Reproductive Biology and Endocrinology最新文献

Background: Mesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as stem cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy and safe handling, in vitro ovarian culture is widely available for drug screening, pathophysiological research, and in vitro fertilization. MSCs could exhibit therapeutic capacity for ovarian injury, and avoid stem cell loss and immune phagocytosis in vitro tissue culture system. Therefore, this study utilizes an in vitro ovarian culture system to investigate the reparative potential of human umbilical cord mesenchymal stem cells (hUCMSCs) and their mechanism.

Methods: In this study, a chemotherapy-induced POF model was established by introducing cisplatin in vitro ovarian culture system. The reparative effects of hUCMSCs on damaged ovarian tissue were validated through Transwell chambers. Tissue histology examination, immunohistochemical staining, Western blotting, and RT-PCR were employed to evaluate the expression effects of hUCMSCs on ferroptosis and fibrosis-related genes during the process of repairing cisplatin-induced POF.

Results: Cisplatin was found to activate ovarian follicles in vitro POF model. Transcriptomic sequencing analysis revealed that cisplatin could activate genes associated with ferroptosis. hUCMSCs alleviated cisplatin-induced POF by suppressing the expression of ferroptosis. Moreover, inhibiting ferroptosis by hUCMSCs also ameliorated ovarian hormone levels and reduced the expression of fibrosis-related factors α-SMA and COL-I in the ovaries.

Conclusions: This study confirms that cisplatin-induced ovarian damage via ferroptosis in vitro POF model, and hUCMSCs repair ovarian injury by inhibiting the ferroptosis pathway and suppressing fibrosis. This research contributes to evaluating the effectiveness of hUCMSCs in treating chemotherapy-induced POF by inhibiting ferroptosis in an in vitro ovarian culture system and provides a potential therapeutic strategy for chemotherapy-induced POF.

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

Background: Epidemiological studies have reported that polymorphisms of folate-metabolizing genes have a significant impact on male infertility. However, the results of published studies have come to different conclusions.

Objective: To determine an association between folate-metabolizing gene polymorphisms and the risk of male infertility.

Methods: The meta-analysis was conducted according to the PRISMA 2020 statement. The protocol was registered with PROSPERO (CRD42023412251). Studies were searched from PubMed, Google Scholar, Embase, Scopus, and the Cochrane Library up to 24st October2023. Articles that satisfied the inclusion criteria were evaluated for their quality using the Newcastle-Ottawa Scale. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Meta-analysis was conducted using STATA 12.

Results: Forty-six case-control studies were included in the meta-analysis which comprised 20,639 participants. The pooled analysis revealed that the MTHFR C677T polymorphism was significantly associated with male infertility and abnormospermia.Three-fifths of the model showed there was a significant association between the MTR A2756G polymorphism and male infertility. Both MTHFR A1298C and MTRR A66G polymorphisms were not significantly associated with male fertility. Furthermore, subgroup analysis revealed a significant association between the MTHFR C677T polymorphism and male fertility in Asian countries.

Conclusion: This meta-analysis suggests that the MTHFR C677T and MTR A2756G polymorphisms may be a potential risk factor for male infertility.

Background: Assisted Reproductive Techniques (ART) have significantly advanced infertility treatment worldwide. However their availability and use in sub-Saharan Africa, remains limited although infertility is highly prevalent, with significant psycho-social challenges including stigma. This study assessed the awareness, attitudes, and perceptions of ART among non-medical tertiary students in Ghana.

Method: A cross-sectional study was conducted among non-medical students in tertiary institutions in Ghana. Pre-tested questionnaires were administered to both post-graduate and undergraduate students after obtaining informed consent. Ethical approval was obtained from the Review Board at Community Health Department of the University of Ghana Medical School. The data collected was analyzed using SPSS (version-27) and the results presented using frequency tables, graphs, and charts. significance was P-value below 0.05 was considered statistically significant.

Results: Overall, 196 participants from the two largest universities and other tertiary institutions in Ghana took part in this study. Majority (63.5%) of respondents demonstrated awareness on ART services, but 60.3% showed poor knowledge of the types of ART. Males generally exhibited lower knowledge of ART services compared to females, and knowledge of ART services showed an inverse relationship with age. In-vitro fertilization (IVF) was the most widely recognized and recommended ART technique, known by 65.1% of respondents who were aware of the types of ART. Most participants expressed reluctance to accept or recommend gamete donation due to religious reasons, fear of complications, and a preference for conventional means of procreation.

Conclusion: The majority of tertiary students in Ghana are aware of ART for infertility treatment however, many are hesitant toward donor-gamete treatment protocols. Fear of complications and related costs pose major barriers to considering ART among the respondents. Participants unanimously suggested government subsidies and the inclusion of ART under the national health insurance coverage package.

Background: Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement.

Methods: Multi-view images of 226 blastocysts on Day 6 were captured by manually rotating blastocysts during the preparation stage of trophectoderm biopsy. Quantitative morphological parameters were obtained by 3D morphology measurement. Six machine learning models were trained using 3D morphological parameters as the input and PGT-A results as the ground truth outcome. Model performance, including sensitivity, specificity, precision, accuracy and AUC, was evaluated on an additional test dataset. Model interpretation was conducted on the best-performing model.

Results: All the 3D morphological parameters were significantly different between euploid and non-euploid blastocysts. Multivariate analysis revealed that three of the five parameters including trophectoderm cell number, trophectoderm cell size variance and inner cell mass area maintained statistical significance (P < 0.001, aOR = 1.054, 95% CI 1.034-1.073; P = 0.003, aOR = 0.994, 95% CI 0.991-0.998; P = 0.010, aOR = 1.003, 95% CI 1.001-1.006). The accuracy of euploidy prediction by the six machine learning models ranged from 80 to 95.6%, and the AUCs ranged from 0.881 to 0.984. Particularly, the decision tree model achieved the highest accuracy of 95.6% (95% CI 84.9-99.5%) with the AUC of 0.978 (95% CI 0.882-0.999), and the extreme gradient boosting model achieved the highest AUC of 0.984 (95% CI 0.892-1.000) with the accuracy of 93.3% (95% CI 81.7-98.6%). No significant difference was found between different age groups using either decision tree or extreme gradient boosting to predict euploid blastocysts. The quantitative criteria extracted from the decision tree imply that euploid blastocysts have a higher number of trophectoderm cells, larger inner cell mass area, and smaller trophectoderm cell size variance compared to non-euploid blastocysts.

Conclusions: Using quantitative morphological parameters obtained by 3D morphology measurement, the decision tree-based machine learning model achieved an accuracy of 95.6% and AUC of 0.978 for predicting euploidy in Day 6 human blastocysts.

Trial registration: N/A.

Background: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.

Methods: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.

Results: With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.

Conclusions: In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

Background: Recent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles.

Methods: In the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles.

Results: Demographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41-3.86, P-value = 0.001).

Conclusion: Pregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.