Transcriptome analysis during 4-vinylcyclohexene diepoxide exposure-induced premature ovarian insufficiency in mice.

The occupational chemical 4-Vinylcyclohexene diepoxide (VCD) is a reproductively toxic environmental pollutant that causes follicular failure, leading to premature ovarian insufficiency (POI), which significantly impacts a woman's physical health and fertility. Investigating VCD's pathogenic mechanisms can offer insights for the prevention of ovarian impairment and the treatment of POI. This study established a mouse model of POI through intraperitoneal injection of VCD into female C57BL/6 mice for 15 days. The results were then compared with those of the control group, including a comparison of phenotypic characteristics and transcriptome differences, at two time points: day 15 and day 30. Through a comprehensive analysis of differentially expressed genes (DEGs), key genes were identified and validated some using RT-PCR. The results revealed significant impacts on sex hormone levels, follicle number, and the estrous cycle in VCD-induced POI mice on both day 15 and day 30. The DEGs and enrichment results obtained on day 15 were not as significant as those obtained on day 30. The results of this study provide a preliminary indication that steroid hormone synthesis, DNA damage repair, and impaired oocyte mitosis are pivotal in VCD-mediated ovarian dysfunction. This dysfunction may have been caused by VCD damage to the primordial follicular pool, impairing follicular development and aggravating ovarian damage over time, making it gradually difficult for the ovaries to perform their normal functions.

The NFκB Signaling Pathway Is Involved in the Pathophysiological Process of Preeclampsia.

The high prevalence of preeclampsia (PE) is a major cause of maternal and fetal mortality and affects the long-term prognosis of both mother and baby. Termination of pregnancy is currently the only effective treatment for PE, so there is an urgent need for research into its pathogenesis and the development of new therapeutic approaches. The NFκB family of transcription factors has an essential role in inflammation and innate immunity. In this review, we summarize the role of NFκB in normal and preeclampsia pregnancies, the role of NFκB in existing treatment strategies, and potential NFκB treatment strategies.

Understanding the Mechanisms of Diminished Ovarian Reserve: Insights from Genetic Variants and Regulatory Factors.

Delaying childbearing age has become a trend in modern times, but it has also led to a common challenge in clinical reproductive medicine-diminished ovarian reserve (DOR). Since the mechanism behind DOR is unknown and its clinical features are complex, physicians find it difficult to provide targeted treatment. Many factors affect ovarian reserve function, and existing studies have shown that genetic variants, upstream regulatory genes, and changes in protein expression levels are present in populations with reduced ovarian reserve function. However, existing therapeutic regimens often do not target the genetic profile for more individualized treatment. In this paper, we review the types of genetic variants, mutations, altered expression levels of microRNAs, and other related factors and their effects on the regulation of follicular development, as well as altered DNA methylation. We hope this review will have significant implications for the future treatment of individuals with reduced ovarian reserve.

Adverse effects of type 2 diabetes mellitus on ovarian reserve and pregnancy outcomes during the assisted reproductive technology process.

Objective: To study the effect of type 2 diabetes mellitus(T2DM)on overall ovarian reserve and pregnancy outcomes during assisted reproductive technology (ART) among childbearing infertile women. Design: Retrospective cohort study. Setting: The Reproductive Medicine Special Hospital, The First Hospital of Lanzhou University, between January 2019 and December 2022. Patients: A total of 265 infertile female patients aged 20-45 years who underwent in vitro fertilization-embryo transfer (IVF-ET), intracytoplasmic sperm injection-embryo transfer (ICSI-ET), or rescue intracytoplasmic sperm injection-embryo transfer (RICSI-ET) in the first fresh cycle. Interventions: None. Main Outcome Measures: Serum Anti-Müllerian Hormone (AMH) levels, clinical pregnancy rate (CPR), live birth rate (LBR), and abortion rate (AR) in the T2DM group and non-T2DM group. Results: Patients with T2DM showed statistically decreased levels of AMH compared to the non-T2DM group. During ovarian stimulation, those with T2DM required significantly higher total and initial doses of gonadotropin (GN), although they had fewer retrieved oocytes and worse pregnancy outcomes than the non-T2DM group. Multivariate logistic regression analysis adjusting for confounding factors showed that T2DM alone was an independent risk factor for CPR and LBR (adjusted odds ratio [a OR], 0.458, adjusted 95% confidence interval [CI], 0.235-0.891, P = 0.022; a OR, 0.227, 95% CI, 0.101-0.513, P<0.001; respectively), and the abortion rate in the T2DM group was 3.316 times higher than the non-T2DM group(a OR, 3.316, 95%CI, 1.248-8.811, P = 0.016). Conclusion: Infertile patients with T2DM have decreased ovarian reserve, and T2DM has a deleterious impact on clinical pregnancy outcomes during the ART process compared with non-T2DM infertile women. Capsule: Infertile women with T2DM have decreased ovarian reserve and pregnancy outcomes during the assisted reproductive technology process compared with non-T2DM infertile women.

Potential factors result in diminished ovarian reserve: a comprehensive review.

The ovarian reserve is defined as the quantity of oocytes stored in the ovary or the number of oocytes that can be recruited. Ovarian reserve can be affected by many factors, including hormones, metabolites, initial ovarian reserve, environmental problems, diseases, and medications, among others. With the trend of postponing of pregnancy in modern society, diminished ovarian reserve (DOR) has become one of the most common challenges in current clinical reproductive medicine. Attributed to its unclear mechanism and complex clinical features, it is difficult for physicians to administer targeted treatment. This review focuses on the factors associated with ovarian reserve and discusses the potential influences and pathogenic factors that may explain the possible mechanisms of DOR, which can be improved or built upon by subsequent researchers to verify, replicate, and establish further study findings, as well as for scientists to find new treatments.

Effects of Solidago canadensis L. on mineralization-immobilization turnover enhance its nitrogen competitiveness and invasiveness.

The effects of exotic plants on soil nitrogen (N) transformations may influence species invasion success. However, the complex interplay between invasive plant N uptake and N transformation in soils remains unclear. In the present study, a series of 15N-labeled pot experiments were carried out with Solidago canadensis L. (S. canadensis), an invasive plant, and the Ntrace tool was used to clarify the preferred inorganic N form and its effects on soil N transformation. According to the results, nitrate-N (NO3--N) uptake rates by S. canadensis were 2.38 and 2.28 mg N kg-1 d-1 in acidic and alkaline soil, respectively, which were significantly higher than the ammonium-N (NH4+-N) uptake rates (1.76 and 1.56 mg N kg-1 d-1, respectively), indicating that S. canadensis was a NO3--N-preferring plant, irrespective of pH condition. Gross N mineralization rate was 0.41 mg N kg-1 d-1 in alkaline soil in the presence of S. canadensis L., which was significantly lower than that in the control (no plant, CK, 2.44 mg N kg-1 d-1). Gross autotrophic nitrification rate also decreased from 5.95 mg N kg-1 d-1 in the CK to 0.04 mg N kg-1 d-1 in the presence of S. canadensis in alkaline soil. However, microbial N immobilization rate increased significantly from 1.09 to 2.16 mg N kg-1 d-1, and from 0.02 to 2.73 mg N kg-1 d-1 after S. canadensis planting, in acidic and alkaline soil, respectively. Heterotrophic nitrification rate was stimulated in the presence of S. canadensis to provide NO3--N to support the N requirements of plants and microbes. The results suggested that S. canadensis can influence the mineralization-immobilization turnover (MIT) to optimize its N requirements while limiting N supply for other plants in the system. The results of the present study enhance our understanding of the competitiveness and mechanisms of invasion of alien plants.

Identification of Common and Specific Genes Involved in Mouse Models of Age-Related and Cyclophosphamide-Induced Diminished Ovarian Reserve.

Diminished ovarian reserve (DOR) is an etiologically heterogeneous disorder that usually leads to poor reproductive outcomes. Does a specific or common pathogenesis exist for DOR subtypes with different etiologies? Two frequently used mouse models, age-related DOR (AR-DOR) and cyclophosphamide (CTX)-induced DOR (CTX-DOR), were successfully established, and RNA sequencing was performed on ovarian tissue samples. Differentially expressed genes (DEGs) in each subtype and common DEGs (co-DEGs) in the two subtypes were identified. Subsequently, we performed comprehensive bioinformatics analyses, including an evaluation of immune cell infiltration. Finally, the genes of interest were further validated by performing RT-qPCR and immunohistochemistry. In AR-DOR mice, functional enrichment analyses showed that upregulated DEGs were mainly involved in the inflammatory/immune response, while downregulated DEGs were involved in DNA damage repair. In CTX-DOR mice, the inflammatory/immune response and cell apoptosis played significant roles. Meanwhile, 406 co-DEGs were identified from the two models. The biological functions of these co-DEGs were associated with inflammatory/immune responses. The analysis of immune cell infiltration showed reduced infiltration of Treg cells, as well as increased infiltration of M0 macrophages, NK resting, and T cells CD4 follicular in both DOR subtypes. The results of the validation experiments were consistent with the RNA sequencing data. In conclusion, the inflammatory/immune response might be the common pathogenesis for the two DOR subtypes, while DNA repair and cell apoptosis may have different roles in the two subtypes. These results may provide potential insights for mechanistic research and therapeutic targets of DOR.

Decreased fatty acids induced granulosa cell apoptosis in patients with diminished ovarian reserve.

PURPOSE: To investigate whether fatty acid changes in granulosa cells (GCs) underly the pathogenic mechanisms of diminished ovarian reserve (DOR). METHODS: GCs were obtained from patients with DOR (n = 70) and normal ovarian reserve (NOR, n = 70). Analysis of fatty acids changes in GCs was then analyzed. RESULTS: Patients with DOR had significantly lower levels of antral follicle count and anti-Mullerian hormone and higher levels of follicle-stimulating hormone compared with NOR patients (P < 0.001). The good-quality embryo rate was notably decreased in DOR patients (51.99 vs 39.52%, P < 0.05). A total of 15 significantly decreased fatty acids in GCs from patients with DOR. The ATP levels were markedly lower in DOR patients than in NOR patients (39.07 ± 12.89 vs 23.21 ± 13.69%, P < 0.05). Mitochondrial membrane potential decreased in DOR patients (P < 0.01). In GCs from DOR patients, the ß-oxidation genes (HADHA and ACSL) and DNA repair genes (PRKDC and RAD50) were significantly downregulated (P < 0.05). The γH2AX foci/nucleus ratio in DOR patients markedly increased relative to that of NOR patients (0.31 ± 0.03 vs 0.87 ± 0.07, P < 0.001). Meanwhile, the apoptosis rate of GCs was significantly higher in DOR patients (6.43 ± 2.11 vs 48.06 ± 6.72%, P < 0.01). CONCLUSION: GC apoptosis resulting from the decrease of fatty acids, and associated with reduced ATP production and DNA damage, may contribute to the pathogenic mechanisms responsible for DOR.

Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide.

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.