4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway.

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

Estrogen treatment in combination with pyruvate kinase M2 inhibition precipitate significant cumulative antitumor effects in colorectal cancer.

It is well established that pyruvate kinase M2 (PKM2) activity contributes to metabolic reprogramming in various cancers, including colorectal cancer (CRC). Estrogen or 17ß-estradiol (E2) signaling is also known to modulate glycolysis markers in cancer cells. However, whether the inhibition of PKM2 combined with E2 treatment could adversely affect glucose metabolism in CRC cells remains to be investigated. First, we confirmed the metabolic plasticity of CRC cells under varying environmental conditions. Next, we identified glycolysis markers that were upregulated in CRC patients and assessed in vitro mRNA levels following E2 treatment. We found that PKM2 expression, which is highly upregulated in CRC clinical samples, is not altered by E2 treatment in CRC cells. In this study, glucose uptake, generation of reactive oxygen species (ROS), lactate production, cell viability, and apoptosis were evaluated in CRC cells following E2 treatment, PKM2 silencing, or a combination of both. Compared to individual treatments, combination therapy resulted in a significant reduction in cell viability and enhanced apoptosis. Glucose uptake and ROS production were markedly reduced in PKM2-silenced E2-treated cells. The data presented here suggest that E2 signaling combined with PKM2 inhibition cumulatively targets glucose metabolism in a manner that negatively impacts CRC cell growth. These findings hold promise for novel therapeutic strategies targeting altered metabolic pathways in CRC.

Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.

The endometrium is crucial for the perpetuation of human species. It is a complex and dynamic tissue lining the inner wall of the uterus, regulated throughout a woman's life based on estrogen and progesterone fluctuations. During each menstrual cycle, this multicellular tissue undergoes cyclical changes, including regeneration, differentiation in order to allow egg implantation and embryo development, or shedding of the functional layer in the absence of pregnancy. The biology of the endometrium relies on paracrine interactions between epithelial and stromal cells involving complex signaling pathways that are modulated by the variations of estrogen and progesterone levels across the menstrual cycle. Understanding the complexity of estrogen and progesterone receptor signaling will help elucidate the mechanisms underlying normal reproductive physiology and provide fundamental knowledge contributing to a better understanding of the consequences of hormonal imbalances on gynecological conditions and tumorigenesis. In this narrative review, we delve into the physiology of the endometrium, encompassing the complex signaling pathways of estrogen and progesterone.

The Effects of Testosterone on Hypothalamic and Serum Oxytocin Levels Are Affected by the Estrogen Milieu in Female Rats.

Previous studies have suggested that the effects of androgens on body weight (BW) and appetite are affected by the estrogen milieu in females; however, the mechanism underlying these effects remains unclear. We hypothesized that androgens may affect endogenous oxytocin (OT), which is a hypothalamic anorectic factor, and that these effects of androgens may be altered by the estrogen milieu in females. To investigate this hypothesis, in the present study, we examined the effects of testosterone on peripheral and central OT levels in ovariectomized female rats that did or did not receive estradiol supplementation. Ovariectomized female rats were randomly divided into non-estradiol-supplemented or estradiol-supplemented groups, and half of the rats in each group were concurrently supplemented with testosterone (i.e., rats were divided into four groups, n = 7 per each group). We also measured peripheral and central OT receptor (OTR) gene expression levels. As a result, we found that testosterone increased serum and hypothalamic OT levels and OT receptor mRNA levels in non-estradiol-supplemented rats, whereas it had no effects on these factors in estradiol-supplemented rats. In addition, testosterone reduced food intake, BW gain, and fat weight in non-estradiol-supplemented rats, whereas it did not have any effects on BW, appetite, or fat weight in estradiol-supplemented rats. These findings indicate that the effects of androgens on OT may be affected by the estrogen milieu, and elevated OT levels may be related to the blunting of appetite and prevention of obesity under estrogen-deficient conditions.

The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs.

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor ß (ESR2/Erß), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-ß belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis.

Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates.

Many persistent organic pollutants (POPs) are suspected endocrine disruptors and it is important to investigate their effects at low concentrations relevant to human exposure. Here, the OECD test guideline #456 steroidogenesis assay was downscaled to a 96-well microplate format to screen 24 POPs for their effects on viability, and testosterone and estradiol synthesis using the human adrenocortical cell line H295R. The compounds (six polyfluoroalkyl substances, five organochlorine pesticides, ten polychlorinated biphenyls and three polybrominated diphenyl ethers) were tested at human-relevant levels (1 nM to 10 µM). Increased estradiol synthesis, above the OECD guideline threshold of 1.5-fold solvent control, was shown after exposure to 10 µM PCB-156 (153%) and PCB-180 (196%). Interestingly, the base hormone synthesis varied depending on the cell batch. An alternative data analysis using a linear mixed-effects model that include multiple independent experiments and considers batch-dependent variation was therefore applied. This approach revealed small but statistically significant effects on estradiol or testosterone synthesis for 17 compounds. Increased testosterone levels were demonstrated even at 1 nM for PCB-74 (18%), PCB-99 (29%), PCB-118 (16%), PCB-138 (19%), PCB-180 (22%), and PBDE-153 (21%). The MTT assay revealed significant effects on cell viability after exposure to 1 nM of perfluoroundecanoic acid (12%), 3 nM PBDE-153 (9%), and 10 µM of PCB-156 (6%). This shows that some POPs can interfere with endocrine signaling at concentrations found in human blood, highlighting the need for further investigation into the toxicological mechanisms of POPs and their mixtures at low concentrations relevant to human exposure.

Meta-analysis of the association between sex hormones and pulmonary fibrosis.

BACKGROUND: This study aimed to investigate the association between sex hormones and the risk of pulmonary fibrosis by conducting a meta-analysis of previously published studies. METHODS: We executed a comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases to locate pertinent studies published up to April 2024. We included studies that reported the association between sex hormones and the risk of pulmonary fibrosis. Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of 10 articles, encompassing 1371 patients, were finally incorporated in this meta-analysis. Based on the evaluation of the included studies, it was observed that the levels of dehydroepiandrosterone sulfate (DHEA-S) (pooled SMD: -0.72, 95% CI: -1.21 to -0.24, p < 0.001), testosterone (pooled SMD: -1.25, CI: -2.39 and -0.11, p < 0.001) and estrogen (pooled SMD: -0.56, 95% CI: -0.96 to -0.15, p < 0.001) were significantly lower in patients with pulmonary fibrosis, whereas the levels of luteinizing hormone (LH) remained unaffected. Publication bias was ruled out through funnel plots. CONCLUSION: This meta-analysis indicates that reduced levels of DHEA-S, testosterone, estrogen may serve as potential risk factors for pulmonary fibrosis. There is a pressing need for additional studies to confirm this association and explore the underlying biological mechanisms. Clinicians should recognize the potential influence of sex hormones in the etiology of pulmonary fibrosis and consider this aspect during the patient management process.

A Review of the Role of Estrogens in Olfaction, Sleep and Glymphatic Functionality in Relation to Sex Disparity in Alzheimer's Disease.

Several risk factors contribute to the development of Alzheimer's disease (AD), including genetics, metabolic health, cardiovascular history, and diet. It has been observed that women appear to face a higher risk of developing AD. Among the various hypotheses surrounding the gender disparity in AD, one pertains to the potential neuroprotective properties of estrogen. Compared to men, women are believed to be more susceptible to neuropathology due to the significant decline in circulating estrogen levels following menopause. Studies have shown, however, that estrogen replacement therapies in post-menopausal women do not consistently reduce the risk of AD. While menopause and estrogen levels are potential factors in the elevated incidence rates of AD among women, this review highlights the possible roles estrogen has in other pathways that may also contribute to the sex disparity observed in AD such as olfaction, sleep, and glymphatic functionality.

The epithelial Na+ channel (ENaC) in ovarian granulosa cells modulates Ca2+ mobilization and gonadotrophin signaling for estrogen homeostasis and female fertility.

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.

[Retrospective study on the impact of penile corpus cavernosum injection test on penile vascular function].

OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted. RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED. CONCLUSION: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.

Exploring the role of estrogen and progestins in breast cancer: A genomic approach to diagnosis.

Breast cancer (BC) is the most common cancer among women and a major cause of death from cancer. The role of estrogen and progestins, including synthetic hormones like R5020, in the development of BC has been highlighted in numerous studies. In our study, we employed machine learning and advanced bioinformatics to identify genes that could serve as diagnostic markers for BC. We thoroughly analyzed the transcriptomic data of two BC cell lines, T47D and UDC4, and performed differential gene expression analysis. We also conducted functional enrichment analysis to understand the biological functions influenced by these genes. Our study identified several diagnostic genes strongly associated with BC, including MIR6728, ENO1-IT1, ENO1-AS1, RNU6-304P, HMGN2P17, RP3-477M7.5, RP3-477M7.6, and CA6. The genes MIR6728, ENO1-IT1, ENO1-AS1, and HMGN2P17 are involved in cancer control, glycolysis, and DNA-related processes, while CA6 is associated with apoptosis and cancer development. These genes could potentially serve as predictors for BC, paving the way for more precise diagnostic methods and personalized treatment plans. This research enhances our understanding of BC and offers promising avenues for improving patient care in the future.

Oestrogen Represses Noggin Expression by Interfering With BMP/Smad Signalling in ER Positive Breast Cancer.

BACKGROUND/AIM: As an antagonist of bone morphogenetic protein (BMP), Noggin facilitates osteolytic bone metastases from breast cancer. The present study aimed to further dissect its role in oestrogen receptor (ER) positive breast cancer. MATERIALS AND METHODS: Noggin expression in ER positive breast cancer cell lines (MCF-7 and T-47D) was determined under conditions of oestrogen deprivation and treatment with 17-ß-oestradiol (E2). Activation of Smad1/5/8 in the oestrogen-regulated Noggin was examined using recombinant human BMP7 (rhBMP7) and a BMP receptor inhibitor (LDN-193189). The influence of Noggin on cellular functions was evaluated in MCF-7 and T-47D cell lines. Responses to tamoxifen and chemotherapy drugs were determined in MCF-7 and T-47D cells with Noggin over-expression using MTT assay. RESULTS: Noggin expression was negatively correlated with ERα in breast cancers. Noggin was up-regulated upon oestrogen deprivation, an effect that was eliminated by E2 Furthermore, increased levels of phosphorylated Smad1/5/8 were observed in the oestrogen-deprived MCF-7 and T-47D cells, which was prevented by E2 and LDN-193189, respectively. BMP7-induced Noggin expression and activation of Smad1/5/8 was also prevented by E2 and LDN-193189. Noggin over-expression resulted in an increase in the proliferation of both MCF-7 and T-47D cells. MCF-7 and T-47D cells over-expressing Noggin exhibited a good tolerance to tamoxifen (TAM), DTX, and 5-FU, but the percentage of viable cells was higher compared with the controls. CONCLUSION: Noggin expression can be repressed by oestrogen through inference with the BMP/Smad signalling. Over-expression of Noggin promotes the proliferation of MCF-7 and T-47D cells, contributing to drug resistance.

Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance.

The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC.

Potential Differences in Psychedelic Actions Based on Biological Sex.

The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence.

Sex differences in airway disease: estrogen and airway surface liquid dynamics.

Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory airway diseases such as cystic fibrosis (CF) and asthma display a clear male advantage in post-puberty while a female benefit is observed in asthma during the pre-puberty years. The influence of menstrual cycle stage and pregnancy on the frequency and severity of pulmonary exacerbations in CF and asthma point to a role for sex steroid hormones, particularly estrogen, in underpinning biological sex differences in these diseases. There are many ways by which estrogen may aggravate asthma and CF involving disturbances in airway surface liquid (ASL) dynamics, inappropriate hyper-immune and allergenic responses, as well as exacerbation of pathogen virulence. The deleterious effect of estrogen on pulmonary function in CF and asthma contrasts with the female advantage observed in airway diseases characterised by pulmonary edema such as pneumonia, acute respiratory distress syndrome (ARDS) and COVID-19. Airway surface liquid hypersecretion and alveolar flooding are hallmarks of ARDS and COVID-19, and contribute to the morbidity and mortality of severe forms of these diseases. ASL dynamics encompasses the intrinsic features of the thin lining of fluid covering the airway epithelium which regulate mucociliary clearance (ciliary beat, ASL height, volume, pH, viscosity, mucins, and channel activating proteases) in addition to innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, and metabolism). Estrogen regulation of ASL dynamics contributing to biological sex differences in CF, asthma and COVID-19 is a major focus of this review.

Sex differences exist in many airway diseases in which females have either worse or better health outcomes. These include cystic fibrosis (CF) and asthma where females post-puberty have more frequent lung exacerbations and higher mortality. Lung infections and difficulty in breathing become worse in post-puberty in females and during the ovulation period of the menstrual cycle, and in pregnancy, indicating a role for sex hormones in underpinning sex differences in CF and asthma. Evidence also exists for sex differences with a female advantage in airway diseases which are characterised by flooding of the airways, as in pneumonia and COVID-19, where females have better lung function and lower risk of death than males. The female sex hormone estrogen plays an important role in determining the role of sex biology in airway disease severity and mortality. Estrogen can control the movement of salt and water in and out of the lung airway tubes and dehydrate the lung surface to make it more sticky with mucus, as observed in CF and asthma, thus worsening the condition. In contrast, estrogen can have beneficial effects in lowering the volume of water in the lungs in COVID-19 thus alleviating flooding of the airways. This review focusses on the biology of sex differences in CF, asthma and COVID-19, and the cellular mechanisms by which estrogen can have either detrimental or beneficial effects in these diseases.

Exosome Therapy: A Novel Approach for Enhancing Estrogen Levels in Perimenopause.

Perimenopause significantly impacts women's health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body's natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms.

Bisphenol S causes excessive estrogen synthesis by activating FSHR and the downstream cAMP/PKA signaling pathway.

Estrogen excess in females has been linked to a diverse array of chronic and acute diseases. Emerging research shows that exposure to estrogen-like compounds such as bisphenol S leads to increases in 17ß-estradiol levels, but the mechanism of action is unclear. The aim of this study was to reveal the underlying signaling pathway-mediated mechanisms, target site and target molecule of action of bisphenol S causing excessive estrogen synthesis. Human ovarian granulosa cells SVOG were exposed to bisphenol S at environmentally relevant concentrations (1 µg/L, 10 µg/L, and 100 µg/L) for 48 h. The results confirms that bisphenol S accumulates mainly on the cell membrane, binds to follicle stimulating hormone receptor (FSHR) located on the cell membrane, and subsequently activates the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, leading to enhanced conversion of testosterone to 17ß-estradiol. This study deepens our knowledge of the mechanisms of environmental factors in pathogenesis of hyperestrogenism.

Estrogen deprivation and estrogen receptor α antagonism decrease DSS colitis in female mice.

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium-induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200-fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo-oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.

Effects of different anesthesia methods on labor process and postpartum serum estrogen and progesterone levels in primiparas with painless labor.

OBJECTIVE: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor. METHODS: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods. RESULTS: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05). CONCLUSION: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone.