Explore the vast range of titles available.

Infertility caused by ovarian or tubal problems can be treated using In Vitro Fertilization and Embryo Transfer (IVF-ET); however, this is not possible for women with uterine loss and malformations that require uterine reconstruction for the treatment of their infertility. In this study, we are the first to report the usefulness of decellularized matrices as a scaffold for uterine reconstruction. Uterine tissues were extracted from Sprague Dawley (SD) rats and decellularized using either sodium dodecyl sulfate (SDS) or high hydrostatic pressure (HHP) at optimized conditions. Histological staining and quantitative analysis showed that both SDS and HHP methods effectively removed cells from the tissues with, specifically, a significant reduction of DNA contents for HHP constructs. HHP constructs highly retained the collagen content, the main component of extracellular matrices in uterine tissue, compared to SDS constructs and had similar content levels of collagen to the native tissue. The mechanical strength of the HHP constructs was similar to that of the native tissue, while that of the SDS constructs was significantly elevated. Transmission electron microscopy (TEM) revealed no apparent denaturation of collagen fibers in the HHP constructs compared to the SDS constructs. Transplantation of the decellularized tissues into rat uteri revealed the successful regeneration of the uterine tissues with a 3-layer structure 30 days after the transplantation. Moreover, a lot of epithelial gland tissue and Ki67 positive cells were detected. Immunohistochemical analyses showed that the regenerated tissues have a normal response to ovarian hormone for pregnancy. The subsequent pregnancy test after 30 days transplantation revealed successful pregnancy for both the SDS and HHP groups. These findings indicate that the decellularized matrix from the uterine tissue can be a potential scaffold for uterine regeneration.

Background A balance between estrogen (E2) and progesterone (P4) is vital for a successful pregnancy, and an imbalance between these two hormones yields female infertility. E2 mediates uterine receptivity and regulates endometrial growth, the immune system, and hormone signaling by rapidly inducing early growth response 1 (EGR1). However, the precise mechanism by which EGR1 regulates E2-mediated uterine growth remains unclear. This study examined the transcriptional signatures of ovariectomized (OVX) Egr1 knockout (KO) mice compared to those of wild-type (WT) mice to clarify the function of EGR1 in the E2-dependent uterine response. Results Egr1 KO uteri exhibited an impaired E2 response, with significant changes in the expression of the key genes Bgn , c-Kit , Ripor2 , and Arg2 . During early E2 response, Egr1 KO uteri showed upregulated insulin-like growth factor (IGF) signaling pathway genes and downregulated reproduction-related genes. During late E2 response, Egr1 KO uteri showed enhanced proliferative processes, such as DNA replication and mitotic cell cycle phase transition, potentially related to poly-ADP ribosylation (PARylation), along with a reduction in immune response. Notably, the transcriptional signatures in mature OVX Egr1 KO uteri resembled those in immature uteri, with similar increases in proliferation and decreases in immune response at the pathway level. Conclusions Our findings indicate that EGR1 is essential for regulating immune response and uterine proliferation via IGF signaling and PARylation, and acts as a gatekeeper transcription factor that mediates E2 actions in the mature uterus. Notably, we found that the transcriptional signatures of EGR1 in mature uteri overlapped with the primary E2 function and suggested a novel concept that these transcriptional signatures in mature Egr1 KO uteri are similar to those of immature uteri. Our findings offer novel insights into the role of EGR1 as an E2 mediator in the uterus at the molecular level.

Endometritis is one of the important causes of infertility. Puerarin (PU) can inhibit oxidative stress and reduce inflammation; however, it is unclear whether PU has a protective effect on the endometritis. In our study, we used Staphylococcus aureus to induce mouse endometritis. The PU group (100 mg/kg PU) and the S. aureus + PU group received daily intraperitoneal injection of PU (25, 50 or 100 mg/kg PU). The results showed that S. aureus significantly increased the levels of MPO, TNF‐α, IL‐1β and IL‐6 in uterine tissue, and increased the expression of p‐p65 and p‐IκBα proteins in uterine tissue to induce endometritis in mice (p < 0.05). Furthermore, it has been found that S. aureus promotes the occurrence of ferroptosis by reducing GSH and ATP content, increasing MDA and iron content and reducing GPX4 and SLC7A11 protein expression levels (p < 0.05). S. aureus significantly increase the expression of NLRP3, ASC, caspase‐1 and P2X7 proteins in uterine tissue (p < 0.05). However, PU obviously reduced the inflammatory response and reversed the changes of ferroptosis and the expression of P2X7 receptor/NLRP3 pathway associated proteins of the uterus induced by S. aureus (p < 0.05). Taken together, these findings emphasize the protective effect of PU on endometritis by regulating the P2X7 receptor/NLRP3 signalling pathway and inhibiting ferroptosis.

Context: Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions.Objective: The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model.Materials and methods: PCOS was induced in Sprague–Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied.Results: Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p < 0.05), percentage diestrous phase (p < 0.001), testosterone (p < 0.001), 3β-HSD (p < 0.01) and 17β-HSD (p < 0.001) enzyme activity and oxidative stress. Histological results reveal that soy isoflavones treatment in PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary.Discussion: Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood.Conclusion: Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

Endocrine-active compounds (EACs) derived from anthropogenic activities and bioactive components in maternal milk influence neonatal development, a critical period for postnatal uterine morphogenesis. Here, using an ex vivo model, we investigated whether neonatal exposure to the antiandrogen 2-hydroxyflutamide, the environmental estrogen 4- tert -octylphenol, and the organochlorine insecticide metabolite HPTE (which exhibits estrogenic, antiestrogenic, and/or antiandrogenic activity) induces oxidative stress and alters proliferation and apoptosis in uterine explants from 10-day-old piglets. Additionally, we assessed whether natural feeding provides protection against the adverse effects of EACs. We found that EACs disrupting androgen or estrogen signaling increased ROS/RNS production, enhanced specific antioxidant enzyme activity, and/or induced apoptosis exclusively in sow-fed piglets, suggesting a compensatory mechanism to maintain cellular homeostasis. Its absence in formula-fed piglets may indicate a reduced capacity to activate protective mechanisms against EACs, potentially due to delayed development. In contrast, EAC-induced alterations in uterine cell proliferation occurred in both feeding groups in a cell type- and feeding-dependent manner. These findings suggest that natural feeding does not fully protect against EAC-induced uterine development disruption, which may have long-term reproductive consequences. Moreover, they reinforce the notion that the neonatal period is a critical window of uterine development, highly sensitive to endocrine disruptors.

Menopause is a natural biological aging process characterized by the loss of ovarian follicular function and decrease estrogen levels. These hormonal fluctuations are associated with increased iron levels, which ultimately lead to iron accumulation. This study aims to investigate the effects of Deferasirox on iron homeostasis and hematopoiesis in ovariectomized rats with iron accumulation. Sixty-four female Wistar rats were divided into eight groups and underwent ovariectomy surgery to simulate menopause. Iron accumulation was induced through the injection of ammonium ferric citrate. Deferasirox was administered at doses of 50 mg/kg and 100 mg/kg. Hematological parameters, iron profile, antioxidant markers, oxidative stress indicators, histopathological evaluation of uterine, bone, bone marrow, liver, and spleen tissues, flow cytometric analysis of hematopoietic CD markers, and relative expression of Hamp, Pu.1, Gata1, and Gdf11 genes were analyzed. Deferasirox treatment improved histopathological changes in the uterine tissue of ovariectomized rats with iron accumulation, increased the number of white blood cells, and reduced serum iron levels, TIBC, ferritin, and transferrin saturation percentage. It also increased serum antioxidant capacity and reduced oxidative stress markers. Deferasirox had a positive effect on femur bone, hematopoietic cell count, volume of hematopoietic and adipose tissues in bone marrow, extramedullary hematopoiesis in the liver and spleen, and influenced the relative expression of Hamp, Pu.1, Gata1, and Gdf11 genes related to hematopoiesis and iron metabolism. In conclusion, Deferasirox effectively manages iron homeostasis and hematopoiesis in ovariectomized rats with iron accumulation and suppresses oxidative stress.

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial–mesenchymal transition in IUA models.

Aspirin has been shown to enhance endometrial receptivity (ER) during the window of implantation in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms by which aspirin improves ER through metabolic analysis of uterine lavage fluid. A PCOS rat model was established using letrozole. Body weight and estrous cycles were monitored, and the number of implanted embryos was assessed across groups. We evaluated endometrial ultrastructure, ovarian and endometrial histomorphometry. Serum levels of estradiol(E2) and progesterone(P)were measured. Moreover, through ultra-performance liquid chromatography-mass spectrometry, the study of uterine lavage fluid metabolites revealed the potential mechanism of action of aspirin. Compared with the model group, aspirin treatment significantly increased embryo implantation rates, improved endometrial morphology and hormone levels. Metabolomic analysis identified 48 differential metabolites, among which five-2, 6-dihydroxypurine, gluconolactone, Oxaceprol, PC (18:1/18:1), and PC (20:3e/17:1)-were identified as potential biomarkers for aspirin-mediated improvement of ER in PCOS rats. Pathway analysis revealed that aspirin primarily modulates the pentose phosphate pathway, arginine and proline metabolism, and glycerophospholipid metabolism. Aspirin may enhance glucose metabolism, alleviate insulin resistance, promote angiogenesis, and improve vascular permeability and endometrial receptivity. These effects are likely mediated through the regulation of biomarkers involved in the pentose phosphate pathway, arginine and proline metabolism, and glycerophospholipid pathways in uterine lavage fluid.

17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF2°). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF2° to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF2° mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF2° in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF2° LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect.

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been shown to interfere with the endocrine system, leading to adverse effects on reproductive health. In females, EDC exposure has been linked to menstrual irregularities, infertility, and pregnancy complications. Epigenetic regulation, which involves modifications to DNA and histones that do not alter the underlying genetic code, plays a crucial role in female reproduction. EDCs have been shown to disrupt epigenetic mechanisms, leading to changes in gene expression that can have long-term effects on reproductive outcomes. Several EDCs, including bisphenol A (BPA) and phthalates, dioxins, and polychlorinated biphenyls (PCBs), have been shown to alter DNA methylation patterns and histone modifications in female reproductive tissues. These changes can lead to altered expression of genes involved in ovarian function, implantation, and placental development. Here, we integrate epidemiological and experimental evidence from the last 20 years to profile the types of diseases that EDCs trigger in the female reproductive system in relation to the uterus, and the corresponding molecular mechanisms that have been studied. In addition, this review will outline the state of knowledge of EDC epigenetic regulation in the uterus and how it impacts reproductive health, as well as identify areas for future research.