Serum E2 Levels Research Articles

New insights into the role of myostatin in fish fertility based on the findings in mstnb-deficient Nile tilapia (Oreochromis niloticus)

Myostatin (Mstn) was reported to be involved in multiple biological processes including the regulation of skeletal muscle growth, lipid metabolism and reproduction in vertebrates, therefore, it might play an essential role in the fine balance between growth and reproduction. In order to clarify the roles of Mstn in fish reproduction, we systematically investigated the gonadal development and fertility of mstnb mutants in Nile tilapia (Orochromis niloticus). In the present study, mstnb was found to be expressed in the different cell types of gonads by fluorescence in situ hybridization (FISH). Mutation of mstnb resulted in excessive proliferation of phase II follicles in the ovaries while the numbers of phase III follicles were significantly reduced at 210 days after hatching (dah). Interestingly, significant decline of cyp19a1a gene expression, the serum 17β-estradiol (E2), vitellogenin (VTG) were detected at 210 dah. At 360 dah, the ovarian development of mstnb-/- XX tilapia was partially recovered and female fish spawn regularly, however, they were subfertile and produced the poor-quality eggs with significantly lower offspring survival rate. The dramatic up-regulation of cyp19a1a gene expression and serum E2 level at 360 dah might account for the recovery of ovarian development. In mstnb-/- males, excessive proliferation of spermatogonia and retardation of testicular differentiation were found throughout the whole development stages. In mstnb-/- males, evident declines of gonadosomatic index (GSI), cyp11b2 gene expression, and 11-Ketotestosterone (11-KT) were detected at 210 dah, while the mRNA level of cyp11b2 and serum 11-KT level were significantly upregulated at 360 dah. However, mstnb-/- males were infertile since mutation of mstnb gene led to excessive increase of apoptosis of testicular cells and spermiation obstacle. Taken together, these results indicated that Mstn might be an essential regulator for the maintenance of fish fertility.

Danggui Shaoyao San protects cyclophosphamide-induced premature ovarian failure by inhibiting apoptosis and oxidative stress through the regulation of the SIRT1/p53 signaling pathway

Ethnopharmacological relevanceIt has been reported that apoptosis and oxidative stress are related to cyclophosphamide (CYC)-induced premature ovarian failure (POF). Therefore, anti-apoptotic and anti-oxidative stress treatments exhibit therapeutic efficacy in CYC-induced POF. Danggui Shaoyao San (DSS), which has been extensively used to treat gynecologic diseases, is found to inhibit apoptosis and reduce oxidative stress. However, the roles of DSS in regulating apoptosis and oxidative stress during CYC-induced POF, and its associated mechanisms are still unknown. Aim of the studyThis work aimed to investigate the roles and mechanisms of DSS in inhibiting apoptosis and oxidative stress in CYC-induced POF. Materials and methodsCYC (75 mg/kg) was intraperitoneally injected in mice to construct the POF mouse model for in vivo study. Thereafter, alterations of body weight, ovary morphology and estrous cycle were monitored to assess the ovarian protective properties of DSS. Serum LH and E2 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was employed for examining ovarian pathological morphology and quantifying follicles in various stages. Meanwhile, TUNEL staining and apoptosis-related proteins were adopted for evaluating apoptosis. Oxidative stress was measured by the levels of ROS, MDA, and 4-HNE. Western blot (WB) assay was performed to detect proteins related to the SIRT1/p53 pathway. KGN cells were used for in vitro experiment. TBHP stimulation was carried out for establishing the oxidative stress-induced apoptosis cell model. Furthermore, MTT assay was employed for evaluating the protection of DSS from TBHP-induced oxidative stress. The anti-apoptotic ability of DSS was evaluated by hoechst/PI staining, JC-1 staining, and apoptosis-related proteins. Additionally, the anti-oxidative stress ability of DSS was measured by detecting the levels of ROS, MDA, and 4-HNE. Proteins related to SIRT1/p53 signaling pathway were also measured using WB and immunofluorescence (IF) staining. Besides, SIRT1 expression was suppressed by EX527 to further investigate the role of SIRT1 in the effects of DSS against apoptosis and oxidative stress. ResultsIn the in vivo experiment, DSS dose-dependently exerted its anti-apoptotic, anti-oxidative stress, and ovarian protective effects. In addition, apoptosis, apoptosis-related protein and oxidative stress levels were inhibited by DSS treatment. DSS treatment up-regulated SIRT1 and down-regulated p53 expression. From in vitro experiment, it was found that DSS treatment protected KGN cells from TBHP-induced oxidative stress injury. Besides, DSS administration suppressed the apoptosis ratio, apoptosis-related protein levels, mitochondrial membrane potential damage, and oxidative stress. SIRT1 suppression by EX527 abolished the anti-apoptotic, anti-oxidative stress, and ovarian protective effects, as discovered from in vivo and in vitro experiments. ConclusionsDSS exerts the anti-apoptotic, anti-oxidative stress, and ovarian protective effects in POF mice, and suppresses the apoptosis and oxidative stress of KGN cells through activating SIRT1 and suppressing p53 pathway.

Comparison of endogenous hypothalamic and serum OT levels between young and middle-aged perimenopausal female rats.

Oxytocin (OT) regulates food intake and body weight, particularly in obese individuals. Decreases in the effects of OT have recently been implicated in metabolic disturbances, and the administration of estradiol (E2) increased serum OT levels. Although weight gain is frequently observed in perimenopausal women, endogenous OT levels remain unclear. Therefore, we herein compared endogenous levels of hypothalamic and serum OT between young and middle-aged perimenopausal female rats and examined the relationship between serum estrogen and leptin levels. Body weight and visceral and subcutaneous fat weights were higher in middle-aged rats. Although no significant differences were observed in serum OT and E2 levels, serum leptin levels and hypothalamic mRNA levels of OT and the OT receptor (OTR) were significantly higher in middle-aged rats than in young rats. Serum OT levels did not correlate with hypothalamic OT mRNA levels or serum E2 levels. E2 maintains serum OT levels in perimenopausal rats, and other factors may elevate hypothalamic OT/OTR mRNA levels. Increases in body and fat weights in perimenopausal rats may be attributed to factors other than OT. Therefore, the administration of OT alone may not be sufficient to prevent metabolic disorders induced by the perimenopausal status. J. Med. Invest. 71 : 246-250, August, 2024.

The effect of serum estrogen level on male infertility & semen parameters on Sudanese males attending Khartoum Dermatology Teaching Hospital

Background Infertility is defined as the inability to achieve pregnancy after one year of unprotected intercourse. As estimated 10–15% of couples were considered infertile by W.H.O. One of the major causes of non-obstructive infertility is hormonal disturbance. Testosterone and Estrogen, traditionally, have been regarded as male and female sex hormones respectively. However, Estradiol, the predominant form of Estrogen, also plays a pivotal role in male sexual function. Estradiol in men is quintessential in many sexual physiological processes. Objectives To evaluate the effect of Estrogen levels on infertile men and their semen parameters Method In this prospective case-control hospital based study, a total number of 50 infertile men with primary and secondary infertility (case group) and 50 fertile men (control group) were included. The medical histories of all the participants were taken and physical examinations were conducted thoroughly. Serum Estradiol (E2) levels were measured for both infertile and fertile group. Seminal analysis was done for the infertile group. Serum E2 was measured by Radio-Immunosorbent Assay (RIA) using Estradiol kits for measurement. Standard semen analysis was done by computer-assisted seminal analysis (CASA) using the WHO manual 2010. The collected data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25. The results were obtained and presented in tables and diagrams. The significance of testing was assessed by Chi-Square T test with P value ≤0.05 was considered statistically significant. Results A significant correlation was observed between the fertility status and serum E2 levels. 18% (n=9) of the subfertile patients were found to have serum E2 levels more than 55 pg/ml. on the other hand, only 6% (n=3) of the fertile group (control group) were above 55 pg/ml (P value less than 0.05). Azoospermia was found to be the most semen parameter among patients with elevated serum E2 level (P value less than 0.05). It is also observed that 46% of the infertile patients were found to be overweight (BMI=25–29.9) & they have significantly high serum E2 levels (P value less than 0.05). Conclusion High serum Estradiol levels were found significantly correlated with male infertility; Azoospermia was the most commonly observed abnormal semen parameter. Overweight patients have significantly elevated Serum E2 levels.

Evaluation of the therapeutic effect of very small stem cells from peripheral blood on the treatment of Premature Ovarian Failure: A pilot study.

Premature ovary failure (POF) is a severe health condition with multiple negative outcomes, which deteriorate a patient's life. The current study aimed to evaluate the therapeutic effect of mesenchymal stem cells (MSCs) derived from peripheral blood in the treatment of women with the POF background. The current study was a pilot study carried-out on women younger than 40 with premature ovarian failure. Study participants underwent 4-months cell therapy using Mesenchymal stem cells extracted from peripheral bloods. Serum level of Follicle-stimulating hormone (FSH), Estradiol (E2), Anti-mullerian hormone (AMH), and Antral follicle count (AFC) were the main investigated outcomes that were assessed at baseline, month two and month four of the very small stem cell intervention. Average serum level of FSH was 45.0 (12.1) mIU/mL at baseline and continually decreased during the study and reached 33.2 (12.4) mIU/mL in the fourth month. The average AMH level was 0.10 ng/mL prior to the intervention and increased to 0.13 ng/mL in the 2nd month and 0.15 ng/mL in the fourth month. The level E2 was 85.7 (23.6) pg/ml on average at baseline, while the average E2 reduced to 77.2 (25.6) pg/ml in the fourth month. Average number of AFC was 2.0 (0.8) at baseline. We observed a gradual increase in the second month (Mean AFC=2.2) and after four months it increased to 3.1 (1.8) as the highest menstrual restoration and pregnancy was observed in 10% of our study participants. MSCs could significantly improve hormone secretion in women with POF. Implantation of MSCs in women with POF background was associated with an increase in AMH and AFC, while it downed the serum level of E2 and FSH. MSCs could also lead to menstrual restoration and pregnancy in women with POF.

Sequence identification and expression characterization of leptin in the spotted scat, Scatophagus argus.

Scatophagus argus is an important marine culture fish in South and South-East Asia, including Southeast coastal areas of China. Artificial propagation technology for S. argus is not optimum; thus further studies on its reproduction biology are required. Although previous studies have shown that leptin (Lep) can regulate fish reproduction, the role of lep genes in S. argus is unknown. Herein, in silico analysis showed that S. argus has two lep genes (lepa and lepb). Protein 3D-structure prediction showed that Lepa has four α-helices (similar to mammals), while Lepb only has three. Tissue distribution analysis showed that lepa is highly expressed in the liver, whereas lepb was not detected in any tissue. Notably, lepr was expressed in all tissues. Lepa mRNA expression levels in the liver and serum Lep, estradiol (E2) and vitellogenin (Vtg) levels of female fish were significantly higher in ovaries at stage IV than in ovaries at stage II. Serum E2 levels were significantly positively correlated with Vtg levels in female fish at different development stages, while serum E2 was not correlated with Lep levels. Consistently, in vitro incubation of the liver with E2 significantly up-regulated vtga, while it did not affect lepa expression. Recombinant Lep (10nM) significantly up-regulated chicken gonadotropin-releasing hormone (cGnRH/GnRH-II) in the hypothalamus and GnRH receptor (GnRHR) and luteinizing hormone beta (Lhb) in the pituitary. These results suggest that lepa regulates female reproduction in S. argus.

Effects of a simple method for determining the time of insemination and different methods on artificial insemination in common bottlenose dolphins (Tursiops truncatus).

In this study, we examined the usefulness of a simpler and more feasible method for determining the optimal timing of artificial insemination and the conditions for its success in six female common bottlenose dolphins. Pregnancy was successfully achieved in five dolphins by performing intrauterine insemination, using chilled semen stored for less than 3 days or frozen semen within 24 hr of exhibiting a peak serum estradiol (E2) level of 100 pg/mL or higher or on the day with a serum E2 level of approximately 100 pg/mL, measured with a simple measuring device. We concluded that the determining the optimal timing of intrauterine insemination by measuring serum E2 levels is a simpler and more useful method compared with the conventional approach.

Варианты патогенетического лечения аспирининдуцированных гастроэнтеропатий у лиц с хронической ишемической болезнью сердца

Aim: Evaluation of Rebamipide treatment efficiency for aspirin-induced gastroduodenopathy in the patients with stable coronary heart disease (CHD). Design: Randomised controlled study. Materials and methods: In the course of the conducted research 340 CHD patients receiving long-term acetylsalicylic acid therapy in cardioprotective doses were studied. All the patients received complete clinical laboratory examination. For CHD verification there was applied selective method of coronary angiography. Gastroduodenopathy was verified by esophagogastroduodenoscopy. In both cases frequency and structure of the aforesaid events were assessed. For aspirin-induced gastroduodenopathy treatment there were applied either endogenic prostaglandin stimulant Rebamipide in combination with proton pump inhibitor (PPI) Pantoprazole (study group, n = 26) or Pantoprazole only (control group, n = 25). Prior to initiating therapy and on completion all the patients were taken blood samples for evaluation of prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukine-1β Il-1β and interleukine-6 Il-6, TNF-α) levels in blood serum for verification of pathogenetic mechanisms in erosive or ulcer-bearing areas developing in gastrointestinal mucosa in association with long-term aspirin therapy. Соntrol group consisted of 26 CHD patients with no evidence of gastroduodenopathy. Statistical processing of the received data was conducted with the software program “Statistics 10.0”. Results. Aspirin-induced gastroduodenopathy was identified in 51 out of 340 (15,0%) cases. According to esophagogastroduodenoscopy data, erosions of the body and antrum of stomach were prevailing (43,1%) over all the erosive damages. CHD patients before the gastroduodenopathy treatment had significantly lower PGE2 levels in comparison with control group (p < 0,01), while proinflammatory cytokines indices were higher (p < 0,001). On the treatment completion 19 patients in the control group did not show endoscopic evidence of gastroduodenopathy, the laboratory findings tended to normalization. Gastric mucosa condition in the study group stabilized in all the cases, which was confirmed by statistically significant PGE2 level positive alterations (p < 0,001) and also cytokine profile alterations (TNF-α: p < 0,001; Il-1β and Il-6: p < 0,01). Conclusion. The presented study demonstrates clinical features of aspirin-induced gastroduodenopathy development in the CHD patients and proposes possible ways of correction. Key words: aspirin-induced gastroduodenopathy, acetylsalicylic acid, prostaglandin E2, proinflammatory cytokines, rebamipide.

Estradiol Decline Before hCG Administration in COH Has a Negative Effect on IVF Outcomes in Patients Without OC Pretreatment.

Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019. In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups. Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes. E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.

Clinical observation of kidney-tonifying and mind-calming acupuncture therapy in the treatment of perimenopausal insomnia

Abstract Objective To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep, mood, sex hormone levels, and traditional Chinese medicine (TCM) symptoms in patients with perimenopausal insomnia (PMI). Methods A total of 90 patients with PMI were randomly divided into a treatment group and a control group, with 45 cases in each group. Patients in the treatment group were treated with acupuncture at Shenshu (BL23), Taixi (KI3), Baihui (GV20), and Anmian (Extra). The control group was treated with sham acupuncture. Both groups were treated 3 times a week for 4 weeks. Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were used to evaluate the sleep quality of the subjects before treatment, after treatment, and 1 month after treatment (follow-up). Beck depression inventory (BDI) and Beck anxiety inventory (BAI) were used to evaluate the depression and anxiety of the subjects before treatment, after treatment, and at 1-month follow-up. The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment, after treatment, and 1 month after treatment. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured before and after treatment. Results During the study, 2 cases dropped out of the treatment group, and no cases dropped out of the control group. The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment (P<0.05), and the difference was statistically significant compared with that of the control group (P<0.05). In the control group, the PSQI score was significantly lower after treatment compared with before treatment (P<0.05), and the difference was not statistically significant at 1-month follow-up compared with before treatment (P>0.05). Compared with the pre-treatment, the ISI, BDI, BAI, and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up (P<0.05), and the differences with the control group at the same time point were statistically significant (P<0.05). The differences in ISI, BDI, BAI, and TCM symptom scale scores of the control group before treatment, after treatment, and at 1-month follow-up were not statistically significant (P>0.05). After treatment, the serum E2 level in the treatment group was significantly higher than that before treatment (P<0.05), and the difference with the control group was statistically significant (P<0.05). The difference in the serum E2 level before and after treatment in the control group was not statistically significant (P>0.05). The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects (P>0.05). Conclusion Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality, relieve anxiety and depression, delay the decrease of serum E2 level, and improve related TCM symptoms in patients with PMI.

Plasma cytokines profile in patients with Alzheimer’s and Parkinson’s Disease: a comparative study in terms of inflammation

Background Neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease inflict economic and health burdens on societies. Alzheimer’s disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson’s disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. Methods To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. Results Our results showed a significant increase in IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. Conclusion As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Effects of acupuncture on RT-BM1 and maternal-fetal immune tolerance in rats with ovarian hyperstimulation: 针刺对超排卵大鼠RT-BM1及母胎免疫耐受的影响

ObjectiveThis study aimed to evaluate the effects of acupuncture on embryo implantation and maternal–fetal immune tolerance in rats with ovarian hyperstimulation, identify the mechanisms of acupuncture treatment, and promote application of acupuncture in the field of assisted reproduction. MethodsEighty female Wistar rats were randomized into normal (N), model (M), acupuncture treatment (A), and progesterone treatment (P) groups, with 20 rats in each group. An ovarian hyperstimulation model was established in groups M, A, and P by the peritoneal injection of pregnant mare serum gonadotropin (PMSG) combined with human chorionic gonadotropin (HCG). Bilateral “Sanyinjiao (SP6)”, “Zusanli (ST36)” and “Taichong (LR3)” as acupoints were needled in rats in group A. Rats in group P received an intramuscular injection of progesterone (4 mg/kg). All pregnant rats were treated for seven days. On the 8th day, the pregnant rats were sacrificed for testing. The expression levels of estrogen (E2) and progesterone (P4) in serum and their receptors in the endometrium, Th1 and Th2 cytokines in serum and endometrium, RT-BM1 (the counterpart of HLA-G in rats) mRNA, Ly49 activating receptors (Ly49s3, Ly49s5) and inhibitory receptors (Ly49i3, Ly49i4, Ly49i5) on immunocytes in the maternal–fetal interface were detected using ELISA, Western blot, and real-time polymerase chain reaction (PCR). ResultsCompared with group N, the pregnancy rate and the number of implanted embryos were significantly decreased in group M (P < 0.05); E2 and P4 levels in serum, and the protein levels of ER-α and Progesterone Receptor (PGR) in the implantation site of endometrial tissue were significantly reduced in group M (P < 0.05); the expression of INF-γ and IL-2 in serum and endometrium were significantly increased, while the expression of IL-4, IL-6, and IL-10 in serum and endometrium were significantly decreased in group M(P < 0.05). The mRNA levels of RT-BM1, Ly49i3, and Ly49i4 receptors in group M were significantly higher than those in group N, whereas the mRNA levels of Ly49i5 and Ly49s5 receptors in group M were significantly lower than those in group N at the maternal–fetal interface (P < 0.05). The pregnancy rate and number of implanted embryos were significantly higher in group A than in group M (P < 0.05). Serum E2 and P4 levels were significantly higher in groups A and P than in group M (P < 0.05). The expression of ER-α and PGR in the implantation site of endometrial tissue in group A were significantly higher than those in group M (P < 0.05). The serum levels of INF-γ and IL-2 in group A and group P were significantly lower than those in group M (P < 0.05). The serum expression of IL-4, IL-6, IL-10 in group A and group P were significantly higher than those in group M (P < 0.05). The endometrium expression of INF-γ and IL-2 in group A were significantly lower than those in group M (P < 0.05). The endometrium expression of IL-4, IL-6, IL-10 in group A were significantly higher than those in group M (P < 0.05). The endometrium expression of INF-γ in group P were significantly lower than those in group M (P < 0.05). The endometrium expression of IL-6 and IL-10 in group P were significantly higher than those in group M (P < 0.05). The mRNA levels of RT-BM1 and these Ly49 receptors (except the Ly49s3 receptor) at the maternal–fetal interface of groups A and P were higher than those of group M (P < 0.05). ConclusionAcupuncture can significantly increase the pregnancy rate and average number of implanted blastocysts in rats with ovarian hyperstimulation. This mechanism is related to the effects of acupuncture in upregulating the expression of RT-BM1, regulating the balance of Th1/Th2 cytokines, and upregulating the expression of inhibitory receptors in immunocytes.

Revealing Sexual Dimorphism in Prolactin Regulation From Early Postnatal Development to Adulthood in Murine Models.

Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to age-matched males. This pattern has traditionally been attributed to the development and maturation of endocrine and neuroendocrine networks responsible for regulating PRL synthesis and secretion. However, the effect of dopamine (DA), which acts as an inhibitory factor on lactotroph function, also increases from birth to puberty, particularly in females. Nonetheless, the secretion of PRL remains higher in females compared to males. On the other hand, the observed sex differences in serum PRL levels during early postnatal development cannot be attributed to the influence of estradiol (E2). While serum E2 levels gradually increase after birth, only after 45 days of life do the disparities in E2 levels between females and males become evident. These observations collectively suggest that neither the maturation of hypothalamic DA regulation nor the rise in E2 levels can account for the progressive and sustained elevation in serum PRL levels and the observed sexual dimorphism during postnatal development. This review highlights the importance of recent discoveries in animal models that shed light on inhibitory mechanisms in the control of PRL secretion within the pituitary gland itself, that is intrapituitary mechanisms, with a specific emphasis on the role of transforming growth factor β1 and activins in PRL secretion.

Assessment of reproductive toxicity in adult zebrafish (Danio rerio) following sublethal exposure to penthiopyrad

Penthiopyrad (PO), a succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to fish. Here, we investigated the adverse effects of PO on endocrine regulation and reproductive capacity in zebrafish during a 21-d sublethal exposure to PO concentrations ranging from 0.02 to 2.00 mg/L. Following exposure to PO (0.20 and 2.00 mg/L), female-specific effects including follicle necrosis, structural disturbance of the yolk follicle, fusion of cortical follicles appeared in ovarian tissue of adult females, which led to a significant reduction in fertility. Correspondingly, 0.20 and 2.00 mg/L PO led to a marked reduction in the GSI values of females, and 2.00 mg/L PO caused a 31% decline in the proportion of perinucleolar oocytes (PCO) in oocytes. In addition, testosterone (T) level was obviously suppressed and 17β-estradiol (E2) level was increased in females after exposure to 2.00 mg/L PO. Male zebrafish treated with 0.20 and 2.00 mg/L of PO exhibited significant interstitial enlargement, edema in the testes, and reduced diameter of seminiferous tubules, along with a thinner basement membrane. The effects of PO on males were associated with significant increase in E2 level, suggesting that PO has an estrogenic effect on male fish. Greater E2 levels in serum were further supported by increased transcription levels of genes linked to the hypothalamic-pituitary-gonad-liver (HPGL) axis. Notably, transcription levels of cyp19a, er2b, era, and cyp19b was remarkably increased, exhibiting a clear link with variations in E2 levels. Overall, the present study demonstrates that PO induces reproductive impairment in zebrafish by promoting steroidogenesis.

The Relationship Between Heavy Metals and Missed Abortion: Using Mediation of Serum Hormones.

Accumulating evidence suggests that heavy metal exposure may have adverse effects on the fetal development. Furthermore, disruption of serum hormone homeostasis can result in the adverse pregnancy outcomes. Therefore, this study aimed to investigate the potential association between heavy metals and missed abortion, with a focus on whether serum hormones mediate this relationship. The concentrations of heavy metals and hormones in serum were measured in this case-control study. Statistical models including, logistic regression model, principal component analysis (PCA), and weighted quantile sum (WQS) regression model were employed to examine the relationship between heavy metals, serum hormones, and missed abortion. Furthermore, the mediation analysis was performed to assess the role of serum hormones as potential mediators in this relationship. This study revealed significant associations between heavy metal exposure and missed abortion. Notable, the WQS index weight, which was mainly influenced by copper (Cu) and zine (Zn), is associated with missed abortion. Moreover, heavy metals including manganese (Mn), nickel (Ni), Zn, arsenic (As), Cu, cadmium (Cd), and lead (Pb) were found to be associated with serum levels of β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), and lactogen (HPL). In addition, the mediation analysis indicated that β-hCG explained a portion of the association (ranging from 18.77 to 43.51%) of between Mn, Ni, Zn, and As exposure and missed abortion. Serum P levels explained 17.93 to 51.70% of the association between Ni, Cu, and As exposure and missed abortion. Serum E2 levels played a significant mediating role, explaining a portion of the association (ranging from 22.14 to 73.60%) between Mn, Ni, Cu, As, Cd, and Pb exposure and missed abortion. Our results suggested that β-hCG, P, and E2 are one of the potential mediators in the complex relationship between heavy metals exposure and missed abortion. These results highlight the importance of considering both heavy metal exposure and serum hormone levels in understanding the etiology of missed abortion.

The effect of letrozole as an adjunct in GnRH-antagonist protocol on IVF/ICSI outcome in women with endometriosis: a randomized clinical trial

BackgroundTo evaluate the effect of adding letrozole to the antagonist ovarian stimulation protocol (COS) on in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome in endometriosis patients.MethodsThis randomized clinical trial was carried out in the department of infertility treatment at Arash Women’s Hospital from May 2019 to May 2021. The eligible women with normal ovarian reserve tests who had endometriosis diagnosis and underwent IVF/ICSI cycles were evaluated. A flexible regimen of GnRH-antagonist protocol was used for COS. In the experimental (n = 34), the patients received 5 mg letrozole daily for the first 5 days in combination with 150 IU of recombinant follicle-stimulating hormone (rFSH). In the control group (n = 30), the patients received only the same dose of rFSH. The treatment cycle was compared between groups.ResultsAnalysis of demographic characteristics, severity of endometriosis, and baseline hormonal tests of patients showed that the two groups were similar and comparable. The means of total used gonadotropins ampoules and serum E2 level on oocyte trigger day in the letrozole group were significantly lower than those of in the control group (P = 0.03 and P = 0.004, respectively). No statistically significant difference in terms of the total number of retrieved and MII oocytes as well as the total numbers of obtained and top-quality embryos, and cryopreserved embryos was found.ConclusionThe co-treatment of letrozole with gonadotropins during the antagonist protocol was associated with a reduction in the total dose of gonadotropins, although it had no effect on the oocyte or embryo yield in patients with endometriosis.Trial registrationThe study was registered in the Iranian Registry of Clinical Trials on 2018 -07-13 (IRCT20150310021420N4 at www.irct.ir, registered while recruiting).

Establishment and application of high throughput screening cell model for nutrient regulation of embryonic development

Embryo development exerts far-reaching influence on pregnancy outcome, postnatal development and lifelong health. Thereafter, to select functional nutrients to improve embryo development is of great importance. Herein, a stable porcine trophectoderm cell line expressing a luciferase reporter gene driven by a 1,009 bp PCNA gene promoter was constructed through lentiviral transduction and G418 selection. A high throughput screening assay was subsequently developed using the stable reporter cell line to screen a library of 225 nutrients. Seven nutrients with a minimum Z-score of 2.0 were initially identified to be capable of enhancing embryonic development. Among these nutrients, resveratrol, apigenin, and retinol palmitate were furtherly confirmed the beneficial effects for embryo development. Resveratrol significantly increased the expression of key genes involved in pTr cell proliferation and the number of S-phase cells. Resveratrol was furtherly confirmed to promote the expression of key genes in trophoblast development and increase embryo adhesion rate in vitro. Similarly, dietary 0.05% resveratrol supplementation significantly increased the number of embryo attachment and serum level of P4 and E2 in rats. Resveratrol could also improve maternal antioxidant levels and reduce intracellular ROS. Collectively, a high throughput screening cell model for nutrient regulation of embryonic development was established, which can be used to highly effectively select the potential candidates for embryo development. These findings have great implications for exploring optimal functional nutrients to improve embryo development, ultimately beneficial for pregnancy outcome, offspring postnatal development and lifelong health for human beings and mammalian animals.

Comparison of testosterone, FSH, LH and E2 hormone levels in infertility suspected males with COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is an infectious disease that has many adverse impacts on many systems including reproduction. The direct effects of COVID-19 on urogenital system are still open to argue. This study aimed to compare testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) hormone levels in COVID-19 infected male individuals with infertility suspicion. One hundred five control (healthy) and 105 COVID-19 infected males aged between 20 to 54 years old were enrolled in the study. All patients were either diagnosed with primary or secondary infertility suspicion. The COVID-19 infection was diagnosed via reverse-transcription polymerase chain reaction test. Blood samples from patients were analyzed from the control and COVID-19 group to measure serum testosterone, FSH, LH, and E2 levels. Hormone levels were statistically compared between groups with the Independent T test. In control and COVID-19 patients, no significance was determined for FSH and LH hormone values. Testosterone hormone were significantly decreased and E2 level was statistically increased in COVID-19 patients compared to that in the control group (P < .001). COVID-19 is a viral disease that affects organ including gonads. COVID-19 infection decreased testosterone levels and increased E2 levels, which leading to disorders in male and female reproductivity.

Dietary Chinese herbal mixture supplementation improves production performance by regulating reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders

Chinese herbs have been used as feed additives and are commonly utilized in domestic intensive livestock farming. However, their impact on the production performance and intestinal health of broiler breeders has yet to be thoroughly explored. This study aimed to evaluate the effects of a Chinese herbal mixture (CHM) on the production performance of broiler breeders in terms of reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders. A total of 336 thirty-wk-old hens were randomly allotted to 4 groups with 6 replicates of fourteen hens each, which fed a basal diet supplemented with 0 (CON), 500 (CHM500), 1,000 (CHM1000), and 1,500 (CHM1500) mg/kg CHM for 56 days, respectively. Our results showed that dietary supplementation with CHM1000 increased the laying rate and number of SYF and decreased the feed conversion ratio (P < 0.05). All CHM groups increased oviduct and ovarian indexes, serum E2 and T-AOC levels, and decreased serum TG and MDA levels compared with CON (P < 0.05). In comparison to the CON group, the CHM1000 and CHM1500 groups increased serum ALB, IgM, and IL-10 levels, whereas the CHM1000 group also increased serum TP and SOD levels, and the CHM1500 group increased serum P and decreased serum TNF-α (P < 0.05). The addition of CHM increased FSHR expressions in the ovary, Claudin-1 expressions in the jejunum, and SOD1 expressions in the liver and ovary, but decreased the mRNA expressions of INH in the ovary as well as IL-2 and IL-6 expressions in the jejunum (P < 0.05). Moreover, CHM500 and CHM1000 groups increased CAT, GPx, and HO-1 expression in the ovary, and SOD1 and GPx expression in the jejunum, while decreasing IL-17A expression in the jejunum (P < 0.05). In addition, CHM1000 and CHM1500 groups increased villus height, VCR, and the mRNA expressions of Nrf2, HO-1, Occludin, and MUC2 in the jejunum, and IL-10 expression in the ovary, while decreasing IL-2 and IL-17A expression in the ovary, in addition to increasing GPx, Nrf2, HO-1, NQO1, and IL-10 expression in the liver (P < 0.05). Supplementation with CHM1000 increased ESR-α, ESR-β, GnRH, Nrf2, and NQO1 expression in the ovary, but decreased IFN-γ expression in the ovary as well as crypt depth in the jejunum (P < 0.05). Supplementing CHM1500 increased NQO1 and ZO-1 expression in the jejunum and decreased IL-2 in the liver (P < 0.05). The high-throughput sequencing results showed that dietary CHM1000 supplementation altered the composition of the intestinal microbiota, as evidenced by the regulation of the genera Lactobacillus, Faecalibacterium, and Phascolarctobacterium. PICRUSt analysis revealed that metabolic pathways of bacterial chemotaxis, butanoate metabolism, and synthesis and degradation of ketone bodies were enriched in the CHM1000 group. Spearman's correlation analysis indicated that the differentiated genera were significantly associated with the production performance, serum hormone, and gut barrier-related genes. Taken together, supplementation of CHM, especially at 1,000 mg/kg, could improve production performance by regulating reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders, and maybe provide insights into its application as a potential feed additive to promote the performance of broiler breeders.

Pinostrobin, a dietary bioflavonoid exerts antioxidant, anti-inflammatory, and anti-apoptotic protective effects against methotrexate-induced ovarian toxicity in rats

This study investigated the protective activities of pinostrobin (PIN) against methotrexate (MTX)-induced ovarian toxicity. Female rats were administered with PIN (50 mg/kg) for 4 weeks, while MTX was administered from weeks 2–4 of PIN treatment. Serum hormonal profiles, ovarian oxidative stress, inflammatory and apoptotic biomarkers as well as ovarian histomorphometry were evaluated. MTX administration elicited profound deficit in serum progesterone and estrogen (E2) levels, while luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly increased. Additionally, MTX administration was associated with significant increases in ovarian malondialdehyde, nitric oxide, NF-кB, TNF-α, IL-6, IL-1β, iNOS and caspase-3 activity, as well as notable reduction in the activities of glutathione peroxidase, catalase and superoxide dismutase as well as the level of glutathione. Whereas, treatment with PIN significantly decreased serum levels of FSH and LH, as well as ovarian levels of NO, MDA, caspase 3, NF-κB, IL-1β, IL-6, TNF-α and iNOS. PIN also significantly upregulated GSH, GPx, CAT and SOD in the ovarian tissues as well as increased serum E2 and progesterone levels compared to the MTX group. Furthermore, PIN significantly restored altered ovarian histoarchitecture in the treated group. These findings suggests that PIN exerts protective effects against MTX-triggered ovarian damages.