Serum Sex Hormone Levels Research Articles

Mediation of association between semen microcystin exposure and semen quality by sex hormones in Chinese men

Numerous studies have shown microcystins (MCs) inducing male reproductive toxicity, but the underlying mechanisms in humans are unclear. Therefore, this study aimed to evaluate the mediating role of serum sex hormones in the association between MC exposure and semen quality. In this study, we measured the levels of semen MCs and serum sex hormones in Chinese men [sample 1 (n = 649); sample 2 (n = 924)]. The results showed that there was a non-significant dose-dependent relationship between semen MCs and semen volume reduction (p for trend = 0.079) in sample 1, and semen MCs were significantly negatively associated with total motility, progressive motility, curvilinear velocity, mean angular displacement and acrosome integrity (p < 0.05) in sample 2. We also found that semen MCs were significantly positively associated with serum follicle stimulating hormone (FSH) (β = 0.151; 95% CI: 0.065, 0.236), but negatively associated with serum inhibin B (INHB) (β = −0.605; 95% CI: −0.944, −0.265), and these linear associations were confirmed in restricted cubic spline (RCS) models (all pnon-linearity > 0.1). Furthermore, mediation analysis revealed that serum INHB mediated 19.86% of the adverse effect of MC exposure on acrosome integrity. In conclusion, this study reveals the mediating roles of serum sex hormones in the relationship between MC exposure and decreased semen quality in men.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue

Ethnopharmacological relevanceAntler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong′s Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei′s Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. Aim of the studyThe Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. Materials and methodsSo the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I–V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. ResultsVinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. ConclusionVinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Effect of Ningxin-Yishen Formula on D-galactose-induced Premature Ovarian Insufficiency Mice by Inhibiting p53

: The prevalence of premature ovarian insufficiency (POI) is gradually increasing, safer and more effective treatments are urgently needed. The aim of this study was to evaluate the effects of Ningxin-Yishen formula (NXYSF) on D -galactose-induced POI mice as well as to shed a light on its potential mechanisms. : Six to eight weeks old C57BL/6 female mice were used in this study and randomly divided into six groups: control group; model group; estradiol valerate (EV) treatment group and NXYSF treatment group with graded doses (9.5, 19, and 38 g∙kg −1 /day). Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days. Afterwards, the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels. Furthermore, network pharmacology approach was performed to elucidate the potential targets of NXYSF, which were verified through western blotting experiments finally. : NXYSF could significantly reverse the inefficiency of weight gain caused by POI, and promote the development of primordial follicles. In addition, it could restore the abnormal serum anti-Müllerian hormone (AMH), estradiol (E 2 ), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Moreover, some crucial key gene targets including TP53 were proposed to be related with the effect of NXYSF through network pharmacology analysis. Last but importantly, western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovary. : Our findings proposed that NXYSF might be an effective alternative treatment for POI.

GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder

RationalePremenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD’s pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD. AimsThe aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms. MethodsParticipants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5β-THP; pregnenolone; 3α,5α-androsterone; 3α,5β-androsterone; 3α,5α-A-diol; 3α5β-A-diol; 3α,5α-THDOC; 3α5β-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment. ResultsParticipants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone. ConclusionsThis was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.

The amelioration of ovarian dysfunction by hesperidin in malathion-treated mice through the overexpression of PCNA and FSHR proteins

ObjectiveMalathion (MAL), a pesticide used for decades, is a highly toxic substance. Several studies have documented the negative effects of such agents on reproductive organ physiology, but the precise mechanism of action in the induction of ovarian dysfunction remains unclear. Therefore, the purpose of this research was to examine the effects of the antioxidant hesperidin (HES) on ovarian damage and toxicity caused by malathion. Materials and methodsIn this experiment, forty adult female bulb/c mice weighing 27–30 g were categorized into four groups, namely hesperidin (20 mg/kg, i.p.), malathion (3 mg/kg, i.p.), malathion + hesperidin, and control groups. Following a period of 35 consecutive days of treatment, mice were euthanized, and their ovarian tissues were gathered for the purposes of histopathological analysis by H&E staining, immunohistochemical assessment via proliferating cell nuclear antigen (PCNA) and follicle-stimulating hormone receptor (FSHR) immunostaining, and biochemical evaluation via measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). In addition, serum samples were collected from the blood of mice to perform hormonal analyses, especially 17β-estradiol (E2), progesterone (P4), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). ResultsThe results demonstrated that MAL exposure resulted in the development of abnormalities in the architecture and structure of ovaries. Also, the treatment of mice with MAL led to declined follicular counts at all three stages, namely, primary, secondary, and tertiary, reduced serum levels of sex hormones, decreased immunoreactivity of FSHR and PCNA, and diminished activity of CAT and SOD enzymes. In contrast, it caused an increase in MDA, IL-1β, and TNF-α, as well as the count of atretic follicles. Nonetheless, it was observed that HES exhibited the ability to ameliorate the deleterious impacts of malathion across all the aforementioned parameters. ConclusionTreatment with HES via upregulating the protein expression of PCNA and FSHR and activating antioxidant defense was able to ameliorate the adverse effects of MAL on ovarian tissues.

Silk Fibroin Encapsulated Icariin Nanoparticles Mitigate Bisphenol A-Induced Spermatogenesis Dysfunction.

Bisphenol A (BPA) is a prevalent endocrine disruptor found in natural environments. Exposure to BPA has been associated with male infertility. The natural phytochemical icariin (ICA) has demonstrated significant promise for the treatment of male infertility. However, its effectiveness is limited due to its low bioavailability, poor water solubility, and insufficient targeting abilities. Herein, novel nanoparticles are generated from the natural silk fibroin, which are used to load ICA. The efficient drug delivery system (ICA-SNPs) result in significantly focused drug distribution to spermatogonium, enhancing the anti-infertility properties of ICA, and can effectively mitigate spermatogenesis dysfunction induced by BPA, control serum sex hormone levels, and enhance testicular ultrastructure. Additionally, the ICA-SNPs restore spermatogenesis dysfunction primarily via the hormone biosynthesis, spermatogonium meiosis process, and glycerophospholipid metabolism.

Comparison of the Effect of Carob Capsule and acupuncture on Sperm Motility, in Idiopathic Male Infertility: A Randomised Controlled Trial

IntroductionInfertility is one of the growing health problems in most countries. However, current treatment methods have a high cost and low success rate. In this study, to facilitate the process of treating men with idiopathic infertility and testing an innovation, the effect of herbal medicine based on Ceratonia silique L. (carob capsule) and acupuncture on the sperm motility of men with idiopathic infertility was done. MethodsSixty-six men with idiopathic infertility and asthenospermia were randomly divided into three groups. The herbal and control groups received 2 400 mg of carob capsules and 800 mg of pentoxifylline tablets daily. The third group was treated with acupuncture. All subjects were examined before entering the study and at the end of the intervention regarding sperm components, serum levels of sex hormones, and the number of inflammatory factors. ResultsProgressive sperm motility (A+B) increased significantly in both the herbal and acupuncture groups compared to the control group (P = 0.01 and P = 0.02, respectively). Also, the follow-up of patients participating in the study within 1 year after the intervention showed no significant difference in the fertility of the spouses between groups (P = 0.68). ConclusionsDue to the high acceptance of complementary medicine, using carob capsules and acupuncture can be a low-cost and suitable alternative for treating idiopathic male infertility in patients with reduced sperm motility. However, further studies in the future with longer follow-ups can help clarify the ambiguities of effectiveness based on the type of disorder and the exact mechanism of these two treatments.

Effects of acute aerobic exercise on arterial stiffness in transgender men.

Testosterone replacement therapy (TRT) in transgender men (TM) results in side effects such as elevated triglycerides and increased arterial stiffness. Exercise may be useful to ameliorate such effects, but no studies have examined the effects of acute aerobic exercise in TM. This study aimed to investigate the effects of acute aerobic exercise on arterial stiffness in TM. Thirty-six participants were included, comprising 12TM (duration of TRT: 57.4 ± 30.3 months), 12 males and 12 females. All participants performed acute aerobic exercise on a treadmill at 50% heart rate reserve for 30min. Arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) was measured before exercise (Pre), 30min after exercise (Post30), and 60min after exercise (Post60). Serum sex hormone levels, and serum lipid profile were determined only before exercise. Serum low-density lipoprotein cholesterol (LDL-C) levels before exercise were significantly higher in TM than in males or females (males: p < 0.01; females: p < 0.05). At all points, baPWV in TM was significantly higher than in females (p < 0.05) and significantly lower than in males (p < 0.05). However, when comparing changes in baPWV over time in each group, significant decreases in Post30 and Post60 were seen in males compared to Pre (both p < 0.05), but no significant change after aerobic exercise was seen in TM or females. These results suggest that acute aerobic exercise yield different effects in TM than in males, but is unlikely to reduce arterial stiffness in TM receiving TRT.

Histomorphological and histomorphometric evaluation of the therapeutic role of sulforaphane on the hypothalamic-pituitary-ovarian axis in polycystic ovary syndrome rats via its potential anti-inflammatory and anti-oxidant activities

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. Sulforaphane (SFN) is a widely distributed isothiocyanate found in cruciferous vegetables. This study investigated the role of SFN on the hypothalamic-pituitary-ovarian axis in PCOS rats. Twenty-four female rats randomized into group A control received 2 ml of normal saline. Group B received 4 mg/kg body weight (bwt) I.P of estradiol valerate (EV) on the first day, groups C received 100 mg/kg bwt of SFN orally, and Group D received I.P 4 mg/kg bwt of EV follow by 100 mg/kg bwt of SFN orally. All administrations were done once daily for 30 days. Final body weight, estrous cycle, ovarian weight, blood glucose, serum sex hormones levels, serum lipid profile, ovarian antioxidants assay, ovarian inflammatory cytokines, and ovary and pituitary histology were assessed.The PCOS rats exhibited the characteristic features of PCOS. Disturbed ovarian cyclicity, histopathological alterations, decreased the number of healthy follicles and corpora lutea and increased degenerated and cystic follicles were detected by light microscopic studies. A significant increase in final body weight, ovarian weight, blood glucose, sex steroids hormone levels, and antioxidant assays in PCOS rats. Sulforaphane reduces the elevated level of serum sex steroids hormone, lipid profile, ovarian diameter, and cysts and restores healthy follicles in PCOS rats. SFN reduces the upraised levels of ovarian oxidant and inflammatory cytokines and increases the suppressed antioxidant enzymes.Sulforaphane thus ameliorates the disturbed hormonal levels, lipid profile, and antioxidant status in PCOS rats through its antioxidant and anti-inflammatory capacity.

LIPUS combined with TFSC alleviates premature ovarian failure by promoting autophagy and inhibiting apoptosis

Objective Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired autophagy in ovarian granulosa cells are the main pathological mechanisms of POF. The total flavonoids from semen cuscutae (TFSC) are often used in the treatment of gynecological endocrine disorders. In addition, low intensity pulsed ultrasound (LIPUS) is report as an effective method to improve ovarian function. This study aims to investigate the protective effect of POF by the combined use of TFSC and LIPUS. Methods POF rats model and granulosa cell model were successfully induced by tripterygium glycosides and cyclophosphamide, respectively. After that, model rats and cells received TFSC plus LIPUS administration. Then ovarian histomorphology, senescence, estrus cycle, and serum sex hormone levels were detected in rats. Ovarian tissue and granulosa cells autophagy and apoptosis levels were also assessed. Results Disturbed sex hormone levels, atrophied and senescent ovaries, and abnormal estrous cycle were found in POF rats. Meanwhile, cell autophagy was inhibited and cell apoptosis was activated in POF ovarian tissue and granulosa cells. However, TFSC combined with LIPUS improved these changes, and this combination treatment exhibited synergistic effects. The abnormal expression of the cell apoptosis-, autophagy-, and PI3K/AKT/mTOR signaling pathway-related proteins were also improved by combination treatment. Conclusion The study found that the combination of TFSC and LIPUS can alleviate POF by modulating cell autophagy and apoptosis. The findings may provide a viable scientific basis for POF treatment.

FRI192 Serum Steroid Biomarkers For The Differential Diagnosis Of Adrenocortical Carcinoma (ACC) And Adrenocortical Adenoma (ACA)

Abstract Disclosure: D. van Rooyen: None. R. Scheske: None. A.M. Lerario: None. W.E. Rainey: None. R.J. Auchus: None. G.D. Hammer: None. T. Else: None. Background: Adrenal tumors are very common, with the vast majority being benign adrenocortical adenomas (ACA). Adrenocortical carcinomas (ACC) represent only a very small proportion of adrenal tumors. Distinction between the common ACA and rare ACC relies on invasive and costly protocols which are often inconclusive. Research into the use of steroid biomarkers as a non-invasive alternative diagnostic tool has been the focus of various steroid metabolomics studies. In this study, we aimed to identify serum steroid biomarkers to distinguish ACA from ACC. Methods: This study population was comprised of 103 patient samples, including 45 (31 female) and 58 (40 female) respective samples from ACA (age 32-90) and ACC (age 16-77) patients presenting with disease at the time of sampling. No ACC patients studied had been treated with mitotane. Serum steroid levels (4 sulfates and 25 Δ4 steroids) were measured using liquid-chromatography tandem mass spectrometry (LCMS/MS) with comparisons made between steroid profiles in ACA vs ACC and between males and females within each group (ACA and ACC). Data were analyzed to obtain the geometric means with 95% CIs, and statistical significance was determined using a two-tailed Mann-Whitney test. Results: ACC patients were characterized by significantly elevated levels of pregnenolone-sulfate, 17hydroxypregnenolone-sulfate, 11-deoxycorticosterone, 17hydroxyprogesterone, and androstenedione when compared to ACA patients. In addition, steroid levels differed between male and female samples, with dehydroepiandrosterone-sulfate (p&amp;lt;0.01), androstenediol-3-sulfate (p&amp;lt;0.05), 11deoxycortisol (p&amp;lt;0.0001), cortisol (p&amp;lt;0.05) and testosterone (p&amp;lt;0.01) significantly increased in female ACC patients when compared to male counterparts. Conclusion: Significant differences in plasma steroids were observed in ACC vs ACA patients, with more steroids altered in female patients. Serum steroid profiles, particularly steroid sulfates, might serve as an adjunct, easy to obtain diagnostic tool to differentiate ACA and ACC. Presentation: Friday, June 16, 2023

SAT385 Pituitary Immune Cells Regulate Gonadotrope Hormone Secretion

Abstract Disclosure: Z. Del Mundo: None. T. Nguyen: None. N. Ujagar: None. D. Nicholas: None. Polycystic ovary syndrome (PCOS) is one of the most common causes of female infertility in the US and is associated with a combination of reproductive neuroendocrine physiological changes. Previous studies have shown that PCOS patients have elevated serum C reactive peptide and lipopolysaccharide (LPS), which indicates chronic low-grade inflammation. However, it is unknown how inflammation or immune cells impact reproductive outcomes. In this project, I study how inflammation affects gonadotrope regulation of sex hormone secretion. I show that in vitro depletion of immune cells from dispersed primary mouse pituitary increases the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio. In contrast, immune activation through chronic LPS exposure in mice results in decreased serum LH to FSH ratio. Using single-cell RNA sequencing data from immune cell-enriched mouse pituitaries, I identified specific resident immune cell populations. These cell populations include macrophages with higher RNA expression of heat shock proteins in male mice compared to female mice suggesting inflammatory protection in males. Ongoing experiments include chronic LPS exposure in mice, where pituitary cells are immunophenotyped, sex hormone serum levels measured, and ovulation monitored. Ultimately this work will allow us to understand the contribution of inflammation to PCOS, with the hope of designing immunotherapy for PCOS. Presentation Date: Saturday, June 17, 2023

Comprehensive evaluation of the effect of inactivated SARS-CoV-2 vaccination on female fertility: A retrospective cohort study.

Fear of possible negative effects of coronavirus disease 2019 (COVID-19) vaccine on fertility is the main reason for vaccine hesitancy among the public especially women of childbearing age. Despite the high coverage of COVID-19 vaccination in China, more scientific evidence is still needed to address their concerns and guide fertility counseling and management in the future. Herein, we performed a retrospective cohort study at a single large center for reproductive medicine in China between August 2020 and May 2023. Patients aged 20-42 years with no history of laboratory-confirmed COVID-19 were included and categorized into different groups according to their vaccination status. The serum sex hormone levels, anti-Müllerian hormone concentrations, embryo quality, and pregnancy outcomes were evaluated and compared among them. We found there were no significant differences in the concentrations of follicle-stimulating hormone, luteinizing hormone and progesterone between the unvaccinated, first-dose, second-dose, and booster vaccinated groups. However, the estradiol showed a highly significant increase in the one-dose vaccinated group compared with its levels in other groups. Among unvaccinated and either vaccinated patients, anti-Müllerian hormone levels were comparable (p = 0.139). The number of oocytes retrieved, fertilization rate and good-quality embryo rate were all similar between each group of in vitro fertilization and intracytoplasmic sperm injection. No significant differences were observed regarding other laboratory parameters. Moreover, the vaccination status of infertile couples did not exert any adverse effect on the pregnancy outcomes in all assisted reproductive technologies cycles. In short, we comprehensively evaluated the reproductive safety of inactivated severe acute respiratory syndrome coronavirus 2 vaccine and found any dose of vaccination wouldn't negatively affect female fertility parameters such as sex hormone levels and ovarian reserve. Moreover, this is the first study to complete the live birth follow-up of the cohort after receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccine, further dispelling the misconception and providing reassurance for decision-making by clinicians.

In vivo study of orange peel fermentation and improvement of androgen overproduction causing acne

Acne is a chronic disease caused by inflammation of the sebaceous glands of the hair follicles, which can leave scars on the face or body surface and cause great physical and psychological problems. This study aimed to optimize the orange peel fermentation process and also to evaluate the effect of fermentation on the effect of orange peel ethanol extracts on the improvement of acne. The results showed that under the fermentation of Aspergillus oryzae var.effuses AS3.2825, the highest flavonoid and total phenolic contents were found in the ethanolic extract of orange peel, reaching a peak of 7.52 mg/g at 96 h. The HPLC results showed that the flavonoids in the ethanol extracts of orange peel before and after fermentation were mainly hesperidin, narirutin, nobiletin, and sinensetin, with hesperidin content being the highest before and after fermentation at 0.239 mg/g and 1.115 mg/g respectively. Finally, compared with the model group, each group could significantly adjust the serum sex hormone level, and significantly reduce the inflammatory factor and TG level, among which the effect of HAG was the most obvious. Therefore, the HAG had the best effect on acne improvement.

Effects of electroacupuncture on the secretion function of ovarian cells and kisspeptin/kiss1r system in rats with polycystic ovarian syndrome

To observe the effects of electroacupuncture （EA） on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome （PCOS）, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats. Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole （0.1 mg/mL, 10 mL•kg-1•d-1）. In the EA group, EA （2 Hz, 2 mA） was used to stimulate "Guanyuan" （CV4） for 20 min each time. In the flutamide group, flutamide solution （50 mg•kg-1•d-1） was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone （T）, luteinizing hormone （LH） and estradiol （E2） in serum, the contents of E2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot. Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was decreased （P<0.01） in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was increased （P<0.05, P<0.01）. EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.

Effects of electroacupuncture on the secretion function of ovarian cells and kisspeptin/kiss1r system in rats with polycystic ovarian syndrome

To observe the effects of electroacupuncture （EA） on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome （PCOS）, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats. Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole （0.1 mg/mL, 10 mL•kg-1•d-1）. In the EA group, EA （2 Hz, 2 mA） was used to stimulate "Guanyuan" （CV4） for 20 min each time. In the flutamide group, flutamide solution （50 mg•kg-1•d-1） was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone （T）, luteinizing hormone （LH） and estradiol （E2） in serum, the contents of E2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot. Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was decreased （P<0.01） in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased （P<0.01, P<0.05）； and the content of E2 in the culture medium of granulosa cells was increased （P<0.05, P<0.01）. EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.

The potential protective effect of melatonin and N-acetylcysteine alone and in combination on opioid-induced testicular dysfunction and degeneration in rat

Methadone (Met) is the most common treatment for opioid addiction. Although Met is effective for treatment of opioid dependence, sexual dysfunctions and infertility have been reported as a major problem in patients under Met treatment. The present study aimed to evaluate the effect of melatonin and N-acetylcysteine (N) on morphine and Met-induced oxidative stress, apoptosis, suppression of blood sexual hormones, impairment in sperm parameters, and sexual dysfunction. Adult male Wistar rats (n = 66) were randomly divided into 11 equal groups (n = 6) as follows: control, sham, morphine, Met, Met+N, Met+ melatonin, Met+melatonin+N, morphine+ Met, morphine+Met+ melatonin, morphine+Met+N, and morphine+Met+ melatonin+N groups. On day 56 post-treatment, the blood was collected from the tail and the serum levels of sex hormones were evaluated, then the rats were sacrificed, and their bilateral testes and epididymis were retrieved for histological, immunohistochemical, molecular, testicular tissue stress oxidative status, and sperm parameters assays. Exposure to morphine, Met, and shift of morphine to Met resulted in testicular degeneration that can be attributed to generating the stress oxidative-induced- apoptotic testicular cell death and impairing spermatogenesis. Melatonin and N alone and particularly, in combination with each other improved testicular degeneration, sex hormone suppression, and testicular function mediated by increasing the testicular antioxidant capacity and inhibition of the apoptosis pathway. It’s suggested that oral administration of antioxidants may be an effective treatment for attenuating some opioid-related testicular dysfunction and degeneration.

Traditional Chinese Medicine formula Wubi Shanyao Pills protects against reproductive aging by activating SIRT1/3 to reduce apoptosis

Ethnopharmacological relevanceThe study of male reproductive aging and its associated concerns holds significant importance within the realm of health issues affecting the elderly population. Wubi Shanyao Pills (WSP), a traditional Chinese patent medicine originating from the Tang Dynasty, has been recognized for its ability to enhance male sexual functions while also tonifying the kidney and spleen. Nevertheless, the precise effects and underlying mechanisms through which WSP ameliorates the decline in reproductive function among aging men remain uncertain. Aim of the studyThis study elucidated the distinctive impacts of WSP on ameliorating the decline in reproductive function caused by natural aging, as well as its underlying mechanisms. Materials and methodsInitially, male mice at the age of 15 months were administered WSP orally at doses of 0.375, 0.75, and 1.50 g/kg per day for a duration of 8 consecutive weeks. The impact of WSP on age-related manifestations in naturally aging mice was assessed based on their behavioral performance. The renal function of the mice was evaluated by measuring serum biochemical indicators, including Creatinine (CR), Uric acid (UA), and Blood urea nitrogen (BUN). Additionally, Superoxide dismutase (SOD) and Malonaldehyde (MDA) levels in renal tissue were determined using applied chemistry methods. Then assessed the levels of Nitric oxide (NO), Total nitric oxide synthase (T-NOS), Guanosine cyclase (GC), and Cyclic guanosine monophosphate (cGMP) in the penile tissue, as well as the expression of Endothelial nitric oxide synthase (eNOS) and Guanylate Cyclase Activator (GUCA) protein, in order to investigate the erectile function of the penis. Additionally, the quality of epididymal sperm was examined using an electron microscope. Furthermore, the serum sex hormone level and related protein expression were determined through the utilization of enzyme-linked immunosorbent assay and immunohistochemistry techniques. Pathological alterations and the ultrastructure of the testis were investigated using hematoxylin-eosin staining and transmission electron microscopy. Subsequently, the apoptosis of spermatogenic cells in the testes was assessed employing TUNEL, immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction. ResultsThe administration of WSP has been found to enhance the behavioral performance and sexual behavior in aged mice. It's also could increase in serum levels of CR, UA, and BUN, as well as the elevation of SOD activity in kidney tissue, which subsequently leads to a reduction in MDA levels and an improvement in the structural damage caused by aging in the kidney tissue. Consequently, the renal function is enhanced. Additionally, WSP has been observed to elevate the levels of NO, T-NOS, GC, and cGMP in penile tissue, along with an increase in eNOS and GUCA protein expression, indicating an improvement in penile erectile function. The administration of WSP resulted in a decrease in the occurrence of programmed cell death in testicular germ cells, leading to an enhancement in sperm quality and the overall function of testicular spermatogenesis. This improvement can be attributed to the modulation of hormone levels and the regulation of SIRT1/3, p53, FOXO3, Bax, and Caspase-3 expression. ConclusionCollectively, our findings indicate that the administration of WSP has the potential to impede the occurrence of programmed cell death in testicular cells by modulating the expression of SIRT1/3 and subsequent genes associated with apoptosis. Consequently, this regulatory mechanism facilitates the proliferation of testicular cells and sustains the spermatogenic function of the testes. Consequently, by modulating the levels of sexual hormones in naturally aging mice, WSP ultimately enhances the quality of sperm and reproductive function. Concurrently, it also ameliorates age-related behavioral changes, renal function, and erectile function.

Vitamin E Ameliorates Impaired Ovarian Development, Oxidative Stress, and Disrupted Lipid Metabolism in Oreochromis niloticus Fed with a Diet Containing Olive Oil Instead of Fish Oil.

Aquaculture feed containing olive oil (OO) instead of fish oil (FO) can cause oxidative stress and impair gonad development in fish. We determined the effect of dietary OO-induced oxidative stress on ovarian development, and explored whether vitamin E (VE) could mitigate negative effects. Female Nile tilapia (Oreochromis niloticus) were fed for 10 weeks with four diets: 5% OO + 70 mg/kg VE, 5% OO + 200 mg/kg VE, 5% FO + 70 mg/kg VE, or 5% FO + 200 mg/kg VE. Dietary OO reduced the specific growth rate and gonadosomatic index, inhibited superoxide dismutase and catalase, delayed ovarian development, decreased serum sex hormone levels, and reduced ovarian triglyceride and n-3 highly unsaturated fatty acid contents. The transcript levels of genes encoding sex hormone receptors (erα, fshr, lhr) and components of the lipid metabolism pathway (pparα, pparγ, hsl, accα, elovl6), the nrf2 signaling pathway (nrf2, keap1), and the nf-κb signaling pathway (nf-κb, tnfα, infγ, il1β) differed between the 70VE/OO and 70VE/FO groups. Supplementation with 200 mg/kg VE mitigated the adverse effects of OO by improving antioxidant capacity and alleviating inflammation and abnormal lipid metabolism. This may be because VE is an antioxidant and it can regulate the nrf2-nf-κb signaling pathway.

Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency.

Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways.