Reproductive Sciences最新文献

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.

Obesity leads to menstrual dysfunction by impacting the "hypothalamic-pituitary-ovarian axis" in women, which can result in polycystic ovary syndrome (PCOS). The differentially expressed genes (DEGs) between the PCOS and control groups were identified using a public database, By intersecting these DEGs with key module genes and obesity related genes (ORGs), we obtained 75 differentially expressed ORGs (DE-ORGs). Further screening using machine learning led to the identification of five potential diagnostic biomarkers: CPT1A, LARS2, GSTP1, TREX1, and PILRB. The expression levels of biomarkers exhibited notable variations between the control and PCOS group, with area under curve (AUC) values exceeding 0.89 for all biomarkers, confirming their role as molecular diagnostic biomarkers for PCOS. The AUC of nomogram achieved 1, indicating its perfect predictive capability for PCOS occurrence. Single-cell analysis highlighted the crucial roles of GSTP1 and epithelial cells in the early stages of PCOS development. This study clarifies the roles of these diagnostic biomarkers, offering a theoretical foundation for the clinical assessment and treament of the disease.

Environmental and genetic factors are related to the pathogenesis of preeclampsia (PE). Cytochrome P450 2E1 (CYP2E1) is crucial for the metabolism of endogenous and xenobiotic substances, possibly involved in the pathophysiology of PE. This study explored the association between CYP2E1 96-bp insertion/deletion (I/D) and rs2031920 (C-1054T) genetic variants and the risk of PE in 335 patients with PE and 1301 healthy pregnant women. The CYP2E1 C-1054T variant was linked to an elevated risk of PE according to the dominant, genotype, and allele genetic models (P < 0.05). The genotype TT + CT remained a significant predictor of PE in the logistic regression model including age, gestational age, and body mass index at delivery (OR = 1.606, 95% CI: 1.137-2.286; P = 0.007). Moreover, the combined genotype TT + CT/II + ID of the C-1054T and 96-bp I/D variants further heightened the risk of PE, with the combined genotype DD/CC serving as the reference category (OR = 2.383, 95% CI: 1.381-4.106, P = 0.002). Furthermore, patients with the -1054T allele had lower serum albumin levels and total antioxidant capacity, and more severe proteinuria than those with the CC genotype (P < 0.05), and patients with the 96-bp I allele had a relatively higher atherosclerosis index than those with the DD genotype (P = 0.057). No significant differences in genotype frequencies of PE with severe features, platelet count, serum hepatic enzyme activities and creatinine levels were observed according to the different genotypes (P > 0.05). We conclude that the T allele of the C-1054T variant and its integration with the I allele of the 96-bp I/D variant in CYP2E1 are linked to an elevated risk of PE in Chinese women.

Ex utero embryo culture is one of the important tasks that has not been completely solved. In the first part of the current review, we focus on potential roles ex utero mammalian embryo culture could play, such as in infertility treatment or ex utero embryo treatment. Particularly, we discuss ex utero genetic therapy of embryos for correction and prevention of congenital pathologies. We also discuss the benefits of ex utero embryo culture in comparison to the traditional surrogacy programs and review its potential influence on social aspects. In the second part, we discuss key methods for ex utero embryo culture, their limitations, bottlenecks and blank points. Moreover, we analyze methods of artificial embryo production using stem cells and possible uses of such embryos (including those that reproduce stages of postimplantation development) in scientific research. We discuss the risks of using the described technologies and possible approaches that will avoid these risks.

The genetic etiology is unknown for 30-40% of men with congenital bilateral absence of the vas deferens (CBAVD) and 70% of those with congenital unilateral absence of the vas deferens (CUAVD). The study aimed to investigate the genetic etiology of CBAVD/CUAVD, both with and without renal anomalies, in individuals who are negative for CFTR pathogenic variants. We included 19 cases of congenital absence of vas deferens (CAVD) that were negative for CFTR variants on Sanger sequencing. Whole-exome sequencing (WES) was performed in 16 men with CAVD. Targeted resequencing was carried out in a total of 19 CAVD cases [16 CAVD cases for which WES was performed and an additional 3 CBAVD cases without renal anomalies]. A novel, hemizygous ADGRG2 pathogenic variant (c.1706 C > T; p.T569I) was identified in two men with CBAVD without renal anomalies. Additionally, we detected pathogenic variants in AR, NCKPAL1, FSHR, and SLC26A4 genes in CBAVD without renal anomalies. Pathogenic variants were detected in FREM1, WNT2B, and TBX6 genes in CBAVD men with renal abnormalities. No variants were detected in CUAVD with renal anomalies. In addition to a novel pathogenic variant in the ADGRG2 gene, we report novel candidate genes AR, NCKPAL1, FSHR, and SLC26A4, for CBAVD. We identified variants in the FREM1, WNT2B, and TBX6 genes in CBAVD with renal anomalies. ADGRG2 testing could be useful for appropriate genetic counselling for the X-linked transmission of the molecular defect in CFTR-negative CBAVD. We recommend whole-exome sequencing for genetic screening of CBAVD for CFTR, ADGRG2, and other candidate genes prior to undergoing Intracytoplasmic sperm injection (ICSI).

Male infertility remains a significant global reproductive health challenge, frequently attributed to genetic mutations impairing spermatogenesis and sperm function. This narrative review aims to explore the genetic and molecular underpinnings of male infertility and evaluate the emerging role of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR/Cas9) genome editing as a diagnostic and therapeutic tool, while addressing its associated ethical, technical, and safety considerations. A Comprehensive literature search was conducted across PubMed, Scopus, Web of Science databases, covering studies published between September 1992 and April 2025. Keywords included "male infertility," "genetic causes of male infertility," "genome editing," "CRISPR/Cas9 and male infertility," "genome editing in male reproduction," "ethical concerns of CRISPR," and "future fertility treatments." Eligible studies focused on genetic correction strategies, spermatogonial stem cell applications, off-target effects, mosaicism, and ethical implications of gene editing. The review synthesizes current knowledge on genetic and epigenetic etiologies of male infertility. It discusses the therapeutic potential of CRISPR/Cas9 in correcting these defects and restoring fertility in preclinical models. Critical challenges, including off-target gene editing, germline mosaicism, long-term safety, and ethical debates surrounding human germline modification, were examined. The review also considers future advancements in genome editing and artificial sperm development. CRISPR/Cas9 represents a transformative platform in reproductive medicine with promising implications for treatment of genetically linked male infertility. However, its clinical translation demands rigorous validation, transparent ethical deliberation, and robust regulatory frameworks. Future innovations combining genome editing, regenerative biology, and precision diagnostics may revolutionize fertility care, but must proceed with caution to ensure safety, efficacy, and ethical integrity.