Fetal exposure of Aristolochic Acid I undermines ovarian reserve by disturbing primordial folliculogenesis

作者全名："Liu Qiqi; He Junlin; Chen Xuemei; Hong Yi; Li Fangfang; Geng Yanqing; Zhang Yan; Lamptey, Jones; Chen Zhuxiu; Liu Fangfei; Wang Yingxiong; Mu Xinyi"

作者地址："[Liu Qiqi; Geng Yanqing; Liu Fangfei; Wang Yingxiong; Mu Xinyi] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China; [Liu Qiqi; He Junlin; Chen Xuemei; Hong Yi; Li Fangfang; Geng Yanqing; Zhang Yan; Lamptey, Jones; Chen Zhuxiu; Liu Fangfei; Wang Yingxiong; Mu Xinyi] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China; [He Junlin; Chen Xuemei; Hong Yi; Li Fangfang; Zhang Yan; Chen Zhuxiu] Chongqing Med Univ, Sch Publ Hlth & Management, Lab Reprod Biol, Chongqing 400016, Peoples R China"

通信作者："Mu, XY (通讯作者)，Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:000806377700002

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：236

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Edited by Professor Bing Yan; Aristolochic acid I; Primordial folliculogenesis; NANOS3; SOX9

摘要："The primordial follicle pool established in early life determines the ovarian reserve in the female reproductive lifespan. Premature exhaustion of primordial follicles contributes to primary ovarian insufficiency (POI), that is dependent by the initial size of the primordial follicle pool and by the rate of its activation and depletion. AAI, a powerful nephrotoxin with carcinogenic potential, is present in the Aristolochiaceae species, which can release AAI into soil as a persistent pollutant. In order to assess the potential risk of Aristolochic Acid I (AAI) exposure on mammalian oogenesis, we uncovered its adverse effect on primordial folliculogenesis in the neonatal mouse ovary and its effect on female fertility in adulthood. Pregnant mice were orally administrated with doses of AAI without hepatic or renal toxicity during late-gestation. Ovaries from offspring of administered female displayed gross aberrations during primordial folliculogenesis. Also, unenclosed oocytes in germ-cell cysts showed increased DNA damage. Furthermore, several key factors, including NANOS3, SOX9, KLF4, that govern early gonad's differentiation were abnormally expressed in the exposed ovary, while the follicle formation was partially restored by knockdown of Nanos3 or sox9. In adulthood, these aberrations evolved into a significant reduction in offspring number and impaired ovarian reserve. Together, our results show that AAI influences primordial folliculogenesis and, importantly, affected female fertility. This study shows that administration of drugs herbs or consumption of vegetables that contain AAs during pregnancy may adversely influence the fertility of offspring."

基金机构："Na-tional Natural Science Foundation of China [32070851, 31601200]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0135]"

基金资助正文："We would like to thank Pro. Liu Xueqing, Dr. Gao Rufei and Dr. Liu Taihang in Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University for their advice on our experimental design. This work was supported by grants from the Na-tional Natural Science Foundation of China (32070851, 31601200) and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0135) ."