Serum Estradiol Levels Research Articles

Effect of Orchidectomy on Hepatic Ischemia/Reperfusion Injury

Abstract Background Little attention has been paid to investigate the effect of orchidectomy on hepatic ischemia/reperfusion (I/R) injury, which is lacking. The Aim of This Study is to evaluate the possible impact of orchidectomy and/or testosterone treatment on the function and structure of liver in rat model of hepatic I/R injury and, also, to explore the possible underlying mechanism(s). Materials and Methods 65 male Wistar albino-rats were divided into 5 groups; sham- operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone- treated hepatic ischemia/reperfusion group (T+I/R) and Orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α) and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. Results Hepatic I/R was associated with significant rise of serum ALT and AST, and hepatic tissue TNF-α, NF-κB and MDA, and significant reduction of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2. Histopathological analysis showed vacuolization of the cytoplasm, dilated sinusoids, inflammatory cells infiltration, increased collagen fibers and significantly increased caspase-3. Hepatic I/R -mediated effects were aggravated following orchidectomy, however preischemic treatment with testosterone protected the liver as shown by the significant decline in ALT and AST, and hepatic tissue MDA, TNF-α and NF-κB, and significant enhancement of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2, and restoration of hepatic architecture. Conclusion Orchidectomy hypersensitizes the liver to ischemic injury, due to exaggeration of oxidative and inflammatory states and apoptosis, while testosterone treatment improved the hepatic I/R detrimental effects on liver function and morphology due to its suppressive effect on oxidative and inflammatory states and apoptosis.

P-445 High serum estradiol on the day of frozen blastocyst transfer is associated with higher early miscarriage rates in hormonal replacement therapy cycles using transdermal estrogens

Abstract Study question Do serum estradiol(E2) levels on the day of frozen blastocyst transfer(FBT) affect the live birth rate (LBR) in hormonal replacement therapy(HRT) cycles using transdermal estrogens? Summary answer E2 levels ≥ 313 pg/mL on the day of FBT are associated with increased early miscarriage rates, but no significant impact on LBR. What is known already E2 plays a crucial role in endometrial receptivity during the periconceptional period and a massive role in placentation. However, the impact of serum E2 levels measured around the time of a FBT in HRT cycles outcomes remains controversial, with some studies showing a detrimental impact of high levels, and others underlining no difference. To this date, there is no study focusing on HRT cycles with transdermal estrogens only, though it is the safest way of estrogen administration regarding thrombo-embolic complications. Study design, size, duration Observational cohort study with 2364 patients undergoing HRT-FBT cycles at a university hospital, between January 2019 and December 2022. Women were only included once during the study period. Participants/materials, setting, methods Patients undergoing single autologous FBT under HRT using transdermal estrogens and vaginal micronized progesterone. The serum E2 level was measured in the morning of the FBT, in a single laboratory. The primary outcome was the LBR, secondary outcomes included clinical pregnancy rates, early miscarriage rates(EMR), and obstetrical outcomes. Patients were divided into three groups based on the 25th and the 75th percentiles of E2 levels and compared using univariate and multivariate logistic regression models. Main results and the role of chance A total of 2364 patients were divided into 3 groups: group A < 122 pg/mL (n = 590), group B 122-312 pg/mL (n = 1184), and group C ≥ 313 pg/mL (n = 590). Mean serum E2 level on the day of FBT was 247.8 pg/mL ± 209.01 pg/ml. The LBR was 32.0% (756/2364), and the early miscarriage rate was 26.3% (280/1075) in the overall population. Multivariate logistic regression showed a negative impact of high E2 levels (≥ 313 pg/mL) on EMR: an increase in the EMR was noted between group C and referent group B (30.3% versus 24.6%, OR 1.5 95%CI (1.06-2.17)). However, no significant impact of E2 levels was noted regarding the LBR (group C vs group B, adjusted OR 0.9 95%CI (0.69-1.10)), the clinical pregnancy rates, or the obstetrical outcomes (birthweight and term of delivery Limitations, reasons for caution The main limitation of our study is linked to its observational design. Extrapolation of our results to other laboratories, or other routes and/or doses of administering estrogens also needs to be validated. Wider implications of the findings Limiting high serum E2 levels on the day of FBT in HRT cycles may improve ART outcomes. Further studies are needed to evaluate if modifications of estrogen doses may improve pregnancy chances, in an approach to individualize the management of ART patients. Trial registration number not applicable

Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 μg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17β-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

P-588 Serum Luteinizing Hormone levels before progesterone supplementation are significantly associated with live birth rate in single euploid frozen embryo transfers performed in hormonal replacement cycles

Abstract Study question Do luteinizing hormone (LH) levels measured prior to initiating progesterone supplementation influence live birth rate (LBR) in artificial frozen-thawed single euploid blastocyst transfer cycles? Summary answer Serum LH levels, measured prior to progesterone initiation in artificial frozen-thawed single euploid blastocyst transfer cycles, are significantly associated with LBR. What is known already In the absence of a dominant follicle, estrogen supplementation in artificial endometrial preparation for frozen embryo transfer (FRET) can lead to a rise in endogenous LH levels, as observed in a natural cycle. Since the LH rise is a key feature in natural conception and the embryo, the endometrium, and the myometrium display receptors for LH, the rise observed during FRET preparation may have an impact on the clinical outcomes of the treatment. Previous studies found contradictory results hence none of them excluded embryo aneuploidy by implementation of preimplantation genetic testing for aneuploidies and the transfer of euploid embryos. Study design, size, duration Retrospective analysis of 639 frozen-thawed single euploid blastocyst transfer cycles performed in a tertiary referral IVF center from January 2018 to August 2023. Cycles with hormonal pre-treatment or pituitary suppression were excluded. Participants/materials, setting, methods Single euploid FRET cycles were included. Oral estradiol administration commenced on cycle-day 2/3. Estradiol, progesterone, and LH were measured at the start of endometrial preparation and up to 3 days before progesterone initiation, and the slope of LH was calculated. Patients were stratified in groups according to their LH values before progesterone administration, and the impact of LH on LBR and implantation rate was assessed. Logistic regression analysis was performed to adjust for potential confounders. Main results and the role of chance In total 639 cycles were included. Patients’ characteristics (mean+/-SD) were: age 33.2±5.9 years; BMI 27.5±4.9 kg/m2. The median duration of estrogen administration was 15 days (range: 11-27 days). The overall implantation rate and LBR were 65.9% (421/639) and 46.9% (300/639), respectively. Patients were stratified into six groups according to their LH levels prior to progesterone supplementation: <10th percentile (≤6mIU/ml, n = 57), p10th-p25th (>6 to ≤ 8.5mIU/ml, n = 81), p25th-p50th (>8.5 to ≤ 12.4mIU/ml, n = 176), p50th-p75th (>12.4 to ≤ 18.1mIU/ml, n = 180), p75th-p90th (>18.1 to ≤ 25.0mIU/ml, n = 91) and >p90th (>25.0mIU/ml, n = 54). A significant trend for higher LBR with increasing serum LH levels was observed (Cochran-Armitage Test, P = 0.041) but not for implantation rate (P = 0.158). Those with higher basal serum estradiol levels before estrogen supplementation had a steeper LH increase from basal to progesterone-supplementation day (0.40 mIU/mL higher per 10pmol/L increase in basal estradiol, P = 0.027). Regression analysis identified as independent predictors of LBR BMI (OR 0.96, 95%CI: 0.93-0.99) and embryo quality (CC vs. AA p < 0.001, CB vs. AA p = 0.027, BC vs. AA p = 0.013). Patients with steeper LH increases from estrogen to progesterone-supplementation day had higher LBR in both univariable (OR:1.27, 95%CI: 1.00–1.63, P = 0.052) and multivariable analyses (OR:1.26, 95%CI: 0.97–1.64, P = 0.085) but the difference didn’t reach statistical significance. Limitations, reasons for caution The retrospective design of the study is a limitation. Results should be interpreted with caution due to the small number of patients in the lowest and highest LH percentile groups. Wider implications of the findings The results of this study suggest that serum LH levels measured before progesterone supplementation may have an impact on the clinical outcome of artificial frozen-thawed blastocyst transfer cycles. Further studies with a higher sample size are necessary to confirm or refute our findings. Trial registration number not applicable

Establishment and evaluation of a premenstrual syndrome rat model induced by progesterone-withdrawal and emotional-stimulation

Premenstrual syndrome(PMS) lacks a highly consistent and feasible animal model that aligns with diagnostic and therapeutic standards in both traditional Chinese medicine(TCM) and western medicine, resulting in a lack of reliable experimental carriers for studying its pathogenesis and pharmacological effects. This study aims to systematically analyze the biological implications of PMS from the perspective of the "disease-syndrome-symptom" correlation and establish preparation and evaluation methods for an improved animal model of this disease. Firstly, clinical symptom gene sets related to the Qi stagnation syndromes due to liver depression and blood stasis in PMS in both modern medicine and TCM diagnostic standards were collected through GeneCards, DisGeNET, Mala-Cards, and the System of Foundational Diagnostic Association(SoFDA) database, as well as published literature. Based on the interaction information between genes, a "disease-syndrome-symptom" correlation network of PMS was established. Based on data mining results, an improved rat model of PMS was prepared by combining chronic restraint stress with the classical progesterone-withdrawal mo-del to simulate emotional depression caused by external environmental stimuli during the clinical onset process, inducing pathological damage from both physiological and emotional dimensions. The evaluation of the improved model before and after modification included open field experiment scores, organ indices, ovarian pathological changes, serum levels of estradiol(E_2), follicle-stimulating hormone/luteinizing hormone(FSH/LH), 5-hydroxytryptamine(5-HT), dopamine(DA), norepinephrine(NE), as well as coagulation parameters and hemorheology indexes. By calculating the degree, betweenness, and closeness centrality of nodes in the "disease-syndrome-symptom" correlation network, 163 core genes with topological importance were identified. Further biological function mining results indicated that core genes in PMS mainly participated in the regulation of the "nervous-endocrine-immune" system and pathways related to circulatory disorders. Mapping analysis of clinical phenotype symptom gene sets suggested significant correlations between core genes in PMS and depressive symptoms and pain symptoms caused by blood stasis. Compared with the simple progesterone withdrawal model, rats subjected to combined injections and restraint stress showed more significant abnormalities in open field experiment scores, ovarian tissue pathology, serum neurotransmitter levels of 5-HT and DA, as well as serum hormone levels of E_2 and FSH/LH. The modified modeling conditions exacerbated the pathological changes in blood rheology, coagulation function, and red blood cell morphology in model rats, confirming that the improved rat model could characterize the "nervous-endocrine-immune" system disorder and circulatory system disorders in the occurrence and progression of PMS, consistent with the clinical diagnostic and therapeutic standards of both TCM and western medicine. The establishment of the improved rat model of PMS can provide a reliable experimental carrier for elucidating the pathogenesis of PMS and discovering and evaluating therapeutic drugs. It also provides references for objectively reflecting the clinical characteristics of PMS in TCM and western medicine and precision treatment.

Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway

Ethnopharmacological relevanceZuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging. Aim of the studyTo examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway. Materials and methodsFemale Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs. ResultsAfter ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention.The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress.Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis.The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385. ConclusionsZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.

Mitigating effect of gallic acid on zinc oxide nanoparticles and arsenic trioxide-induced spermatogenesis suppression, testicular injury, hormonal imbalance, and immunohistochemical changes in rats.

The current study compared the effects of incorporated exposure to arsenic trioxide (As) and zinc oxide nanoparticles (ZnONPs) on male reproductive hormones, oxidative stress, and inflammatory biomarkers in adult rats to each metal alone. A defensive trial with gallic acid (GA) has also been studied. A total of 60 adult male Sprague Dawley rats were categorized into six groups: control, GA (20 mg/kg), ZnONPs (100 mg/kg), As (8 mg/kg), ZnONPs with As, and GA concurrently with ZnONPs and As at the same previous doses. The regimens were applied for 60 days in sequence. Current findings showed significant weight loss in all study groups, with testicular weights significantly decreased in the As and combined groups. Testosterone, follicular stimulating hormone, and luteinizing hormone serum levels were also considerably reduced, while serum levels of estradiol increased. Inducible nitric oxide synthase (iNOS) immunoexpression was significantly upregulated while proliferating cell nuclear antigen (PCNA) was downregulated. Moreover, there was a significant elevation of testicular malondialdehyde, reduction of testicular superoxide dismutase, and glutathione peroxidase with disruptive testes, prostate glands, and seminal vesicle alterations in all experimental groups with marked changes in the combined group. Additionally, the present results revealed the protective effects of GA on ZnONPs and As adverse alterations in rats. GA enhanced sperm picture, oxidant status, and hormonal profile. Also, it modulates iNOS and PCNA immunoexpression and recovers the histoarchitecture of the testes, prostate glands, and seminal vesicles. Ultimately, GA may be a promising safeguarding agent against ZnONPs and As-induced disturbances to reproductive parameters.

Characteristics of markers of ovarian reserve in women with transfusion-dependent beta thalassaemia major with a successful pregnancy outcome

Objective: Spontaneous fertility and successful pregnancies have been reported in well-chelated and transfused women with beta thalassaemia major (BTM) however majority of women are sub fertile due to hypogonadotropic hypogonadism (HH) and lack of ovulation. Little is known about the effect of iron overload on ovarian follicles and whether ovarian reserve is affected by the condition or treatment. The predictive value of markers of ovarian reserve in relation to live birth in this group of women remains unclear. The aim of this study was to characterize the markers of ovarian reserve in women with transfusion-dependent beta thalassaemia major who had at least one successful live birth. Study design: This is a retrospective study in which we collected data from 12 women with transfusion-dependent BTM and at least one successful live birth from our thalassaemia clinic between July 2007 to June 2022. Patient demographics, medical history, menstrual history, hormonal parameters (serum levels of FSH, oestradiol, TSH and AMH) and antral follicle count were recorded. Serum levels of ferritin, cardiac T2*, liver iron concentration and thyroid function results were recorded from clinic visit prior to either natural conception or assisted conception treatments. Results: There was a wide variation in serum levels of AMH and antral follicle counts amongst women with BTM who had a successful live birth. Low serum AMH levels were noted in 4 women with HH with a background of BTM (33.3%) as compared to the established normal ranges for women of similar age. Also, low AFC counts were noted in 7 women (out of which 6 had HH) with BTM (58.3%) as compared to the established normal ranges for women of similar age. Conclusion: Levels of serum AMH and antral follicle counts appeared lower in up to half the women with BTM and hypogonadotropic hypogonadism with a successful live birth as compared to established normal ranges for women of similar age suggesting that these markers may not accurately reflect the ovarian reserve for all in this group of women. There are limited data about the predictive value of contemporary markers ovarian reserve such as serum AMH and AFC levels in predicting successful fertility or pregnancy outcomes in women with transfusion dependent BTM and larger studies are needed.

Role of estradiol and C-reactive protein levels on genitourinary syndrome in menopausal women.

Menopause leads to decreased estradiol levels affecting tissue health and causing local inflammation in the genital organs and urinary tract. The rise of blood C-reactive protein (CRP) levels in menopausal women may indicate systemic inflammation associated with estradiol decline. The aim of this study was to determine the relationship between serum estradiol and CRP levels on genitourinary syndrome in menopausal women. A cross-sectional study was conducted among menopausal women who had not experienced menstruation for at least 12 consecutive months at Prof. dr. Chairuddin P. Lubis Hospital, Medan, Indonesia, in 2023. Estradiol and CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) and the presence of genitourinary syndrome was assessed using the Menopause-Specific Quality of Life (MENQOL) questionnaire. The mean levels of estradiol and CRP were compared to menopausal women with and without genitourinary syndrome with the Mann-Whitney test. To assess the correlation between estradiol and CRP levels, and between their levels with the presence of genitourinary symptoms, the Spearman correlation test was used. The genitourinary syndrome was reported in 25% of the total included menopausal women. Our data indicated that the mean estradiol levels were not significantly different between menopausal women with and without genitourinary syndrome (9.13±2.47 pg/mL vs 18.96±31.23 pg/mL, p=0.881). The mean serum CRP level of menopausal women with genitourinary syndrome (9.72±6.30 mg/L) was higher than that of women without the syndrome (2.09±1.26 mg/L) with p<0.001. In addition, serum CRP level, not estradiol, was correlated with the symptom score of genitourinary syndrome. This study highlights that to identify and manage genitourinary syndrome, monitoring of CRP levels is essential in menopausal women.

Correlation between sperm DNA fragmentation and methylation in male partners of couples with idiopathic recurrent pregnancy loss

With ∼50% recurrent pregnancy loss cases being termed idiopathic (iRPL), understanding of contribution of male factors to iRPL is still lacking. Higher prevalence of sperm DNA fragmentation index (DFI) and lower sperm 5-methylcytosine (5-mC) levels have been previously reported in male partners of iRPL couples and shed light on importance of the male gamete in maintenance of a successful pregnancy. The present study aimed to determine the serum sex steroid hormone levels, sperm DFI and 5-mC and correlation between them in male partners of fertile and iRPL couples. Further, correlation between sperm DFI and 5-mC with semen parameters and paternal age in both groups were determined. 36 male partners of fertile couples and 45 male partners of women experiencing iRPL were enrolled for this study and semen and blood samples were collected. Serum testosterone and estradiol levels were measured by ELISA; sperm DFI and global 5-mC were determined by TUNEL assay and ELISA respectively. Significantly higher serum testosterone levels were noted in the iRPL group (p = 0.028). Incidence of sperm DNA fragmentation was found to be higher in the iRPL study group but with no significance difference. No significant differences in sperm 5-mC values were noted. Upon correlation analysis within both groups, strong significant negative correlation of sperm DFI % and 5-mC % was observed in the control group (p < 0.001) but not the iRPL group (p = 0.249). Hence, we infer that with lower 5-mC levels in sperm genome, there is a higher incidence of sperm DFI in fertile men. However, this trend is not noted in men of iRPL group which could possibly be due to other underlying epigenetic alterations in genomic regions probably unsusceptible to fragmentation. On the other hand, no significant correlations of semen parameters, testosterone, estradiol and paternal age with sperm DFI and 5-mC were noted in both groups.

Therapeutic effects of curculigoside on cyclophosphamide-induced premature ovarian failure in mice

Objective The main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF). Method Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin–eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries. Results The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis. Conclusion CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis.

Association between sex hormones and erectile dysfunction in men without hypoandrogenism

In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Follow-Up Study of 17-β Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-β estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-β estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-β estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-β estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

THE EFFECT OF 4-VINYLCYCLOHEXENE DIEPOXIDE ON FEMALE NUTRIA (MYOCASTOR COYPUS) FERTILITY IN CAPTIVITY-A PILOT STUDY.

The nutria (Myocastor coypus) is a globally widespread invasive species. Attempts to eradicate nutria by shooting, poisoning, and trapping have been mostly unsuccessful, leading to calls for the development of new control methods. The compound 4-vinylcyclohexene diepoxide (VCD) is known to cause follicular atresia in mammals and may control conception when administered orally. It was hypothesized that VCD administered PO will cause follicular destruction in female nutria. VCD (250 mg/kg PO) was administered or coconut oil, as a control, to five nutria females each for 12 d. Sixty days following VCD exposure, males were introduced to the females. Over the following 7 mon, the effect of VCD on nutria fertility was assessed by conducting ultrasound monitoring to determine pregnancy status and measuring blood serum progesterone and estradiol levels. Finally, after performing ovariectomies, viable follicles were counted on histologic ovarian cortical sections. It was found that the female estrous cycles became synchronized, suggesting a Whitten effect in this species. Also, an increase in the females' serum progesterone levels following the introduction of males occurred, suggesting a male presence effect. Orally administered doses of 250 mg/kg VCD for 12 d had no significant effect on nutria pregnancy rates or on the number of follicles in the ovaries examined. Further studies, using a higher dose or longer administration period, are necessary to conclude whether orally administered VCD can be used as a contraceptive agent for nutria.

Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1β, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Estrogen and the estrogen receptor in ZSF1 rats with heart failure with preserved ejection fraction

Abstract Funding Acknowledgements None. Background Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women, so declining estrogen levels after menopause may be involved in genesis of the disease. Estrogen is cardio-protective, affecting blood pressure and vasodilatation and endothelial dysfunction is discussed as HFpEF pathomechanism. However, the potential connection between HFpEF and estrogen levels remains poorly understood. The well-established HFpEF ZSF1 rat model was used to analyze endothelial dysfunction, and a pronounced imbalance of the NO synthase substrates arginine and homoarginine was observed. Of note, estrogen levels in woman are directly and positively associated to homoarginine levels. Purpose We characterized serum estrogen levels and the expression of the estrogen receptor alpha (ERα) in the hearts of female ZSF1 HFpEF rats to investigate a possible contribution of estrogen signaling in HFpEF manifestation and to evaluate the suitability of this animal model in the context of estrogen and HFpEF. Methods In total, 12 obese ZSF1 rats with HFpEF (O-ZSF1) and 12 lean healthy ZSF1 rats (L-ZSF1) at 20 weeks of age and 5 animals of either phenotype aged 32 weeks were analyzed. Further, six O-ZSF1 rats were supplemented with homoarginine (hArg) when HFpEF was manifest and were observed up to 32 weeks of age. The manifestation of HFpEF was confirmed by echocardiography and determination of NT-proBNP by ELISA. Circulating estradiol (E2) in serum was determined using ELISA. Expression of the estrogen receptor alpha was determined by Western Blot analysis in the left ventricle (LV), septum and right ventricle (RV). Results Serum estradiol levels were similar in age-matched L-ZSF1 and O-ZSF1, but were ~2-fold increased at an age of 32 weeks compared to 20 weeks (p=0.002). The canonical ERα-66kDa was very weakly expressed in all tissues. ERα-45kDa expression in the LV was lower in O-ZSF1 at an age of 20 weeks (-46%, p=0.008) and at 32 weeks (-46%, p=0.002). ERα-45kDa expression in LV was 2-fold higher than in septum and 5-fold higher than in RV in rats aged 20 weeks (p&amp;lt;0.001). In RV, no differences in ERα-45kDa expression were observed. Supplementation of O-ZSF1 with hArg reestablished the ERα-45kDa expression in the LV (p=0.005 vs. O-ZSF1 without supplementation). Conclusion The manifestation and progression of HFpEF in ZSF1 rats is accompanied by a decrease of the ERα-45kDa expression in the LV, whereas the RV is not affected. Supplementation with homoarginine normalizes ERα-45kDa expression. The ERα-45kDa isoform was found to suppress the transcriptional activity of the classical ERα-66kDa isoform and to be an acute regulator of endothelial NO synthase in response to estrogen. These results suggest that altered ERα expression in the LV may represent a novel pathomechanism in HFpEF. In combination with decreasing estrogen levels in woman, adverse consequences for NO production in the LV seem likely.

Neurokinin B in the yellowtail kingfish (Seriola lalandi) and its potential role in controlling reproduction

The neurokinin B (NKB) system acts as a crucial modulator in the regulation of reproduction and feeding in mammals, however limited information is available in teleosts regarding its potential role in reproductive functions. Herein, we have identified its encoding gene, namely tachykinin 3 (tac3), in the yellowtail kingfish. The full-length tac3 cDNA sequence was 372 bp in size and encoded a 123-aa preprohormone, including two mature peptides, NKB and NKF. Tissue distribution analysis showed that tac3 was primarily expressed in the intestine of yellowtail kingfish. During embryonic development, the highest mRNA levels of tac3 were observed at stage 4 (16-cell) and stage 14 (newly-hatched larva). The peak of tac3 transcript levels was also noticed at 30 days post-hatching during early ontogeny. The physiological effects of NKB and NKF on expression of brain and pituitary genes along with plasma hormones levels were further analyzed by intraperitoneal injection. NKB exerted a stimulatory effect on gnrh1, gnrh2, gnih, and kiss2r mRNA levels, but suppressed kiss1r, gnihr, gal, gh, lhβ, and fshβ mRNA levels. An evident increase was observed on transcript levels of gnrh1, gnrh2, kiss1, kiss2, gnih, and gnihr after NKF treatment, whereas kiss1r, kiss2r, gh, lhβ, and fshβ mRNA levels were down-regulated. Moreover, NKF, but not NKB, reduced serum estradiol levels, and both of these two peptides suppressed serum 11-keto testosterone levels. Taken together, our results provide preliminary evidence that the NKB system participates in the control of reproduction in yellowtail kingfish via acting on brain, pituitary and gonadal hormones.

Ameliorative effect of rare ginsenosides on reproductive injury induced by cyclophosphamide in female rats: based on metabonomics

Objective: To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats. Methods: Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1β, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group. Results: Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased (P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1β [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased (P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased (P<0.01), serum FSH, IL-1β and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion: RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

Beneficial Effects of Probiotics Derived from Inonotus Obliquus on Menopausal Symptoms in Ovariectomized Mice

Physical debilitation and other health risks such as cardiovascular disease and osteoporosis often accompany decreased estrogen production in postmenopausal women. Phytoestrogens, natural compounds that functionally mimic estrogens, have emerged as a potential treatment method for hormonal dysregulation during menopause. Among these, chaga (Inonotus obliquus) extract has gained attention for its various health benefits, including anti-cancer and antioxidant properties. The aim of this study was to investigate the bone metabolic efficacy of lactic acid bacteria derived from I. obliquusin ovariectomized C57BL/6J female mice. The results demonstrated the estrogenic activity of probiotics derived from I. obliquus and its potential to alleviate osteoporosis symptoms by improving bone microstructure and density. Furthermore, probiotics derived from I. obliquus favored biochemical markers associated with a reduction in bone resorption. Additionally, effects on brain neurotransmitters and serum estradiol levels suggested its regulatory role in estrogen mimicry. These findings underscore the therapeutic potential of probiotics derived from I. obliquus in managing menopausal symptoms and thus warrant potential human investigation in improving bone health in postmenopausal women.

Beneficial Effects of Probiotics Derived from Inonotus Obliquus on Menopausal Symptoms in Ovariectomized Mice

Physical debilitation and other health risks such as cardiovascular disease and osteoporosis often accompany decreased estrogen production in postmenopausal women. Phytoestrogens, natural compounds that functionally mimic estrogens, have emerged as a potential treatment method for hormonal dysregulation during menopause. Among these, chaga (Inonotus obliquus) extract has gained attention for its various health benefits, including anti-cancer and antioxidant properties. The aim of this study was to investigate the bone metabolic efficacy of lactic acid bacteria derived from I. obliquusin ovariectomized C57BL/6J female mice. The results demonstrated the estrogenic activity of probiotics derived from I. obliquus and its potential to alleviate osteoporosis symptoms by improving bone microstructure and density. Furthermore, probiotics derived from I. obliquus favored biochemical markers associated with a reduction in bone resorption. Additionally, effects on brain neurotransmitters and serum estradiol levels suggested its regulatory role in estrogen mimicry. These findings underscore the therapeutic potential of probiotics derived from I. obliquus in managing menopausal symptoms and thus warrant potential human investigation in improving bone health in postmenopausal women.