孕期镉暴露的父系遗传效应对子代卵巢颗粒细胞激素合成障碍的影响。

Paternal genetic effects of cadmium exposure during pregnancy on hormone synthesis disorders in ovarian granulosa cells of offspring.

机构信息

Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environmental Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, Fujian Province, China.

Key Laboratory of Environment and Female Reproductive Health, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

出版信息

J Ovarian Res. 2023 May 16;16(1):98. doi: 10.1186/s13048-023-01175-5.

DOI:10.1186/s13048-023-01175-5

PMID:37194017

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10186638/

Abstract

The aim of this study was to investigate the paternal genetic intergenerational and transgenerational genetic effects of cadmium (Cd) exposure during pregnancy on estradiol (E) and progesterone (Pg) synthesis in the ovarian granulosa cells (GCs) of offspring. Pregnant SD rats were intragastrically exposed to CdCl (0, 0.5, 2.0, 8.0 mg/kg) from days 1 to 20 to produce the F1 generation, F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was obtained in the same way. Using this model, Cd-induced hormone synthesis disorders in GCs of F1 have been observed [8]. In this study, altered serum E and Pg levels in both F2 and F3 generations showed a nonmonotonic dose‒response relationship. In addition, hormone synthesis-related genes (Star, Cyp11a1, Cyp17a1, Cyp19a1, Sf-1) and miRNAs were observed to be altered in both F2 and F3. No differential changes in DNA methylation modifications of hormone synthesis-related genes were observed, and only the Adcy7 was hypomethylated. In summary, paternal genetic intergenerational and transgenerational effects exist in ovarian GCs E and Pg synthesis disorders induced by Cd during pregnancy. In F2, the upregulation of StAR and CYP11A1, and changes in the miR-27a-3p, miR-27b-3p, and miR-146 families may be important, while changes in the miR-10b-5p and miR-146 families in F3 may be important.

摘要

本研究旨在探讨孕期镉（Cd）暴露对子代卵巢颗粒细胞（GCs）中雌二醇（E）和孕酮（Pg）合成的亲代遗传跨代遗传效应。SD 孕鼠从第 1 天到第 20 天经胃内给予 CdCl2（0、0.5、2.0、8.0mg/kg），产生 F1 代，F1 雄性与新购雌性交配产生 F2 代，同样方法获得 F3 代。利用该模型，观察到 Cd 诱导 F1 GCs 中激素合成紊乱[8]。本研究中，F2 和 F3 代血清 E 和 Pg 水平改变均呈现非单调剂量反应关系。此外，F2 和 F3 代中与激素合成相关的基因（Star、Cyp11a1、Cyp17a1、Cyp19a1、Sf-1）和 miRNA 也发生改变。未观察到与激素合成相关基因的 DNA 甲基化修饰发生差异变化，仅 Adcy7 呈低甲基化。综上所述，孕期 Cd 致卵巢 GCs E 和 Pg 合成障碍存在亲代遗传跨代遗传效应。在 F2 中，StAR 和 CYP11A1 的上调，miR-27a-3p、miR-27b-3p 和 miR-146 家族的变化可能是重要的，而 F3 中 miR-10b-5p 和 miR-146 家族的变化可能是重要的。