Estrogen Concentrations Research Articles

Pain after oocyte retrieval in women with endometriosis undergoing fertility preservation or IVF

Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF? This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS). Women in the fertility preservation group were younger (32.1 ± 4.2 years versus 35.1 ± 4.1 years; P < 0.001), had a lower body mass index (22.8 ± 3.9 kg/m2 versus 24.6 ± 4.4 kg/m2; P < 0.001) and had a lower concentration of anti-Müllerian hormone (1.8 ± 1.5 ng/ml versus 2.15 ± 2.11 ng/ml; P = 0.026) in comparison with women in the IVF group. The oestrogen concentration on the day of ovulation trigger was higher in women in the fertility preservation group (2188 ± 1152 pg/ml versus 2081 ± 995 pg/ml; P = 0.004), and the prevalence rates of adenomyosis and digestive endometrial lesions were lower in women in the fertility preservation group (14% versus 29%, P < 0.001; 16% versus 25%, P = 0.003, respectively) compared with women in the IVF group. After oocyte puncture, more women in the fertility preservation group had an NRS pain score >3 (moderate to severe pain) compared with women in the IVF group (20% versus 14%; P = 0.018). The progestin-primed ovarian stimulation (PPOS) protocol was identified as an independent predictive factor of greater post-operative pain (adjusted OR 2.30, 95% CI 1.06-5.15; P = 0.039). Women with endometriosis undergoing fertility preservation reported more intense post-operative pain in the recovery room than women undergoing IVF. The PPOS protocol was an independent risk factor of intense pain (NRS pain score >3) in women with endometriosis, but further studies are needed to confirm this result.

Increased Expression of BCL6 in Women with Implantation Failure

Objectives: Progesterone (P4) expression failure and increased B-cell lymphoma 6 (BCL6) levels have been demonstrated in the endometrium of women withendometriosis and unexplained infertility. In the present work, we studied BCL6 (P4 inhibitor) expression in relation to different hormonal exposures of the endometrium during the implantation window, as a predictor of poor reproductive results in “in vitro fertilization” procedures. Materials and Methods: BCL6 was investigated in endometrial biopsies from four infertile patients from the Reproductive Medicine Unit, Clinicas University Hospital “José de San Martín”, Buenos Aires, Argentina, using immunohistochemical techniques. Results: Four patients without suspicion of endometriosis but recurrent implantation failure were included in the analysis. They were all evaluated during the window of implantation. Two of them were under an artificial supplemented cycle with estradiol and progesterone for a frozen thawed embryo transfer, one was under high concentrations of endogenous oestrogen and progesterone due to a controlled ovarian stimulation regimen for an assisted reproductive technique, and one had a natural menstrual cycle. All patients exceeded the threshold level of the HSCORE for BCL6 (1. 4). Conclusions: Abnormal endometrial expression of BCL6 participates in the development of P4 resistance in the endometrium. The BCL6 assay, performed prior to embryo transfer, could benefit women with suspected endometrial receptivity defects.

Menstrual Cycle Phase Has No Influence on Performance-Determining Variables in Endurance-Trained Athletes: The FENDURA Project.

This study aimed to investigate the effect of the MC and endogenous sex hormone concentrations on performance-determining variables in three distinct MC phases in endurance-trained females. Twenty-one eumenorrheic trained/highly trained endurance athletes completed a standardized test battery during the early follicular phase (EFP), ovulatory phase (OP), and midluteal phase (MLP) for either one ( n = 7) or two test cycles ( n = 14). MC phases were determined using calendar-based counting, urinary ovulation testing, and verified with serum hormone analysis. MCs were retrospectively classified as eumenorrheic or disturbed. Disturbed MCs were excluded from analysis. The test battery consisted of 4-6 × 5-min submaximal stages with stepwise speed increases, a 30-s all-out double-poling ski ergometer test, and a maximal incremental treadmill running test. At a group level, there was no effect of MC phase or the serum concentrations of estrogen and progesterone on peak oxygen uptake (V̇O 2peak ), oxygen uptake at 4 mmol·L -1 blood lactate concentration, time to exhaustion, running economy, or mean 30-s power output (MPO 30s ). Serum testosterone concentration was positively associated with MPO 30s ( P = 0.016). Changes in V̇O 2peak from EFP to MLP were inconsistent between individuals and across cycles. None of the measured performance-determining variables were influenced by MC phase or serum estrogen or progesterone concentrations. Although some individual patterns could be observed, there was no indication that any single MC phase is consistently associated with improved or impaired V̇O 2peak on a group level.

Patterns of Sleep Duration and Metabolic Biomarkers Across the Menstrual Cycle.

Along the menstrual cycle, associations between inconsistent sleep duration and levels of metabolic biomarkers are uncertain and could involve fluctuations in estrogen concentrations. To examine associations between patterns of sleep duration and metabolic biomarkers across two menstrual cycles within a cohort of premenopausal women. The BioCycle Study was conducted in New York between 2005-2007, enrolling 259 premenopausal women over two menstrual cycles. This micro-longitudinal cohort study involved intensive data collection including daily sleep diaries and biomarker assessments of leptin, insulin, and glucose at 16 key points timed to menstrual cycle phases. We considered dynamic sleep duration, as hours slept one night or as mean hours slept during the two nights prior to each biomarker assessment. Variability in habitual sleep duration, i.e., reported daily sleep duration, summarized across both menstrual cycles. Variation in habitual sleep duration was computed using L-moments, a robust version of dispersion, skewness, and kurtosis. To examine associations between patterns of sleep duration and metabolic biomarkers, we fitted a series of linear mixed models with random intercepts and inverse probability weighting. These models were adjusted for potential demographic, lifestyle, health confounders, and menstrual cycle phase. Sleep duration one night or two nights prior to clinic visits were not associated with metabolic biomarker measures we assessed. However, overall variability (dispersion) in habitual sleep duration was associated with lower mean insulin HOMA-IR levels, but not glucose. Moreover, extreme short or long bouts of sleep duration was associated with higher mean levels of leptin, insulin, and HOMA-IR. These data suggest that variation in habitual sleep duration along the menstrual cycle may be associated with metabolic function.

Estrogen and Progesterone Receptors Are Dysregulated at the BPH/5 Mouse Preeclamptic-Like Maternal-Fetal Interface.

The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and misexpression of placental estrogen and progesterone receptors (ER and PR, respectively). However, existing research is vastly confined to third trimester preeclamptic placentas. Consequently, the placental-uterine molecular crosstalk and the dynamic ER and PR expression pattern in the peri-conception period remain overlooked. Herein, our goal was to use the BPH/5 mouse to elucidate pre-pregnancy and early gestation Er and Pr dynamics in a preeclamptic-like uterus. BPH/5 females display low circulating estrogen concentration during proestrus, followed by early gestation hypoestrogenemia, hyperprogesteronemia, and a spontaneous preeclamptic-like phenotype. Preceding pregnancy, the gene encoding Er alpha (Erα, Esr1) is upregulated in the diestrual BPH/5 uterus. At the peak of decidualization, Esr1, Er beta (Erβ, Esr2), and Pr isoform B (Pr-B) were upregulated in the BPH/5 maternal-fetal interface. At the protein level, BPH/5 females display higher percentage of decidual cells with nuclear Erα expression, as well as Pr downregulation in the decidua, luminal and glandular epithelium. In conclusion, we provide evidence of disrupted sex hormone signaling in the peri-conception period of preeclamptic-like pregnancies, potentially shedding some light onto the intricate role of sex hormone signaling at unexplored timepoints of human preeclampsia.

Pathogenesis of viral infections during pregnancy.

SUMMARYViral infections during pregnancy are associated with significant adverse perinatal and fetal outcomes. Pregnancy is a unique immunologic and physiologic state, which can influence control of virus replication, severity of disease, and vertical transmission. The placenta is the organ of the maternal-fetal interface and provides defense against microbial infection while supporting the semi-allogeneic fetus via tolerogenic immune responses. Some viruses, such as cytomegalovirus, Zika virus, and rubella virus, can breach these defenses, directly infecting the fetus and having long-lasting consequences. Even without direct placental infection, other viruses, including respiratory viruses like influenza viruses and severe acute respiratory syndrome coronavirus 2, still cause placental damage and inflammation. Concentrations of progesterone and estrogens rise during pregnancy and contribute to immunological adaptations, placentation, and placental development and play a pivotal role in creating a tolerogenic environment at the maternal-fetal interface. Animal models, including mice, nonhuman primates, rabbits, and guinea pigs, are instrumental for mechanistic insights into the pathogenesis of viral infections during pregnancy and identification of targetable treatments to improve health outcomes of pregnant individuals and offspring.

Correlation of Metabolic and Ionic Components of Follicular Fluid with Estrogen Concentration

This study was aimed to assess the correlation between the metabolic and ionic composition of ovarian follicular fluid and its relationship to the concentration of estrogen and prolactin hormones as the follicle size changes in the local female cows. Ovaries were collected (80 ovaries) from non- pregnant 40 adult females cow at Hilla slaughterhouse at Babil province. The gathered ovaries were transported to the laboratory within two hours. Follicular fluid was pulled from small (2-5 mm) follicles, medium (6-10 mm), and large (11-20 mm) follicles, then it stored at 5 ° C until assayed. Follicular fluid samples were analyzed for metabolites composition of (cholesterol, total protein, and glucose), and ionic composition (calcium, phosphorus, copper, magnesium, zinc) ,and hormone concentration ( estrogen and prolactin). The results of the study showed that the total protein and glucose concentrations were increased significantly(p&gt; 05.0) with increased of follicle size. The study also showed the calcium, copper, and phosphorus concentration were increased significantly(p&gt; 05.0) with changes of follicular size, as well as the estrogen concentration was significantly increased (p &gt; 05.0) With increased follicular size. A significantly (p&gt; 05.0) correlation was found between both magnesium, zinc ions, and estrogen hormone.

Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.

Occurrence, spatial distribution, risk assessment, and management of environmental estrogens in surface waters of the Taihu basin

Environmental context Environmental estrogens can disrupt the normal functioning of endocrine systems, and their occurrence in drinking water sources could cause potential health risk. We investigated concentrations of four estrogens in the lakes from the Taihu Basin, and found that BPA and EE2 were elevated in some sites. However, concentrations of all four environmental estrogens were below the national standards, and caused no health threat to local population. Rationale The Taihu Basin is a critical freshwater ecosystem susceptible to contamination from various anthropogenic activities. Environmental estrogens (also known as endocrine disrupting chemicals, EDCs) are exogenous substances that can disrupt the normal functioning of endocrine systems. The contamination of water by EDCs is primarily caused by effluents from sewage treatment plants and livestock poultry farms. In this study, we assessed the spatial distribution and potential risks of environmental estrogens in surface water in the Taihu basin. Various statistical evaluations were employed to establish connections between measured concentration of heavy elements, estrogens and physicochemical parameters, to identify potential sources of these contaminants. Methodology Water samples from 44 sampling points in five lakes in Suzhou were taken for evaluation of environmental estrogens. Gas chromatography–mass spectrometry was used for identification of concentrations of estrone (E1), estradiol (E2), ethinyl estradiol (EE2) and bisphenol A (BPA). Inductively coupled plasma–mass spectrometry was employed to identify heavy element concentrations in water samples. Results Environmental estrogen concentrations were detected ranging from 0.001 to 209 ng L–1, with the highest attributed to BPA, whereas E1, E2 and EE2 were comparatively lower. Correlation evaluation between environmental estrogens, physicochemical parameters and heavy element contents revealed a positive correlation (P &lt; 0.05) between the total chromium and environmental estrogen contents. Consequently, the risk entropy value of Shanghu Lake exceeded 0.5, indicating a potentially high risk of estrogenic activity. Discussion The widespread distribution and high concentrations of BPA in freshwater raise urgent concerns, highlighting the need for frequent monitoring of environmental estrogens in surface waters throughout the year to mitigate potential risks in the future. Our results suggest that a potential estrogen risk exists in the Shanghu Lake in the Taihu basin. Potential treatment methods for endocrine disruptors have been proposed, which could provide actionable plans for stakeholders.

Exploratory Review of the Takotsubo Syndrome and the Possible Role of the Psychosocial Stress Response and Inflammaging.

Takotsubo syndrome (TTS) is a cardiomyopathy that clinically presents as a transient and reversible left ventricular wall motion abnormality (LVWMA). Recovery can occur spontaneously within hours or weeks. Studies have shown that it mainly affects older people. In particular, there is a higher prevalence in postmenopausal women. Physical and emotional stress factors are widely discussed and generally recognized triggers. In addition, the hypothalamic-pituitary-adrenal (HPA) axis and the associated glucocorticoid-dependent negative feedback play an important role in the resulting immune response. This review aims to highlight the unstudied aspects of the trigger factors of TTS. The focus is on emotional stress/chronic unpredictable mild stress (CUMS), which is influenced by estrogen concentration and noradrenaline, for example, and can lead to changes in the behavioral, hormonal, and autonomic systems. Age- and gender-specific aspects, as well as psychological effects, must also be considered. We hypothesize that this leads to a stronger corticosteroid response and altered feedback of the HPA axis. This may trigger proinflammatory markers and thus immunosuppression, inflammaging, and sympathetic overactivation, which contributes significantly to the development of TTS. The aim is to highlight the importance of CUMS and psychological triggers as risk factors and to make an exploratory proposal based on the new knowledge. Based on the imbalance between the sympathetic and parasympathetic nervous systems, transcutaneous vagus nerve stimulation (tVNS) is presented as a possible new therapeutic approach.

Graphene Oxide, Carbon Nanotubes, and Polyelectrolytes-Based Impedanciometric E-Tongue for Estrogen Detection in Complex Matrices.

Currently, it is necessary to maintain the quality of aquifers and water bodies, which means the need for sensors that detect molecules as emerging pollutants (EPs) at low concentrations in aqueous complex solutions. In this work, an electronic tongue (e-tongue) prototype was developed to detect 17β-estradiol in tap water. To achieve such a prototype, an array of sensors was prepared. Each sensor consists of a solid support with interdigitated electrodes without or with thin films prepared with graphene oxide, nanotubes, and other polyelectrolytes molecules adsorbed on them. To collect data from each sensor, impedance spectroscopy was used to analyze the electrical characteristics of samples of estrogen solutions with different concentrations. To analyze the collected data from the sensors, principal components analysis (PCA) method was used to create a three-dimensional plane using the calculated principal components, namely PC1 and PC2, and the estrogen concentration values. Then, damped least squares (DLS) was used to find the optimal values for the hyperplane calibration, as the sensitivity of this e-tongue was not represented by a straight line but by a surface. For the collected data, from nanotubes and graphene oxide sensors, a calibration curve for concentration given by the 10PC1×0.492-PC2×0.14-14.5 surface was achieved. This e-tongue presented a detection limit of 10-16 M of 17β-estradiol in tap water.

Exosomes derived from mesenchymal stem cells attenuate NLRP3-related pyroptosis in autoimmune premature ovarian insufficiency via the NF-κB pathway

Research questionWhat is the effect of exosomes derived from bone marrow mesenchymal stem cells (MSC-Exos) on the pyroptosis and recovery of granulosa cells in autoimmune premature ovarian insufficiency (POI)? DesignIn vitro, KGN cells were exposed to interferon-gamma to simulate immune injury. Samples were collected after a 48 h incubation with MSC-Exos (30 μg/ml). The cell viability, secretion of oestrogen and expression of key molecules in pyroptosis and the nuclear factor kappa B (NF-κB) pathway were tested. In vivo, the BALB/c mouse model of autoimmune POI model induced by zona pellucida glycoprotein 3 was used. Fertility testing and sample collection were applied 4 weeks after the ovarian subcapsular injection of MSC-Exos (150 μg for each ovary). Hormone concentration measurements, follicle counting and pyroptotic pathway analyses were conducted for each group. ResultsIn vitro, MSC-Exos significantly promoted the proliferation rate and secretion of oestrogen, while at the same time suppressing apoptosis and pyroptosis. In vivo, exosomal treatment normalized the irregular oestrous cycles, rescued the follicular loss and increased the pregnancy rate and number of offspring in POI mice. Elevated serum concentrations of oestrogen and anti-Müllerian hormone, as well as decreased concentrations of FSH and interleukin-1β, were shown. Furthermore, MSC-Exos down-regulated the expression of the NLRP3/Casp1/GSDMD pathway and inhibited activation of the NF-κB pathway. ConclusionsThese findings demonstrate for the first time that MSC-Exos exert a significant effect on restoring ovarian function in autoimmune POI in vivo and in vitro by suppressing the NLRP3/Casp1/GSDMD pathway and pyroptosis. The NF-κB pathway may contribute to the regulation of NLRP3-related pyroptosis.

Effect of supplementing algae to breeding and early gestation first calf heifers on growth and reproduction.

Fat supplementation has potential to improve reproductive performance and increase pregnancy rates in cattle by increasing the energy density of the diet. However, some of the positive effects of fat seem to be influenced by the type of fatty acid fed. Docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) are long-chain n-3 poly-unsaturated fatty acids (PUFA) that have important biological effects on reproduction through their involvement in hormone and series 3 prostaglandin synthesis. Ruminant tissues are naturally almost devoid of n-3 long-chain PUFA, specifically EPA and DHA. Algae biomass provides a consistent source of DHA and EPA that could be fed to alter hormonal profiles and improve reproduction of beef heifers. Eighty-eight Angus × Simmental heifers (427 ± 1.8kg body weight [BW]) were blocked by BW and allotted to 2 treatments (44/treatment, 4 pens/treatment, 11 heifers/pen). Control heifers were fed a diet that contained (dry matter [DM] basis) 52.8% mixed grass silage, 32% corn silage, and 15.2% concentrate. DHAgold (49% fat; 21.8% DHA; DSM Inc.) was included in the algae diet at 1.65% DM, replacing equal parts of corn and DDGS. Diets were formulated to contain 12% crude protein and 0.85 Mcal/kg net energy for gain (NEg). Heifers were fed treatment diets from 54 d prior to the breeding season through the first trimester. Follicular fluid was collected on day 47 for hormonal analysis. Artificial insemination (AI) was from days 54 to 77. Heifers that did not get pregnant to AI were removed from the study on day 109 and placed with a bull. The study ended on day 180. Data were analyzed using the MIXED procedure of SAS. During the pre-breeding period, algae heifers had lesser dry matter intake (P = 0.006) compared to control heifers. Heifers supplemented with algae had a greater average daily gain (P = 0.03) during the breeding period and BW tended (P = 0.06) to be greater for algae compared to control heifers on day 98 and was greater on day 180 (P = 0.03). Dominant follicle diameter and follicular estrogen concentration were unaffected by treatment (P ≥ 0.12). Follicular insulin-like growth factor-1 was greater in algae compared to control heifers (P = 0.03). First service conception rate did not differ between treatments (P = 0.67); however, second service and overall conception were lesser (P ≤ 0.03) in algae compared to control heifers. These data suggest supplementing DHA-rich algae improved growth but decreased conception rates of primiparous beef females.

Combination of androgen and estrogen improves asthma by mediating Runx3 expression.

Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4+ T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3. Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma. Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression. Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.

Effects of Pasturella Multocida B:2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes.

Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Fecal metabolite and blood steroid concentration patterns in relation to reproductive behavior during the ovarian cycle of African lions (Panthera leo)

To develop successful ex-situ breeding programs for the conservation of threatened wildlife, an understanding of reproductive endocrinology in the species of interest is essential. Fecal hormone metabolite patterns are widely used in this regard, but limited information is available regarding how these reflect blood hormone profiles. This study aimed to longitudinally monitor and compare circulating progestagen (sP) and estrogen (sE) concentrations, as well as fecal progestagen (fPM) and estrogen (fEM) metabolite concentrations with observed reproductive behaviors of African lionesses. For 18 months, blood sampling (n = 309) from five captive lionesses took place 1–7 times per week during positive reinforcement training. In parallel, over a period of 9 months, fecal samples (n = 129) from four of these lionesses were searched for daily and collected when found. Daily behavioral monitoring of all females enabled classification of reproductive stage according to presence/absence of characteristic behavioral events (i.e., “allowing mount”, “copulation”, “flirting run”, “lordosis”, “purring”, and “rolling”). Competitive enzyme immunoassays were used for steroid quantification. In total, 11 an-ovulatory and 16 ovulatory cycles (7 pregnancies and 9 pseudo-pregnancies) were assessed. When compared, the pattern of fecal hormone metabolite concentrations matched reproductive behavior more reliably than circulating steroid concentrations. Both sP and fPM patterns were correlated (n = 51; r = 0.86) and enabled identification of luteal phases, which helped to distinguish between pregnant and non-pregnant females. In contrast, detection of estrus by measurement of sE and fEM was not accurate regardless of the matrix evaluated.

Alkylphenols disrupt estrogen homeostasis via diradical cross-coupling reactions: A novel pathway of endocrine disruption

Estrogen, being an essential class of sex hormone, is an important target of endocrine disruption chemicals. It is well known that environmental disruptors could activate or inhibit estrogen receptors, acting as agonists or antagonists, and thus affect the circulating estrogen concentrations. Here, we report enzyme-mediated diradical cross-coupling reactions between alkylphenols (e.g., 2,4-di-tert-butylphenol [DBP], 4-nonylphenol [4-NP], and 4-tert-octylphenol [4-t-OP]) and estrogens (e.g., estradiol [E2]) that generate coupling metabolites and disrupt estrogen homeostasis. Among the phenolic xenobiotics, the screening of metabolic products revealed that alkylphenols had the highest reaction activities and generated coupling metabolites with high abundances (DBP-O-E2, 4-t-OP-O-E2, and 4-NP-O-E2). The coupling reactions were catalyzed by cytochrome P450 3A4 (CYP3A4) and verified by the detection of the coupling products in general populations. In vitro and in vivo exposures together with CYP3A4 inhibition demonstrated that cross-coupling reactions of phenols and E2 significantly reduced the normal levels of E2. We further established a unique spin-trapping-based high-throughput screening method to show the existence of diradicals in the coupling reaction. Density functional theory calculations revealed that spin aromatic delocalization was the fundamental cause of the high rebound barrier and sufficient lifetime of phenoxy radicals that enabled phenolic cross-coupling triggered by cytochrome P450. The identified mechanistic details for diradical cross-coupling reactions provide a novel pathway for phenolic chemicals to disrupt estrogen homeostasis.

A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle.

The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

The differences of electrical resistance values of vaginal mucus (ERVM) in yearling and mature saanen goats

It has been reported that during the oestrous cycle, an increase in the volume of cervical mucus occurs due to the influence of high oestrogen concentration on vaginal vasodilation, leading to a decrease in the electrical resistance of vaginal mucus (ERVM) as the goat approaches estrus. The present study aims to understand the differences between yearling (n:14) and mature (n:22) Saanen goats when continuous measurements of ERVM were taken by using the digital Draminski® device (Draminski Electronics, Poland). Oestrus was synchronized using intravaginal sponges and the ERVM measurement was taken every 6 hours right after the sponge removal until insemination. The results indicate that ERVM measurements for mature Saanen goats were significantly lower at 0, 6, 12, 30, 36, and 42 hours compared to those of yearling Saanen goats. Additionally, within the yearling Saanen group, there was a significant difference between the measurement taken at the 18th hour and the measurements taken at other time points. Furthermore, as goats approached estrus, the differences in ERVM measurements between mature and yearling Saanen goats disappeared. Based on these results, the ERVM values in yearling Saanen goats can be reliably used for predicting time of estrus, while a more cautious approach should be taken for mature Saanen goats.

Comparative characteristics of healthy pregnant women and non-healthy pregnant women

We carried out a systematic search by using a literature about the issue of our interest in the PubMed and Scopus search databases. We systematically searched the literature published from December 1, 2019 to July 30, 2021 across multiple databases including PubMed, Web of Science, Google Scholar and the WHO COVID-19 database using the following keywords: “COVID-19” and “pregnancy”. Filter by date: March 1, 2020-until March 1, 2021. We have made a review of the literature on the issue of our interest in the PubMed and Scopus search databases. Based on our understanding, we want to present a small literary review. Changes in the cardiorespiratory and immune systems during pregnancy increase woman's susceptibility to severe infection and hypoxic compromise, but at the same time they may also delay diagnosis and source control in those who have only mild upper respiratory symptoms such as sore throat and nasal congestion; the latter are observed in 5% of patients with COVID-19. With gestational rhinitis, it should also be noted that in pregnant women the content of estrogen, β-estradiol increases, which increases the reactivity of the immune system. Therefore, the intensity of seizures during gestation can increase significantly. However, a high con-centration of estrogen disrupts vascular motility, causing vasomotor rhinitis during pregnancy, usually affects a fifth of healthy women in late pregnancy and leads to severe nasal congestion and rhinorrhea; these signs can mask the symptoms of COVID-19, leading to uncontrolled viral shedding and trans-mission. Dyspnea occurs in 18% of patients with COVID-19.