinical treatment of Diminished ovarian reserve (DOR) infertility. However, little is known regarding its underlying mechanisms of DOR treatment. AIM OF THE STUDY: This study aimed to investigate the beneficial effects of ZHR on the treatment of DOR and to reveal the underlying mechanisms. MATERIALS AND METHODS: Sixty female 8-week-old Sprague-Dawley rats were randomly divided into the following six groups (n=10 per group): control, DOR, low-dose(2.7 g/kg/day) ZHR (L-ZHR), medium-dose(5.4 g/kg/day), ZHR (M-ZHR), high-dose(10.8 g/kg/day) ZHR (H-ZHR), and hormone replacement therapy (HRT) treatment groups. The DOR model was established in all the groups, except the control group, by a single intraperitoneal injection of 90 mg/kg cyclophosphamide. After the induction of the DOR model, rats were weighed and administered either the relevant dose of ZHR or an equal volume of saline solution (in the control and DOR groups). Rats in the HRT group received estradiol valerate tablets (0.16 mg/kg/day), and with medroxyprogesterone acetate tablets (0.86 mg/kg/day) added on day 4. After 32 days of treatment, the rats were euthanized and the ovaries were collected for sampling. Ovarian morphology was observed by hematoxylin and eosin staining and the number of follicles was counted under a microscope. The serum levels of anti-Müllerian hormone (AMH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were quantified by ELISA. A TUNEL assay was used to analyze the level of apoptosis of the ovarian cells. The protein expressions of p-PI3K, p-AKT, PI3K, AKT, cleaved caspase-3, BAX, and Bcl-2 were measured by western blotting and immunohistochemistry. Data analysis was performed with SPSS 20.0 software. RESULTS: ZHR administration increased the ovarian index and the serum levels of AMH, GnRH, and E2, while lowering those of FSH and LH. ZHR treatment also increased the number of primordial, primary, secondary, and antral follicles, as well as the number of corpora lutea, but decreased the number of atretic follicles. Furthermore, ZHR administration decreased the percentage of TUNEL-positive ovarian cells. After treatment with ZHR, the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, cleaved caspase-3 and BAX were decreased, whereas the level of Bcl-2 was increased. CONCLUSIONS: ZHR improved the ovarian reserve in CTX-induced DOR rats. The mechanisms of ZHR on DOR may be mediated through the regulation of gonadal hormones of the hypothalamic-pituitary-ovarian axis (HPOA), and the inhibition of PI3K/AKT-mediated apoptosis in granulosa cells.

Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7,8-dihydroxyflavone in female mice.

OBJECTIVE: 7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. METHODS: For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro, the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. RESULTS: Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. CONCLUSIONS: These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women.

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis.

Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%-13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic-pituitary-ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

Effects of glyphosate-based herbicide-contaminated diets on reproductive organ toxicity and hypothalamic-pituitary-ovarian axis hormones in weaned piglets.

At present, glyphosate (GLP) is the most produced and used herbicide in the world. With the large-scale use of glyphosate-based herbicides (GBHs), their toxic effects on animals and plants have increasingly become a concern. Based on the Codex Alimentarius Commission (CODEX) dose (20 mg kg-1) and the dose set by the government (40 mg kg-1), four experimental groups in which Roundup® (R) herbicide was added to the feed of weaned piglets at GLP concentrations of 0, 10, 20, and 40 mg kg-1 were designed. The results showed that R had no significant effect on the vulvar size or index of reproductive organs but that it could affect the tissue morphology and ultrastructure of the uterus and ovary. With the increase in GLP concentration, the activities of antioxidant enzymes [SOD (P < 0.05) and GPx (P = 0.002)] in the uterus showed significant increases. Compared with the control group, the content of hydrogen peroxide (H2O2) in the treatment groups increased significantly (P < 0.05), the malondialdehyde (MDA) content in the 10 mg kg-1 treatment group was significantly higher than that in the control group. We measured hypothalamic-pituitary-ovarian axis (HPOA) hormones and also found that GLP significantly increased luteinizing hormone-releasing hormone (LHRH), gonadotropin-releasing hormone (GnRH) and testosterone (T) content (P < 0.05) and decreased follicle-stimulating hormone (FSH) content (P < 0.05). In summary, although R does not affect the vulvar size or reproductive organ index of weaned piglets, it changes the morphology and ultrastructure of the uterus and ovaries, interferes with the synthesis and secretion of HPOA hormones, and causes changes in the balance of the antioxidant system of uterus. This study provided a theoretical basis for preventing reproductive system harm caused by GBHs.

[Effects of repeated immobilization stress on hypothalamic-pituitary- ovarian axis in female rats].

Objective: To explore the effects of repeated immobilization stress on hypothalamic-pituitary-ovarian axis in female rats. Methods: Forty female SD rats were randomly divided into two groups: control group (n=20) and experimental group (n=20). One group was fed normally, the other group was subjected to incremental load restraint stress. Brake stress once a day in the retainer (starting at 9: 00 a.m.), braking for 2 hours on the first day, increasing load by 0.5 hours a day for two weeks. Body weight, estrous cycle, sex hormone, organ coefficient, pathology and expression of related genes were detected to explore the harm of hypothalamic-pituitary-ovarian axis. Results: Repeated immobilization stress caused weight loss, prolonged estrous cycle, and changed the organ coefficient and morphology of ovaries and uterus. QPCR technique was used to detect the related genes. It was found that the expressions of gonadotropin releasing hormone, pituitary gonadotropin releasing hormone receptor, follicle stimulating hormone and luteinizing hormone mRNA were decreased significantly, while the expressions of ovarian follicle stimulating hormone and luteinizing hormone receptor mRNA were increased significantly. The expression of estrogen receptor mRNA in ovary and uterus was decreased significantly. Conclusion: Repeated immobilization stress may disrupt the estrous cycle by interfering with the endocrine regulation of the hypothalamic-pituitary-ovarian axis, thus damaging the gonadal and reproductive endocrine function of female animals.

[Comparison and analysis of lincRNAs expression profile in the hypothalamic-pituitary-ovarian axis of anestrous and estrous primiparous sows].

The normal estrus in weaned primiparous sows has a great impact on pig production and abnormal estrus is the main reason for the elimination of primiparous sows. In this study, we studied the long intergenic noncoding RNAs (lincRNAs) in the hypothalamic-pituitary-ovarian axis of anestrous and estrous primiparous sows. These long intergenic noncoding RNAs (lincRNAs) were screened and compared through RNA-seq analysis. The expression profiles of lincRNAs were obtained and their characteristics and functions were preliminarily analyzed. There are 3519 novel lincRNAs identified in the hypothalamic-pituitary-ovarian axis of anestrous and estrous primiparous sows. Compared with estrous primiparous sows, 17 differentially expressed lincRNAs were indentified, including 12 up-regulated lincRNAs and 5 down-regulated lincRNAs (FC≥2, P<0.05). The four lincRNA transcripts obtained through selection were verified by qRT-PCR, which are consistent with the RNA-seq results. The GO, KEGG pathway, and lincRNA-mRNA co-expression network analysis of these 17 lincRNAs revealed that these lincRNAs were mainly involved in reproductive activities, such as oocyte meiosis mature, ovarian cells differentiation and granulosa cells apoptosis. The results enriched the data resources of pig lincRNAs and provided useful information for further research about the reproductive performance of primiparous sows.

Effects of repeated immobilization stress on hypothalamic-pituitary- ovarian axis in female rats / 中国应用生理学杂志

To explore the effects of repeated immobilization stress on hypothalamic-pituitary-ovarian axis in female rats. Methods: Forty female SD rats were randomly divided into two groups: control group (n=20) and experimental group (n=20). One group was fed normally, the other group was subjected to incremental load restraint stress. Brake stress once a day in the retainer (starting at 9: 00 a.m.), braking for 2 hours on the first day, increasing load by 0.5 hours a day for two weeks. Body weight, estrous cycle, sex hormone, organ coefficient, pathology and expression of related genes were detected to explore the harm of hypothalamic-pituitary-ovarian axis. Repeated immobilization stress caused weight loss, prolonged estrous cycle, and changed the organ coefficient and morphology of ovaries and uterus. QPCR technique was used to detect the related genes. It was found that the expressions of gonadotropin releasing hormone, pituitary gonadotropin releasing hormone receptor, follicle stimulating hormone and luteinizing hormone mRNA were decreased significantly, while the expressions of ovarian follicle stimulating hormone and luteinizing hormone receptor mRNA were increased significantly. The expression of estrogen receptor mRNA in ovary and uterus was decreased significantly. Repeated immobilization stress may disrupt the estrous cycle by interfering with the endocrine regulation of the hypothalamic-pituitary-ovarian axis, thus damaging the gonadal and reproductive endocrine function of female animals.