妊娠期接触 PNMC 会干扰卵母细胞减数分裂和精子发生，从而减少后代配子数量

Gestational exposure to PNMC reduces offspring gamete numbers by disrupting oocyte meiosis and spermatogenesis

妊娠期接触 PNMC 会干扰卵母细胞减数分裂和精子发生，从而减少后代配子数量

Authors: Tian Ma, Hui Yu, Xinyu Zhou, Yuqin Wang, Dongying Sun, Zizhuo Cao, Cong Ma, Zhiming Ding, Xiaofeng Xu, Yunxia Cao

Source: Ecotoxicology And Environmental Safety

DOI: 10.1016/j.ecoenv.2025.117980

Abstract

3-Methyl-4-nitrophenol (PNMC) is a prevalent nitrophenolic endocrine disruptor found in pregnant women, with known effects on offspring growth and development. However, its impact on offspring fertility remains unexplored. This study investigates the effects of PNMC exposure during pregnancy on offspring fertility and the underlying mechanisms. Our fertility assessments revealed that PNMC exposure during pregnancy reduced the number of follicles and spermatozoa in offspring, though it did not affect their quality. In male offspring, PNMC exposure impaired spermatogenesis by reducing the number of Sertoli cells and spermatogonia. In female offspring, exposure disrupted the first meiotic prophase (MPI) of oocytes, leading to a reduced number of diplotene oocytes available for primordial follicle assembly. This depletion of primordial follicle reserve ultimately resulted in subfertility. Specifically, PNMC exposure hindered homologous recombination-mediated DNA double-strand break repair, triggering activation of the meiotic checkpoint and leading to MPI arrest. This arrested progression resulted in a depletion of diplotene oocytes. This is the first study to provide comprehensive evidence on the effects of PNMC exposure during pregnancy on offspring reproductive capacity, elucidating key pathways. These findings emphasize the need for stricter regulatory measures to limit PNMC exposure and offer new insights into the etiology of idiopathic oligozoospermia and diminished ovarian reserve.

Keywords: Homologous recombination; Nitrophenol; Pachytene checkpoints; Reproduction; Sertoli cells.

摘要

3-甲基-4-硝基苯酚（PNMC）是一种普遍存在于孕妇体内的硝基苯类内分泌干扰物，已知会对后代的生长和发育产生影响。然而，它对后代生育能力的影响仍未得到研究。本研究调查了孕期接触 PNMC 对后代生育能力的影响及其内在机制。我们的生育力评估结果显示，孕期接触 PNMC 会减少后代卵泡和精子的数量，但不会影响其质量。在男性后代中，接触 PNMC 会减少 Sertoli 细胞和精原细胞的数量，从而损害精子形成。在雌性后代中，接触 PNMC 会破坏卵母细胞的第一个减数分裂前期（MPI），导致可用于原始卵泡组装的二分裂卵母细胞数量减少。原始卵泡储备的耗竭最终导致不育。具体来说，接触 PNMC 会阻碍同源重组介导的 DNA 双链断裂修复，引发减数分裂检查点的激活，导致 MPI 停止。这种停滞的进展导致了双顶体卵母细胞的减少。这项研究首次提供了怀孕期间接触 PNMC 对后代生殖能力影响的全面证据，阐明了关键途径。这些发现强调了采取更严格的监管措施限制接触 PNMC 的必要性，并为了解特发性少精症和卵巢储备功能减退的病因提供了新的视角。

关键词：同源重组；硝基苯酚；细胞周期检查点；生殖；Sertoli细胞