PDF(Pubmed)
Abstract：
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.
摘要：
职业化学4-乙烯基环己烯二环氧化物（VCD）是一种生殖毒性的环境污染物，会导致卵泡衰竭，导致卵巢早衰（POI），这显著影响女性的身体健康和生育能力。研究VCD的致病机制可以为预防卵巢损害和POI的治疗提供见解。本研究通过对雌性C57BL/6小鼠腹腔注射VCD15天建立POI小鼠模型。然后将结果与对照组的结果进行比较，包括表型特征和转录组差异的比较，在两个时间点:第15天和第30天。通过对差异表达基因(DEGs)的综合分析,用RT-PCR对一些关键基因进行了鉴定和验证。结果显示对性激素水平有显著影响，卵泡数,以及第15天和第30天VCD诱导的POI小鼠的发情周期。在第15天获得的DEGs和富集结果不如在第30天获得的那些显著。这项研究的结果提供了一个初步的迹象，类固醇激素的合成，DNA损伤修复,卵母细胞有丝分裂受损是VCD介导的卵巢功能障碍的关键。这种功能障碍可能是由原始卵泡池的VCD损伤引起的，随着时间的推移，损害卵泡发育和加重卵巢损伤，使卵巢逐渐难以执行其正常功能。
