Arsenic exposure during juvenile and puberty significantly affected reproductive system development of female SD rats

Panpan Chen; Qiong Luo; Yifeng Lin; Jiani Jin; Kai-Lun Hu; Feixia Wang; Jiwei Sun; Ruixue Chen; Juan Wei; Guangdi Chen; Dan Zhang

doi:10.1016/j.ecoenv.2022.113857

Arsenic exposure during juvenile and puberty significantly affected reproductive system development of female SD rats

Ecotoxicol Environ Saf. 2022 Sep 1:242:113857. doi: 10.1016/j.ecoenv.2022.113857. Epub 2022 Jul 7.

Authors

Panpan Chen¹, Qiong Luo¹, Yifeng Lin¹, Jiani Jin¹, Kai-Lun Hu¹, Feixia Wang¹, Jiwei Sun¹, Ruixue Chen¹, Juan Wei¹, Guangdi Chen², Dan Zhang³

Affiliations

¹ Key Laboratory of Women's Reproductive Health of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Department of Public Health, and Department of Reproductive Endocrinology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Key Laboratory of Women's Reproductive Health of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: zhangdan@zju.edu.cn.

PMID: 35809398
DOI: 10.1016/j.ecoenv.2022.113857

Abstract

Infertility affects about 10-15% couples over the world, among which a large number of cases the underlying causes are still unclear. Recent studies suggest that environmental factors may play an important role in these idiopathic infertilities. Arsenic is a heavy metal found in drinking water over the world. Its effect on the development of female reproductive system at the environmental-relevant levels is still largely unknown. To test the hypothesis that arsenic exposure during juvenile and puberty may affect sex maturation and female reproductive system development, SD rats of 3 weeks of age were exposed to arsenic with environmental-relevant levels (0, 0.02, 0.2, or 2 mg/L, n = 16/group) through drinking water for about 44 days until the rats reached adulthood (65 days of age). Arsenic exposure significantly reduced the weights of both ovary and uterus without affecting the body weight. Also, arsenic exposure disturbed estrus cycles and reduced the numbers of primordial follicles and corpora lutea while increased atretic follicles. In addition, arsenic reduced serum levels of estradiol, progesterone and testosterone but increased LH and FSH levels in dose-dependent manners. QPCR and Western blot experiments indicated arsenic selectively down-regulated ovarian steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK-JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, arsenic-exposed dams had smaller pups, reduced litter size and lower number of male pups without a change in female pups. In conclusion, juvenile and pubertal arsenic exposures at environmental-relevant levels significantly reduced reproductive functions and capacity by adult. Since the lowest effective dose is very close to the government safety standards, the relevancy of arsenic over exposure to reproductive defects in human deserves further study.

Keywords: Arsenic; Ovarian development; PKA/MAPK/cJUN; Sex hormones; Steroidogenesis; Theca cells.

MeSH terms

Adult
Animals
Arsenic* / metabolism
Drinking Water*
Female
Humans
Male
Ovary
Rats
Rats, Sprague-Dawley
Sexual Maturation

Substances

Drinking Water
Arsenic