Reproductive Sciences最新文献

The extracellular matrix (ECM) critically influences cell behavior, yet its properties in human endometrial lesions (HEL) and human uterine fibromas (HUF) are not well characterized. This study aimed to characterize their ECM and evaluate its impact on cell engraftment and proliferation while optimizing a decellularization protocol. HEL and HUF tissues, collected during laparoscopic surgeries, were decellularized using a novel protocol. Complete cell removal and preserved ECM microstructure were confirmed by histology, DAPI, Masson's trichrome staining and scanning electron microscopy. The decellularized scaffolds were used as a platform for three-dimensional culture of human endometrial-derived mesenchymal stem cells (hEMSCs), with HUF serving as a fibrotic control originated from the same organ system. The biological impact of the ECM was assessed via immunohistochemistry for engraftment marker matrix metalloproteinase-9 and proliferation marker antigen Kiel-67. The in vivo recellularization potential of HEL scaffolds was further evaluated in a rat model, with HEL scaffold group at two timepoints (n = 6/group) and a sham control (n = 3). Results confirmed complete decellularization with maintained ECM integrity in both HEL and HUF. In vitro evaluation indicated that hEMSCs seeded more efficiently onto HEL scaffolds (51.16 ± 28.84) compared to HUF scaffolds (6.16 ± 7.29) (p = 0.012). The in vivo peritoneal implanted HEL scaffolds demonstrated significant time-dependent host cell recruitment and remodeling compared to the sham control. In conclusion, the decellularized HEL scaffold provides a superior ECM platform for cell seeding and engraftment compared to HUF, making it a promising platform for modeling endometriosis in both in vitro and in vivo settings.

E2F family transcription factors are involved in various cancers, yet the role of E2F transcription factor 8 (E2F8) in endometrial cancer (EC) remains elusive. This study explores how E2F8 transcriptionally activates denticleless E3 ubiquitin protein ligase homolog (DTL) to promote EC progression via the MAPK signaling. Bioinformatic analysis of the GEO dataset GSE63678, along with GEPIA2, AnimalTFDB v4, and ChIP-Atlas, identified E2F8 and its potential target DTL in EC. Elevated expression of E2F8 and DTL was confirmed in EC tissues, which correlated with a higher International Federation of Gynecology and Obstetrics stage. Functional assays demonstrated that E2F8 knockdown suppressed EC cell proliferation, migration, invasion, and MAPK pathway activation, while DTL overexpression or PDCD4 knockdown reversed these effects. Knockdown of DTL enhanced PDCD4 ubiquitination. In vivo, silencing of E2F8 inhibited tumor growth in EC xenograft models, whereas DTL upregulation or PDCD4 knockdown restored tumor progression and enhanced MAPK pathway activity and Ki67 expression. In conclusion, E2F8 promotes EC progression by transcriptionally activating DTL and activating the MAPK pathway. These findings provide novel mechanistic insights into EC progression and suggest that the E2F8/DTL/PDCD4/MAPK axis may serve as a potential therapeutic target for EC.

In the intricate landscape of health disorders in women, polycystic ovary syndrome and endometriosis stand out. Despite their complete etiology being unknown, their impact on women's health and link to hereditary factors have given them the spotlight in the world of gynaecology and endocrinology. These two conditions although vastly different, share common symptoms, clinical manifestations, pathways and genetic and epigenetic factors and regulators [10, 39]. Decoding the link between the two conditions can lead to enormous breakthroughs in the diagnostic and therapeutic aspects of gynaecological disorders and possibly aid in the unravelling of unknown mechanisms associated with the pathophysiology of PCOS and endometriosis. MicroRNAs being small and potent regulators of gene expression, are infamous for their role in regulation of mRNA expression and aiding in post transcriptional modifications and their association with gynaecological disorders and impact on the endocrine system, typically the Hypothalamic-Pituitary-Ovarian axis has garnered an enormous amount of attention. MicroRNAs are known to affect pathways linked to inflammation, immunity, neuroendocrine stress response, fertility, metabolism, environmental response and are actively associated with the clinical manifestations of a plethora of diseases and disorders [37, 49-51]. This comprehensive review showcases the multifaceted roles of microRNAs involved in gynaecological disorders, specifically PCOS and endometriosis, offering avenues for microRNAs as possible therapeutic and diagnostic markers in gynaecological disorders, harnessing their applications to the maximum extent, possibly aiding in betterment of overall health in women.

Endometriosis (EMS) is a non-cancerous invasive condition where tissue resembling the lining of the uterus is found outside of the uterine cavity. Endometriotic lesions have been found in nearly every organ of the body. This review highlights examples of EMS exhibiting all eight established hallmarks of cancer: hyperproliferation (e.g. through estrogen signalling), evasion of growth suppression (e.g. through progesterone resistance), immunosurveillance evasion (e.g. through reduction of natural killer cell cytotoxicity), enabling replicative immortality (e.g. through increased telomere length), invasion (e.g. through epithelial-to-mesenchymal transition), induction of angiogenesis (e.g. through upregulation of hypoxia-inducible factors), resistance to apoptosis (e.g. through increased expression of survivin), and deregulation of cellular metabolism (e.g. through increased production of lactate). Therefore, despite being considered a non-cancerous, benign condition, EMS is highly cancer-like in its behaviours to promote invasion and ectopic survival. The presence of all hallmarks of cancer amongst endometriotic behaviours highlights that to expand understanding of endometriotic metastasis, as well as potential modes for management of EMS, it may be possible to leverage the larger knowledge base associated with cancer.

Our study aimed to investigate the association between chronic endometritis (CE) and thyroid peroxidase antibody (TPOAb) positivity, and to evaluate the effect of antibiotic therapy on assisted reproductive technology (ART) outcomes in patients with TPOAb-positive CE. A total of 1,385 women undergoing ART were enrolled and categorized into TPOAb-negative (n = 1,240) and TPOAb-positive (n = 145) groups. The prevalence of CE was significantly higher in the TPOAb-positive group compared with the TPOAb-negative group (62.76% vs. 43.47%, p < 0.001). At our center, patients diagnosed with CE routinely received antibiotic therapy prior to ART. In subgroup analyses restricted to CE patients, with clinical pregnancy rate (CPR) and live birth rate (LBR) as the primary outcomes, TPOAb-positive patients with CE who received antibiotics showed significantly higher CPR (52.75% vs. 41.37%, p = 0.0426) and LBR (48.35% vs. 35.44%, p = 0.0184). These associations remained robust after adjustment for potential confounders. In conclusion, TPOAb positivity is linked to a higher prevalence of CE, and antibiotic therapy prior to ART improves reproductive outcomes in TPOAb-positive patients with CE.

Nesfatin-1 is a peptide hormone that is commonly associated with appetite regulation and is primarily expressed in the brain. However, it has recently been identified in various peripheral organs, including the ovaries and uterus. This study aimed to investigate the expression and functional role of nesfatin-1 in the mouse endometrium. Due to the lack of established mouse endometrial cell lines, a primary culture system was developed by isolating endometrial cells through enzymatic digestion, enabling in vitro analyses. We examined the presence and regulatory potential of nesfatin-1 in these cells, focusing particularly on endometrial decidualization, a critical process for implantation and pregnancy maintenance. Our results revealed that nesfatin-1 and its binding sites are expressed in mouse endometrial cells. Furthermore, Nucb2 mRNA expression was significantly increased following estradiol treatment but not progesterone treatment, suggesting hormone-specific regulation of nesfatin-1 expression. Notably, nesfatin-1 treatment to mouse endometrial cells resulted in a significant upregulation of decidualization-associated genes, including prolactin family 8, subfamily a, member 2 (Prl8a2), alkaline phosphatase (Alpl), and bone morphogenetic protein 2 (Bmp2). Furthermore, in a delayed implantation mice model, there was a significant decrease in Nucb2/nesfatin-1 expression and decidualization-associated genes. Importantly, nesfatin-1 administration restored the expression of these genes in the delayed implantation conditions. Taken together, these findings demonstrate that nesfatin-1 plays a pivotal role in promoting endometrial decidualization and successful implantation, suggesting its potential as a therapeutic target for enhancing fertility and improving pregnancy outcomes.