Pubertal lead exposure affects ovary development, folliculogenesis and steroidogenesis by activation of IRE1α-JNK signaling pathway in rat

内分泌学 内科学 发情周期 卵巢 卵泡发生 生物 睾酮(贴片) 信号转导 醋酸铅 男科 医学 怀孕 哺乳期 毒性 细胞生物学 遗传学
作者
Dan Shan,Wen Xin,Xiaoju Guan,Hangping Fang,Yijia Liu,Mengjie Qin,Hu Wang,Jingfeng Xu,Jieqiang Lv,Junzhao Zhao,Haolin Chen
出处
期刊:Ecotoxicology and Environmental Safety [Elsevier]
卷期号:257: 114919-114919 被引量:3
标识
DOI:10.1016/j.ecoenv.2023.114919
摘要

Epidemic studies showed that lead exposures are associated with various female reproductive dysfunctions, including infertility, miscarriage, preterm delivery, and early menopause. However, the mechanism involved is still unclear. In the current study, SD rats were exposed to lead at doses of 0, 5, 25, 50 or 250 mg/L through drinking water from postnatal day 21-56. Lead exposures did not affect the body weight or ovary weight. However, the puberty initiation (ages by which vagina opens and estrous cycle occurs) was significantly delayed by as many as 5.8 and 6.8 days respectively (P < 0.05). Also, lead exposures disrupted the estrous cycles, reduced the numbers of primordial and primary follicles and increased the number of atretic follicles by adult. Furthermore, for the highest does group, serum levels of progesterone and testosterone decreased by 80.2% (P < 0.01) and 49.9% (P < 0.05) respectively, while estradiol level increased by 69.8% (P < 0.01). Western blot analyses indicated that lead exposures specifically down-regulated the expressions of steroidogenic protein STAR, CYP17A1, and HSD3B1, while up-regulated FSHR and CYP19A1. Also, the exposure stimulated the endoplasmic reticulum stress (ERS)-related IRE1α-JNK signaling pathway members. Such activation may also result in apoptosis since the death-signaling molecules CHOP and cleaved-CASP3 were up-regulated while BCL2 was down-regulated. In conclusion, lead exposure during juvenile and puberty significantly affected ovary development and functions. The effects may relate to ERS response since the 6 members related to the pathway were all consistently activated.
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