Reproductive Sciences最新文献

Objective: This study aims to investigate the genetic associations of endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), identify potential key genes using multiple genomic analysis approaches, and analyze their roles in cancer development.

Methods: We integrated large-scale genome-wide association study (GWAS) data from Jiang L et al. and Zhou W et al., combined with blood eQTL data. We employed S-PrediXcan, SMR, and mBAT-combo to assess gene associations with EC, OC, and CC. Additionally, RNA sequencing data were used to analyze the expression levels of key genes across different tissues, followed by functional enrichment analysis to explore their potential biological functions. Results: Through S-PrediXcan, SMR, and mBAT-combo analyses, we identified 690, 620, and 624 genes associated with OC, CC, and EC, respectively. Among them, 79, 59, and 61 genes were consistently significant across all three methods, suggesting their crucial roles in cancer development. Furthermore, we identified multiple comorbidity-related genes, including SPX, which exhibited a negative association with OC, CC, and EC. Transcriptomic analysis revealed that 26 key genes displayed significant expression differences between tumor and normal tissues. Functional enrichment analysis further identified the molecular pathways potentially involved. Conclusion: This study identified a set of key genes associated with EC, OC, and CC and suggested that SPX may play a protective role in cancer development. The integration of multilevel genetic and transcriptomic analyses provides new insights into the molecular mechanisms underlying gynecological malignancies and offers potential biomarkers for future precision medicine research.

Progesterone resistance is a key factor in the failure of conservative treatment in young endometrial cancer patients, and there is no effective method to predict and reverse progesterone resistance. CTMP is known to be involved in the development and progression of endometrial cancer, but the mechanism is unidentified. In this study, the immunohistochemical method was used to detect the expression of CTMP in the endometrium before and after progesterone treatment. In cell culture experiments, cell growth and proliferation were examined using CCK-8 and EDU incorporation assay. CTMP and PI3K/AKT pathway-related proteins expression were examined using Western blot. The results show that CTMP expression in the progesterone-resistant group of AEH was not significantly different from that in the progestin-sensitive group before treatment. There was no significant change in the expression of CTMP in the AEH progestin-resistant group, whereas there was a significant decrease in the expression of CTMP in the progesterone-sensitive group after treatment. CTMP knockdown enhances the sensitivity of endometrial cancer cells to medroxyprogesterone acetate (MPA) and may act by inhibiting the PI3K/AKT signaling pathway. This study confirms that CTMP may be associated with sensitivity to progestin therapy in endometrial atypical hyperplasia and endometrial cancer. CTMP may induce the development of progesterone resistance in endometrial cancer through activation of the PI3K/AKT signaling pathway.

Ovarian tissue vitrification is a key strategy for fertility preservation, but remains hindered by oxidative damage and compromised tissue viability. This study evaluates the cytoprotective effects of glutathione (GSH) supplementation during the vitrification of mouse ovarian tissue, including autologous transplantation experiments. Mice ovaries were cryopreserved with 0, 2, 4, or 8 mM GSH, followed by comprehensive histological, biochemical, and molecular assessments, as well as autologous transplantation to assess functional recovery. GSH, particularly at 4 mM, significantly preserved follicular architecture, enhanced antioxidant enzyme activity, attenuated mitochondrial dysfunction, DNA damage, and apoptosis, and suppressed pro-inflammatory and fibrotic signaling pathways. GSH also restored angiogenic markers and improved endocrine function in ovarian grafts after autologous transplantation, as evidenced by ameliorative levels of estradiol, progesterone, anti-Müllerian hormone (AMH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). These findings support GSH as a potent adjuvant for improving ovarian tissue vitrification outcomes and warrant further translational evaluation in fertility preservation protocols.

Purpose: This study aimed to evaluate the effect of platelet-rich plasma (PRP) on sperm motility in men with asthenozoospermia and assess its potential use in intrauterine insemination (IUI).

Materials and methods: A prospective randomized controlled pilot study was conducted with 40 men diagnosed with asthenozoospermia. Semen samples were divided into two equal parts: one treated with autologous, non-activated PRP and the other serving as control. Sperm motility was assessed at 1, 3, 6, and 24 h using a Makler chamber. A two-step centrifugation method was used for PRP preparation, and all samples underwent identical swim-up protocols. Data were analyzed using two-way repeated measures ANOVA.

Results: PRP-treated samples showed significantly higher motility than controls at all time points (p < 0.001). PRP also slowed the decline in motility over time. At 24 h, motility was 50.5% in the PRP group versus 21.1% in controls. Statistical analysis confirmed normal data distribution.

Conclusion: PRP significantly enhances and preserves sperm motility during in vitro incubation. These findings suggest that PRP may serve as a supportive option in sperm preparation for IUI, potentially reducing the need for more invasive techniques. Further studies are warranted to evaluate clinical outcomes.

Embryonic developmental arrest is a critical factor affecting the success rate of in vitro fertilization and embryo transfer (IVF-ET), and protein arginine methyltransferase 5 (PRMT5) plays a crucial role in early embryonic development. However, the mechanisms by which PRMT5 regulates embryonic development remain largely unexplored. Following the acquisition of informed consent from the patients, human embryos discarded from the IVF process were collected as experimental material. Real-time quantitative polymerase chain reaction (qRT-PCR) and confocal analysis were employed to quantify the levels of PRMT5 mRNA and protein at different developmental stages of early embryos, as well as to assess changes in H4R3me2s methylation levels. Furthermore, PRMT5 knockdown was performed in developmentally arrested embryos to observe its impact on further embryonic development. The results demonstrated a significant increase in both PRMT5 mRNA and protein levels in arrested embryos compared to control embryos. Additionally, a significant increase in the methylation level of H4R3me2s was observed in arrested embryos. The knockdown of PRMT5 has the potential to rescue some of the developmentally arrested embryos. In conclusion, the results of this study indicate that overexpression of PRMT5 leads to developmental arrest in early embryos, which can be partially rescued by knocking down the PRMT5 protein.

Obesity is associated with low fertility potential. Ca2 + oscillations are known to be triggered after sperm oocyte membrane fusion, which allows entry of a sperm-specific phospholipase C-zeta (PLCζ), into the oocyte cytoplasm. We aimed to examine sperm PLCζ expression changes in obese and non-obese men along with sperm parameters. The demographic characteristics of the patients were analysed. The patients included in the study were divided into two groups:Non-obese patients (BMI < 30)(Control)(n:49) and the Obese Patient Group (BMI ≥ 30)n = 18). Semen analysis of the groups was evaluated. Rt-PCR analysis and histopathologic evaluation by immunohistochemistry for PLCζ expression were performed. Testosterone levels in the control group were statistically higher than in the obese group (4.8 ± 1.28 μg/L;3.6 ± 1.61 μg/L, respectively) (p < 0.05). Prolactin levels were 12.6 ± 7.2 μg/L in the control group and 17.15 ± 9.28 μg/L in the obese group, which was statistically significant (p = 0.03). No significant difference was detected between the groups in sperm concentration, motility, morphology, or viability, although semen pH was significantly higher in obese patients (p = 0.024).. Although no statistically significant was observed, PCR analysis revealed that PLCζ expression was elevated by a factor of 1.69 in obese patients. Immunohistochemical staining results showed that PLCζ expression was decreased in obese patients compared to the control group. Although PLCζ mRNA expression was higher in the obese group compared to the control group, immunohistochemical staining results demonstrated weak staining of sperm cells in the obese group. These results indicated that PLCζ protein synthesis pauses at some point in obese patients. The discrepancy between mRNA expression and protein localization may indicate translational or post-translational regulation, though this was not directly assessed in our study. This study highlights the complex relationship between obesity and male fertility, suggesting that obesity may disrupt the translation of PLCζ protein, which is crucial for successful fertilization.

In the quest to enhance food production and quality of life, a variety of chemical agents that can protect crops and prevent vector borne diseases have emerged and are used indiscriminately by humans. Thus, they end up in the physiological systems through various routes. The male reproductive system is one of the highly sensitive physiological systems, despite having the blood-testis and blood-epididymis barrier. In this review, we provide a comprehensive analyses by systematically identifying specific studies that reported the relationship between endocrine disruptors and their toxicity on the male reproductive system at multiple levels. The toxicological aspects of pesticides (organophosphates, organochlorines, carbamates, pyrethroids and neonicotinoids), alkyl phenols, plasticizers, fungicides, herbicides, heavy metals, therapeutic agents, heavy metals, synthetic food preservatives, polycyclic aromatic hydrocarbons and other endocrine disrupting agents on the male reproductive system is detailed, with emphasis on the effects on endocrine signaling, HPG axis and the transgenerational toxicity. We report that endocrine disruptors can cause anatomical pathologies, destruction of specific cell types in the male reproductive organs, decreased spermatogenesis and thereby reduced sperm count, abnormality in the male gametes, altered hormonal production and transgenerational inheritance of the toxic effects.

We primarily investigated the correlation between long-term high-fat diet and male infertility, aiming to reveal the potential mechanisms underlying PCSK9-induced spermatogenic dysfunction in this context. Clinical data revealed that infertile male patients typically exhibited hyperlipidemia and significantly elevated serum PCSK9 concentrations. To further explore this, we utilized wild-type C57BL/6 male mice and their homologous PCSK9-deficient mice, adhering to experimental control principles. After administering a high-fat diet to the experimental groups, we observed local testicular changes. Results indicated that the high-fat diet induced elevated PCSK9 levels in both the serum and testes while decreasing expression of ZO-1, a key protein in blood-testis barrier integrity. PCSK9 knockout effectively improved lipid metabolism in mice fed a high-fat diet and preserved blood-testis barrier integrity. Subsequently, we cultured Sertoli cells (TM4 cells) to explored underlying mechanisms under different treatments. Under high-lipid conditions, we discovered that LOX1-another lipid metabolism regulator was affected by PCSK9. PCSK9 increased LOX1 expression and, in turn, LOX1 increased PCSK9 expression. PCSK9 and LOX1 mutually promoted each other's expression, forming a positive feedback loop that reduced ZO-1 expression. Concurrently, both PCSK9 and LOX1 elevated OxLDL levels and increased TNF-α expression. In summary, the PCSK9-LOX1 feedback loop drives abnormally high OxLDL levels and cellular inflammation, ultimately downregulating the tight junction protein ZO-1 in blood-testis barrier, thereby potentially impairing testicular spermatogenesis.

Hypoxic-ischemic encephalopathy (HIE), which precipitates during parturition, causes severe neurological sequelae in the neonate. We have previously reported an optical monitoring system based on diffuse reflectance spectroscopy to evaluate brain tissue damage that precedes HIE. This study aimed to evaluate the effects of resveratrol on the suppression of HIE development using this monitoring system. After left carotid artery ligation, neonatal rats were intraperitoneally injected with 20 or 40 mg/kg resveratrol and subjected to hypoxic stress. HIE lesions were assessed after 24 h using triphenyl tetrazolium chloride staining. HIE developed in the non-treated group and the group treated with 20 mg/kg administration. Optical parameter assessment during hypoxic stress revealed that HIE-induced brain damage was characterized by a decrease in scatter amplitude, an increase in total hemoglobin in the cerebral blood flow, and a reduction in tissue oxygen saturation. HIE development was completely suppressed in the 40 mg/kg group, in which the changes in the optical parameters were also suppressed. These findings suggest that resveratrol exerts protective effects against HIE by enhancing oxygen supply to the brain. Resveratrol administration could be a promising approach for preventing neonatal HIE.

The efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in couples with unexplained recurrent pregnancy loss (uRPL) may vary according to the number of good-quality blastocysts available. This study is to determine whether PGT-A could improve the cumulative live birth rate (CLBR) among couples experiencing uRPL as the number of high-quality blastocysts increases. A retrospective study involving 1073 couples with uRPL was conducted at a university-affiliated reproductive center. Patients were divided into two groups: 813 participants who underwent PGT-A and 260 participants who underwent conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). A stratified analysis was conducted, which categorized the female participants into three subgroups based on the number of high-quality blastocysts: 1-3, 4-6, and ≥ 7. A binary logistic regression model was used to evaluate the associations between the number of high-quality blastocysts and the cumulative pregnancy outcomes. Among uRPL patients undergoing PGT-A or IVF/ICSI, there were respectively 421 vs. 129 with 1-3 blastocysts, 252 vs. 69 with 4-6 blastocysts, and 140 vs. 62 with ≥ 7 blastocysts. In 1-3 blastocysts subgroup, CLBR was 23.52% after PGT-A vs. 33.33% after IVF/ICSI (adjusted OR 1.005, 95% CI 0.604-1.674, p = 0.984). In 4-6 blastocysts subgroup, CLBR was 53.17% after PGT-A vs. 75.36% after IVF/ICSI (adjusted OR 0.398, 95% CI 0.197-0.802, p = 0.010). In ≥ 7 blastocysts subgroup, CLBR was 73.57% after PGT-A vs. 66.13% after IVF/ICSI (adjusted OR 1.660, 95% CI 0.729-3.799, p = 0.227). In these three subgroups, clinical pregnancy loss rates were all similar between the two treatment methods. In women with uRPL, PGT-A did not improve CLBR, irrespective of the number of high-quality blastocysts available. Routine use of PGT-A in this population is therefore not recommended. Future high-quality randomized controlled trials may better define its appropriate indications.