Reproductive Sciences最新文献

Primary ovarian insufficiency (POI) has become a serious problem causing infertility and endocrine disorders in women of child-bearing age. There is an urgent demand for novel drugs or targets to address the apoptosis, autophagy and mitochondria damage associated with ovarian aging. This study focused on the regulation of zygote arrest 1 (ZAR1) in ovarian function and its potential role in POI. We collected clinical samples, established POI cell and mouse models using 4-vinylcyclohexene diepoxide (VCD), and investigated the effects of ZAR1 in KGN cells and POI mice. We found that ZAR1 expression was negatively associated with follicle-stimulating hormone (FSH) in POI women. ZAR1 overexpression inhibited apoptosis activation, cell cycle arrest and mitophagy, but the protection effects can be blocked by autophagy inhibitor. Mice with lower expression of ZAR1 exhibited more severe ovarian damages. These findings indicated that ZAR1 is a novel target for prevention and treatment of ovarian aging.

Insomnia affects most pregnant women. This systematic review aims to examine regarding gestational insomnia and its consequences on pregnant women and neonates. We performed a systematic search of seven databases for English and Chinese language articles about the association between insomnia and maternal complications and adverse fetal outcomes from inception to July 2022 then updated the search date to April 2024. We included observational studies concerning gestational insomnia and one or more adverse maternal, delivery, or neonatal outcomes. Data extraction was completed independently by two reviewers. The quality assessment was analyzed with the Newcastle-Ottawa quality assessment scale and an 11-item checklist recommended by Agency for Healthcare Research and Quality for observational cohort and cross-sectional studies. Data analysis was carried out through meta-analysis and narrative synthesis. Twenty-three identified studies (fifteen cohort studies, six cross-sectional studies and two case-control studies) examined the associations of gestational insomnia with adverse maternal and infant outcomes. The most consistent associations were observed between gestational insomnia and increased risks of perinatal depression (OR = 2.30, 95%CI:1.77,2.96, P = 0.002), perinatal anxiety and postpartum pain. There were mixed findings for post-traumatic stress disorder and low birth weight. Gestational insomnia was not associated with cesarean delivery (OR = 0.92, 95%CI: 0.61,1.38, P = 0.328), gestational hypertension (OR = 1.06, 95%CI: 0.90,1.25, P = 0.526), pre-eclampsia (OR = 1.67, 95%CI:0.21,13.44, P = 0.01), gestational diabetes (OR = 0.77, 95%CI: 0.48,1.24, P = 0.78), preterm birth (OR = 1.09, 95%CI:0.75,1.58, P = 0.073), high birth weight or low Apgar scores. There is an association between insomnia and some adverse maternal and infant outcomes, but larger samples and well-designed prospective studies are still needed to determine their relationship in the future.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder in women. Oxidative stress (OS) plays a pivotal role in the pathogenesis of PCOS. Resveratrol, as a natural polyphenol, has several beneficial therapeutic effects for women with PCOS. In this study, we investigated the antioxidant effect of resveratrol on OS markers in follicular fluid (FF) and granulosa cells (GCs) of patients with PCOS. A total of fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The main focus was on evaluating OS markers, such as malondialdehyde (MDA) and total thiol (sulfhydryl) content in FF, along with assessing the levels of total antioxidant capacity (TAC) and total oxidant status (TOS) in GCs. Additionally, secondary outcomes included measuring the expression of genes associated with OS responses (Manganese superoxide dismutase (Mn-SOD), catalase (CAT), and uncoupling protein 2 (UCP2)), as well as the expression of UCP2 protein in granulosa cells. Compared with the placebo group, resveratrol reduced MDA and conversely significantly increased total thiol (P = 0.6694 and P = 0.0318, respectively) in FF. Resveratrol significantly reduced TOS and oxidative stress index (OSI) (P = 0.0299 and P = 0.0144, respectively) and significantly increased TAC (P = 0.0484) in GCs. There were significant increases in CAT and UCP2 expression after resveratrol consumption (P = 0.0158 and P = 0.0004, respectively). Although resveratrol increased Mn-SOD expression (P = 0.0914), its effects were not statistically significant. Resveratrol significantly affected UCP2 protein levels (P = 0.0030). These findings suggested that 60 days of supplementation with 800 mg/day resveratrol improves markers of OS in the FF and GCs of patients with PCOS. Trial registration number: http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

PCOS refers to an endocrine and metabolic disorder that affects female individuals of reproductive age. Our study explores the potential mechanism of circ_0070987 on PCOS in regulating pyroptosis of ovarian GCs, providing new evidence for PCOS treatment. PCOS cell model was established. The expression of circ_0070987, line ELF2, miR-139-5p and CDH1 was detected. Cell viability was measured. The expression of IL-1β, IL-18, NLRP3, cleaved Caspase-1, GSDMD-N, and CDH1 was analyzed. Circ_0070987 was downregulated to verify its effect on pyroptosis. The binding of miR-139-5p to circ_0070987 and CDH1 was verified by dual-luciferase report assay. The role of circ_0070987 in pyroptosis of ovarian GCs in PCOS through the miR-139-5p/CDH1 axis was validated. After DHT treatment, cell viability of SVOG was decreased, and the expression of IL-1β, IL-18, circ_0070987, NLRP3, cleaved Caspase-1 and GSDMD-N was increased. DHT-induced pyroptosis of ovarian GCs was inhibited upon circ_0070987 downregulation. Mechanistically, circ_0070987 negatively regulated miR-139-5p, which targeted and inhibited CDH1. Inhibitory effect of circ_0070987 downregulation on pyroptosis of ovarian GCs in PCOS was reduced after miR-139-5p downregulation or CDH1 overexpression. In conclusion, circ_0070987 inhibits miR-139-5p expression and upregulates CDH1 expression, thus promoting pyroptosis of ovarian GCs in PCOS.

Because of the lack of fully successful treatment of low-risk gestational trophoblastic neoplasia (GTN) patients after first-line single-agent chemotherapy, some studies have suggested that these patients should be treated with multi-drug chemotherapy from the outset. A score of 0-4 represents the majority of low risk GTN that has been less studied. The present study aimed to investigate the risk factors associated with resistance to first-line single-agent chemotherapy. This retrospective cohort includes patients diagnosed with low-risk GTN who were treated with single-agent chemotherapy using methotrexate and actinomycin. Factors associated with resistance to first-line chemotherapy were analyzed separately in two groups: those with a score of 0-6 and those with a score of 0-4. A total of 270 patients were studied, all of whom achieved remission. Of these, 75.9% responded to first-line single-agent chemotherapy. Patients aged 40 or older had about 7 times higher odds of treatment resistance than younger patients. Choriocarcinoma increased the odds by 5.5 times, and each 1 cm increase in tumor size raised the odds by 53%. In patients with WHO scores of 0-4, each additional year of age increased resistance odds by 6%, and choriocarcinoma raised it by 7.5 times. In both groups, lung metastasis increased the chance of resistance threefold. Increased age, larger tumor size, increase βhCG level and start of treatment with MTX, increase the likelihood of resistance to first-line chemotherapy in the 0-6 score and in the subgroup with a 0-4 score. Future prospective studies are necessary to validate new models Until then, clinicians should be aware of the limitations of the current system and consider individualized clinical judgment.

Ovarian aging leads to a decline in oocyte quality and reduced reproductive potential, which is one of the main challenges faced by assisted reproductive technology (ART). Oxidative stress (OS) is a major contributor to this decline. In this study, we investigated the protective effects of natural flavonoid compound liquiritigenin (LQ) on oocyte maturation and embryo development in aged mice. The results showed that 20 μM LQ significantly improved the maturation rate of aged oocytes, restored spindle morphology, and enhanced fertilization and two-cell embryo development rates. Mechanism studies have found that LQ reduces the levels of reactive oxygen species (ROS) in oocytes and restores mitochondrial function, including distribution patterns and membrane potential. Additionally, LQ upregulated the protein expression of Sirtuin 1 (SIRT1) and nuclear factor E2-related factor 2 (NRF2) in the ovaries and oocytes of aging mice, as well as in the human ovarian granulosa tumor cell line (KGN). Although its mRNA level showed minimal change, it suggested that it might play a role through post-translational regulation. These results suggest that LQ protects aged oocytes from oxidative stress by activating the SIRT1/NRF2 signaling pathway, highlighting its potential as a natural antioxidant for alleviating ovarian aging and improving oocyte quality.

Background and objective: As space exploration advances, the effects of the microgravity environment on testicular injury and spermatogenic function in astronauts have attracted widespread attention, but the underlying mechanisms remain unclear.

Methods: In this study, testicular morphometry and Johnsen score were used to evaluate the degree of testicular injury. Then the upstream transcription factors of MeCP2 were verified using the dual-luciferase reporter assay. Finally, the expression of C/EBP-β, MeCP2, and Wnt4/β-Catenin protein was detected to clarify the regulatory pathway.

Results: Under microgravity conditions, MeCP2 expression was significantly reduced in rat testes and was positively correlated with testicular morphometric indices. Subsequently, the dual-luciferase reporter assay revealed that C/EBP-β directly bound to the promoter sequence of MeCP2, initiating its transcriptional activity. Meanwhile, the expression of C/EBP-β, Wnt4, and β-Catenin was reduced in the testes under microgravity conditions.

Conclusions: In conclusion, our study proposed that C/EBP-β regulated MeCP2, consequently, inhibited the Wnt4/β-Catenin pathway activity, thereby participating in microgravity-induced testicular injury.

To assess the relationship between blastulation, ICM (inner cell mass) quality, TE (trophectoderm) quality, embryo sex, or embryo sex selection and live birth among euploid embryos. Single-center retrospective cohort analysis of patients who underwent single frozen embryo transfer (FET) following autologous IVF with preimplantation genetic testing for aneuploidy from 2020-2021. Blastocysts underwent trophectoderm biopsy with ICM and TE grading before vitrification. The associations between live birth (LB) and patient/embryo characteristics were assessed with mixed-effect multivariable logistic regression. In 768 euploid FET cycles with available live birth data, 404 cycles (52.6%) resulted in live birth. A significantly lower odds of LB was seen with vitrification on days 6 and 7 compared to day 5 (aOR 0.81, 95% CI 0.70-0.95) and in embryos with lower ICM quality compared to those with quality 1, the highest of three quality grades and indicative of tightly packed cells (aOR 0.75, 0.62-0.90). Embryo sex was known in > 90% of transferred embryos, with 355 (50.8%) female and 344 (49.2%) male. In 161 (21.0%) cycles where embryo sex was used to select embryo for transfer with 84 (52.2%) male and 77 (47.8%) female, embryo sex and embryo sex selection were not significantly associated with the odds of LB. Prioritizing embryos for transfer with better ICM quality and earlier blastulation may provide the highest chance of LB. Trophoblast quality at vitrification, embryo sex, and embryo sex selection were not associated with the odds of LB, but these factors may influence patient and physician decision-making.