Reproductive Sciences最新文献

The high-altitude hypoxia model demonstrates that insufficiently oxygenated placentas activate compensatory mechanisms to ensure fetal survival, hinging on the transcription factor hypoxia-inducible factor-1. The aim of the present study is to investigate whether and when similar mechanisms are also activated during intrauterine growth restriction (IUGR). A retrospective observational study evaluated a series of umbilical cord blood samples, which provide a realistic representation of the fetal intrauterine status, collected from a cohort of preterm and term neonates, both affected and not affected by IUGR. Results demonstrate that preterm IUGR fetuses receive a lower supply of oxygen and glucose from the placenta, along with a greater provision of lactate and carbon dioxide compared to non-IUGR neonates. Simultaneously, preterm IUGR fetuses increase oxygen extraction and reduce lactate production. These differences between IUGR and non-IUGR placentas and fetuses disappear as the term of pregnancy approaches. In conclusion, this study suggests that hypoperfused placentas in preterm pregnancies with IUGR activate a metabolic reprogramming aimed at favoring glycolytic metabolism to ensure fetal oxygenation, even though the availability of glucose for the fetus is reduced. Consequently, preterm IUGR fetuses activate gluconeogenetic metabolic reprogramming, despite it being energetically expensive. These metabolic adaptations disappear in the last weeks of pregnancy, likely due to physiological placental aging that increases the fetoplacental availability of oxygen. Placental oxygenation appears to be the main driver of metabolic reprogramming; however, further studies are necessary to identify the underlying biological mechanisms modulated by oxygen.

Preeclampsia (PE), an idiopathic hypertensive disorder that arises during pregnancy, poses a serious threat to the health of expectant mothers. Human chorionic trophoblast cells (HTR-8/SVneo) are associated with the development of PE. It has been reported that circ_0008440 expression is abnormally increased in the placental tissues of PE patients. However, the function of circ_0008440 within HTR-8/SVneo cells during PE has yet to be fully elucidated. The study used RT-qPCR and western blot assay to evaluate the expression levels of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 2 (PFKFB2), circ_0008440, and miR-942-5p in PE patients. Cells viability was measured using cell counting kit-8 (CCK-8) assay. Cell cycle assay and 5-ethynyl-2'-deoxyuridine (EDU) assay were used to measure cell proliferation. Cell apoptosis was assessed using flow cytometry assay. Western blot assay was used to detect protein expression. Dual-luciferase reporter assay and RNA pull-down assay were used to assess the interactions among circ_0008440, miR-942-5p, and PFKFB2 in HTR-8/SVneo cells. The study showed that the expression levels of circ_0008440 and PFKFB2 were significantly increased, while the expression of miR-942-5p was significantly decreased in the placental tissues of PE patients. Silencing of circ_0008440 promoted proliferation and tube formation and inhibited apoptosis of HTR-8/SVneo cells. In terms of molecular mechanism, miR-942-5p inhibitor or overexpression of PFKFB2 could partially reverse the effects of circ_0008440 silencing on the biological characteristics of HTR-8/SVneo cells. Collectively, circ_0008440 could act as a sponge of miR-942-5p to regulate the expression of PFKFB2, which further inhibited viability and proliferation of HTR-8/SVneo cells and promoted cell apoptosis.

This study investigates the association between parity and type 2 diabetes mellitus (T2DM) in Japanese women, considering the clinical history of gestational diabetes mellitus (GDM) and menopausal status, which are known risk factors for T2DM. Overall, 30,116 Japanese women (6,588 premenopausal and 23,528 postmenopausal) were included in this cross-sectional study. They were divided into two groups according to menopausal status (premenopausal and postmenopausal women), and the association between parity and T2DM was evaluated using a multiple logistic regression model with possible confounders, including a clinical history of GDM. The association between parity and T2DM was not statistically significant in premenopausal women. In contrast, a linear graded association between parity and T2DM was found in postmenopausal women. Furthermore, the association between parity and T2DM in postmenopausal women was attenuated after adjusting for body weight gain after the age of 20 years. A clinical history of GDM was significantly associated with a high risk for T2DM, regardless of adjustment for body weight gain after the age of 20 years in both premenopausal and postmenopausal women. Parity is associated with an increased risk of T2DM in postmenopausal women but not in premenopausal women. Maintaining appropriate body weight would be beneficial in attenuating the risk of T2DM in postmenopausal women. A clinical history of GDM is a risk factor for T2DM in both pre- and postmenopausal women; therefore, women with a clinical history of GDM require continuous medical care to survey for T2DM.

Circulating miRNAs (C-miRNAs) occuring in a cell-free form within body fluids and other extracellular environments have garnered attention in recent times. They offer deeper insight into various physiological and pathological processes which include reproductive health. This review delves into their diagnostic potential across a spectrum of reproductive disorders, including conditions affecting ovarian function, male infertility and post pregnancy issues. Through analysis of C-miRNA profiles in bodily fluids, researchers uncover crucial markers indicative of reproductive challenges. Dysregulated C-miRNAs emerge as important players in the progression of several reproductive disorders which is the main focus of this review. Advancements in technology, facilitate precise detection and quantification of C-miRNAs, paving the way for innovative diagnostic approaches. Challenges in studying C-miRNAs, such as their low abundance and variability in expression levels, underscore the need for standardized protocols and rigorous validation methods. Despite these challenges, ongoing research endeavors aim to unravel the complex regulatory roles of C-miRNAs in reproductive biology, with potential implications for clinical practice and therapeutic interventions.

Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced. Eight weeks postoperatively, the VCL group exhibited significant testicular damage and sperm abnormalities. Western blot analysis revealed upregulation of ER stress-related proteins and downstream apoptotic markers in the VCL group. For further investigation, we developed an in vitro oxidative stress model using GC-2 cells treated with 400 µM hydrogen peroxide (H₂O₂) for 12 h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H₂O₂ and the ER stress inducer significantly reduced GC-2 cell viability and increased reactive oxygen species (ROS) production, ER stress, and apoptosis. Conversely, treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects. Our findings suggest a strong association between VCL-induced redox imbalance and ER stress-related injury driven by the UPR in this rat model. Furthermore, 4-PBA effectively reduced germ cell damage induced by ROS-mediated ER stress, offering potential therapeutic insights for treating VCL-related infertility.

There is limited clinical research investigating the optimal transplantation strategy in early oocyte retrieval cycles. We aimed to assess whether the maturation of oocytes from early oocyte retrieval influenced pregnancy outcomes, and to find the optimal embryo transfer strategy (fresh or frozen-thawed embryo transfers) for patients who had early oocyte retrieval and underwent in vitro maturation (IVM). A retrospective cohort study was conducted in a university-based reproductive medical center. A total of 234 women who underwent single embryo transfer after early oocyte retrieval were included. The primary outcome was live birth rate. The live birth rate (12.5% vs. 27.5%, p = 0.005, adjusted p = 0.010) was significantly lower in IVM cycles compared with no IVM cycles. There was a significant decrease in live birth (3.6% vs. 19.0%, p = 0.008, adjusted p = 0.011) and a markedly elevated early pregnancy loss rate (62.5% vs. 11.1%, p = 0.014, adjusted p = 0.012) for IVM fresh cycles compared with no IVM fresh cycles. However, these findings were not repeated in subgroup analysis when frozen-thaw embryos were transferred. These results indicate that patients who underwent early oocyte retrieval and then IVM-intracytoplasmic sperm injection should be recommended the embryo cryopreservation strategy. Resynchronization of the embryo and the endometrium in frozen-thaw embryo transfer cycles may optimize live birth and decrease early pregnancy loss in IVM-intracytoplasmic sperm injection cycles after early oocyte retrieval.

Granulocyte colony-stimulating factor (G-CSF), a pivotal hematopoietic cytokine, has been noted for its potential to bolster embryo implantation and augment endometrial receptivity. The present meta-analysis endeavors to evaluate the therapeutic efficacy of G-CSF in mitigating the incidence of recurrent miscarriages, thereby enriching the clinical evidence supporting its use in treatment protocols. Our exhaustive literature search, concluded on August 25, 2024, spanned across various databases including PubMed, Medline, Cochrane Library, Web of Science, ClinicalTrials, China National Knowledge Infrastructure (CNKI), Weipu, and Wanfang, to identify and analyze randomized controlled trials (RCTs) that assessed the impact of G-CSF on recurrent miscarriage. Our review incorporated 7 RCTs. The application of G-CSF was linked to a marked reduction in the rate of miscarriage [RR = 0.48, 95% CI (0.27, 0.86), P = 0.01]. Subgroup analysis indicated that the intra-uterine infusion of G-CSF was notably effective in diminishing the miscarriage rate (RR = 0.35, 95% CI (0.18, 0.68), P = 0.002), while subcutaneous administration did not exhibit a significant impact (RR = 0.55, 95% CI (0.26, 1.20), P = 0.13). Moreover, the administration of G-CSF during the ovulatory phase was identified as particularly efficacious in reducing the miscarriage rate (RR = 0.33, 95% CI (0.18, 0.63), P < 0.001). Intrauterine administration of G-CSF, particularly during the ovulatory phase, is associated with a significant decrease in miscarriage risk and an enhancement in the likelihood of a successful pregnancy outcome in patients with a history of recurrent miscarriages. These findings highlight G-CSF's promise as a valuable therapeutic intervention in this medical scenario.

The decline in sperm parameters among obese males has attracted significant scholarly interest. The intestinal microbiota plays a crucial role in obesity, and investigating the intestinal-reproductive axis may offer a novel molecular approach to addressing the decline in male sperm parameters caused by obesity. To clarify whether probiotics, either alone or in conjunction with metformin, can enhance sperm parameters in obese male mice and assess the underlying mechanisms involved. 6-week-old male mice were constructed as obese models. Probiotics and metformin were used as intervention conditions. Changes in inflammatory factors and ROS content were detected by ELISA, morphological changes in testicular and colon tissues were observed by H&E staining, changes in intestinal microbiota abundance were detected by 16SrRNA gene sequencing, and changes in metabolites such as blood glucose, blood lipids, and lipopolysaccharide were detected by biochemical testing to investigate the mechanism of probiotics, metformin, and their combination to ameliorate reproductive impairment in obese male mice. Our results revealed that high-fat diet would result in reduced testicular spermatogenic tubule hierarchy, decreased spermatogenic cell counts, decreased sperm concentration and motility, and altered abundance of intestinal microbiota, whereas the combination of probiotics and metformin could restore high-fat-mediated pathophysiological alterations thereby ameliorating spermatogenic disorders in mice. The combination of probiotics and metformin can attenuate inflammation and oxidative stress, while enhancing androgen production to improve testicular spermatogenic function by re-construction intestinal microbiota equilibrium in HFD mice.

This study aimed to investigate the molecular mechanisms by which chronic alcohol consumption impacts female infertility, highlighting significant societal implications. By conducting a comprehensive literature review, we examined existing evidence on the association between long-term alcohol use and female reproductive health. Relevant studies were identified through systematic searches of electronic databases and key journals. We synthesized information on the molecular pathways affected by alcohol consumption, with particular emphasis on oxidative stress, inflammation, and hormonal disruptions. Additionally, we reviewed efforts to address alcohol-related health issues, including public health interventions, regulatory measures, and educational initiatives. Our study found strong evidence linking chronic alcohol consumption to increased mortality rates and a range of preventable diseases globally. Alcohol's effects extend beyond physiological consequences to psychological, social, and economic burdens. Chronic alcohol consumption disrupts hormonal balance and reproductive function, contributing to female infertility. Future research should focus on quantifying mortality risks associated with alcohol consumption, understanding gender-specific patterns in alcohol-related health outcomes, and elucidating the molecular mechanisms underlying female infertility. Addressing these gaps will inform strategies to mitigate the burden of alcohol-induced health issues and promote overall well-being. Collaborative efforts among diverse stakeholders are essential for advancing research agendas and translating findings into effective interventions.