Reproductive Sciences最新文献

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.

This study explores the molecular mechanisms driving recurrent spontaneous abortion, a condition affecting 1-5% of women of reproductive age, with 40-50% of cases unexplained. Focusing on endometrial cell senescence, a process linked to irreversible cell cycle arrest, the research identifies uncoupling protein 2 (UCP2) and glutathione reductase (GSR) as key contributors to this pathology. By analyzing transcriptome data from the Gene Expression Omnibus database, 21 genes associated with cellular senescence were found to be differentially expressed, with UCP2 and GSR significantly upregulated. These findings were validated using a hydrogen peroxide-induced senescence model in human endometrial stromal cells. Diagnostic potential was confirmed through receiver operating characteristic curve analysis, showing promising results for both UCP2 and GSR. The study also observed increased activity of natural killer and T cells in affected tissues, pointing to an immune component in recurrent spontaneous abortion. Drug prediction analysis highlighted dexamethasone and menadione as potential treatments. These insights suggest that oxidative stress-induced senescence plays a critical role in recurrent spontaneous abortion, with UCP2 and GSR as promising biomarkers and therapeutic targets to improve endometrial health and reduce miscarriage risk. Further clinical studies are needed to validate these findings and explore their therapeutic applications.

Varicocele, a condition of insufficient oxygen supply to testicular tissue leading to hypoxia, is a major factor contributing to male infertility. This study investigated the potential protective effects of N-acetylcysteine (NAC), a potent antioxidant, on sperm characteristics and hormonal receptor expression in a rat model of varicocele-induced testicular injury. Thirty-two adults male Wistar rats were randomly assigned to four groups: Sham, varicocele, varicocele with NAC treatment (varicocele + NAC), and NAC treatment only (NAC). Serum testosterone, LH, and FSH levels were measured, and sperm characteristics, testicular histology, and expression of some genes involved in sperm motility (Catsper-1 and Catsper-2), germ cell development (FSHR), and steroidogenesis (SF-1 and LHCGR) were evaluated in each group. Results revealed that varicocele significantly decreased serum testosterone levels, while simultaneously decreasing sperm quality, germ cell count, and expression of all the mentioned genes (P < 0.05). Also, the level of LH and FSH was significantly increased (P < 0.05). Notably, NAC treatment significantly improved sperm quality and protected testicular tissue against varicocele, suggesting its potential as a therapeutic agent for male infertility. This study demonstrates that NAC may offer a promising strategy for mitigating testicular damage induced by Varicocele.

Melatonin is multifaceted neurohormone secreted by pineal gland during darkness which is regulated by a small region present in hypothalamus i.e. Suprachiasmatic nucleus (SCN). Although melatonin primarily regulates the sleep and wake cycles, its effects are not limited to sleep. It also contributes to a number of physiological processes, including hormone regulation, metabolism, reproduction and body temperature regulation. Research has consistently highlighted the potential of melatonin to support reproductive health by enhancing testosterone synthesis, promoting gametogenesis, and improving both sperm quality and motility. Moreover, it has been found that melatonin improves fertilization rate and oocyte quality, making it a valuable adjunct in fertility treatments for both men and women. Beyond its role in reproductive function, melatonin also possesses potent anti-apoptotic, antioxidant, anti-inflammatory and properties. These effects help safeguard reproductive cells from the harmful impacts of oxidative stress and DNA damage, further underscoring melatonin's importance in maintaining optimal fertility and overall reproductive health. Despite its potential benefits, melatonin utility in reproductive health remains controversial due to inconclusive evidence, unclear mechanism and scattered information. Additionally, the supplementation of dosage and duration of melatonin in infertility and reproductive health needs exploration. In this review, we have tried to summarize the findings from various clinical and pre-clinical studies demonstrating the therapeutic potential of melatonin in male and female fertility and reproductive health. Aim of this review is to provide a deep knowledge on the current status of melatonin's potential therapeutic effects on reproductive health with emphasis on the molecular mechanism and future directions in melatonin's utility in reproductive health.

Objective: This study aimed to assess the diagnostic and prognostic value of four biochemical markers-PAX9, HK10, TBX2, and CYFRA21-1-in ovarian carcinoma (OC).

Methods: We conducted a prospective diagnostic study from December 2020 to December 2021, enrolling 88 patients with ovarian carcinoma, 90 with benign ovarian lesions, and 92 healthy controls. Blood levels of HK10 and CYFRA21-1 were measured, while tissue expressions of PAX9 and TBX2 were analyzed. We used logistic regression and ROC curve analysis to evaluate the diagnostic performance of these markers.

Results: The OC group showed significantly higher positive expression rates of PAX9 and TBX2 compared to the benign group (65.91% vs. 4.44% and 26.14% vs. 3.33%, respectively). Additionally, HK10 and CYFRA21-1 levels were significantly elevated in the OC group compared to both the benign and healthy groups (P < 0.05). The expressions of all four markers were closely associated with clinical parameters such as tumor diameter, FIGO stage, degree of differentiation, and lymph node metastasis (P < 0.05). The sensitivity and specificity value of CA125, HK10, CYFRA21-1, PAX9, and TBX2 in the diagnosis of ovarian cancer were 85.09% and 80.09%, 65.87% and 61.67%, 81.25% and 79.59%, 75.32% and 74.49%, and 61.46% and 69.39%, respectively. The sensitivity and specificity of the combined biomarkers diagnosis are respectively 87.59% and 84.69%.

Conclusion: The combined assessment of PAX9, HK10, TBX2, and CYFRA21-1 provides significant diagnostic and prognostic value in ovarian carcinoma, with HK10 showing particularly high sensitivity. These markers could play a crucial role in the early detection and management of ovarian carcinoma.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine and metabolic condition that affects around 8-13% of women worldwide. PCOS is defined by hyperandrogenism, insulin resistance, and many reproductive irregularities, providing significant challenges with diagnosis and treatment. Here thoroughly analyzes the many animal models used to conduct PCOS research, focusing on their mechanisms, benefits, and drawbacks. Multiple models, including those influenced by androgens (testosterone and DHEA), estrogen, aromatase inhibitors (such as letrozole), and progesterone receptor antagonists (like RU486), are examined for their capacity to recreate the clinical characteristics of PCOS. Although animal models are frequently employed for their cost-efficiency and simple handling, they provide difficulties in correctly replicating human physiology due to variations in reproductive biology. The research highlights the importance of advanced animal models that represent the complete range of PCOS symptoms seen in humans. Furthermore, it emphasizes the significance of these models in understanding the pathophysiology of PCOS and in developing beneficial therapeutic approaches. Future research must concentrate on improving current models and investigating novel approaches for a more accurate depiction of this complex disease to optimize translational results in clinical conditions.

Endometriosis is a prevalent chronic inflammatory condition impacting 5-10% of reproductive-age women, commonly resulting in debilitating pelvic pain and infertility. Despite extensive research efforts, the precise underlying pathophysiology remains largely unclear. Emerging evidence increasingly suggests that cellular senescence, iron overload, and fibrosis collectively form a critical pathological axis that significantly contributes to the persistence and severity of the disease. However, the intricate mechanistic interplay between the immune system's failure to effectively clear senescent cells, the damaging effects of iron-induced oxidative stress, and the subsequent fibrotic remodelling is still poorly understood. This narrative review highlights the interconnected roles of impaired immune clearance of senescent cells, iron accumulation, and fibrosis development in driving endometriosis pathogenesis. The review aims to clarify how iron overload and cellular senescence contribute to the progression of endometriosis. It also evaluates novel therapeutic strategies that target iron dysregulation and senescence pathways. By exploring this detrimental triad, we seek to identify potential new avenues for transforming the management of endometriosis, offering hope for more effective treatments to alleviate the significant burden on affected women.