PMID- 36864339 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20230425 IS - 1614-7499 (Electronic) IS - 0944-1344 (Linking) VI - 30 IP - 18 DP - 2023 Apr TI - Prenatal BPA exposure disrupts male reproductive functions by interfering with DNA methylation and GDNF expression in the testes of male offspring rats. PG - 53741-53753 LID - 10.1007/s11356-023-26154-7 [doi] AB - BPA is a ubiquitous environmental endocrine-disrupting chemical, and maternal exposure to BPA is associated with impaired male reproductive functions; however, the mechanisms remain to be elucidated. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in maintaining normal spermatogenesis and fertility. However, the effect of prenatal BPA exposure on GDNF expression and its mechanism in the testis has not been reported. In this study, pregnant Sprague-Dawley rats were respectively exposed to 0, 0.05, 0.5, 5, and 50 mg/kg/day BPA via oral gavage from gestational day (GD) 5 to GD 19, with 6 pregnant rats in each group. ELISA, histochemistry, real-time PCR, western blot, and methylation-specific PCR (MSP) were used to detect the sex hormone levels, testicular histopathology, mRNA and protein expression of DNA methyltransferases (DNMTs) and GDNF, and the promoter methylation of Gdnf in the testes of male offspring at postnatal day (PND) 21 and PND 56. Prenatal BPA exposure increased body weight; decreased sperm counts and serum levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH); and induced testicular histological damage, which indicated the damage of male reproductive function. Prenatal BPA exposure also upregulated Dnmt1 in 5 mg/kg group and Dnmt3b in 0.5 mg/kg group, but down-regulated Dnmt1 in 50 mg/kg group at PND 21. At PND 56, Dnmt1 was significantly increased in 0.05 mg/kg group but decreased in 0.5, 5, and 50 mg/kg groups, Dnmt3a was decreased, and Dnmt3b was markedly increased in 0.05 and 0.5 mg/kg groups but decreased in 5 and 50 mg/kg groups. The mRNA and protein expression levels of Gdnf were decreased markedly in 0.5 and 50 mg/kg groups at PND 21. And the methylation level of Gdnf promoter was significantly increased in 0.5 mg/kg group, but decreased in 5 and 50 mg/kg groups at PND 21. In conclusion, our study indicates that prenatal BPA exposure disrupts male reproductive functions, interferes with the expression of DNMTs, and decreases Gdnf expression in the testes of male offspring. Gdnf expression may be regulated by DNA methylation; however, the detailed mechanism needs to be further investigated. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Mao, Yaping AU - Mao Y AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. FAU - Li, Dan AU - Li D AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. FAU - Yang, Qiaoqiao AU - Yang Q AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. FAU - Pei, Xiucong AU - Pei X AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. FAU - Duan, Zhiwen AU - Duan Z AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. FAU - Ma, Mingyue AU - Ma M AUID- ORCID: 0000-0003-4440-1618 AD - Department of Toxicology, School of Public Heath, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. mymacmu@163.com. AD - Department of Key Laboratory of Environmental Pollution and Microecology, Shenyang Medical College, Shenyang, 110034, Liaoning Province, China. mymacmu@163.com. LA - eng GR - 2019-ZD-0317/Natural Science Foundation of Liaoning Province/ GR - 2022-NLTS-14-05/Liaoning Province Innovation Capacity Promotion Joint Fund/ GR - LJKMZ20221782/Scientific Research Foundation of Education Department of Liaoning Province/ PT - Journal Article DEP - 20230303 PL - Germany TA - Environ Sci Pollut Res Int JT - Environmental science and pollution research international JID - 9441769 RN - 0 (Benzhydryl Compounds) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - MLT3645I99 (bisphenol A) SB - IM MH - Animals MH - Female MH - Humans MH - Male MH - Pregnancy MH - Rats MH - Benzhydryl Compounds/metabolism MH - DNA Methylation MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - *Prenatal Exposure Delayed Effects/chemically induced MH - Rats, Sprague-Dawley MH - RNA, Messenger/metabolism MH - Semen/metabolism MH - *Testis OTO - NOTNLM OT - Bisphenol A OT - DNA methyltransferase OT - Glial cell line-derived neurotrophic factor OT - Male offspring OT - Promoter methylation OT - Reproductive function EDAT- 2023/03/03 06:00 MHDA- 2023/04/24 06:42 CRDT- 2023/03/02 23:28 PHST- 2022/08/01 00:00 [received] PHST- 2023/02/23 00:00 [accepted] PHST- 2023/04/24 06:42 [medline] PHST- 2023/03/03 06:00 [pubmed] PHST- 2023/03/02 23:28 [entrez] AID - 10.1007/s11356-023-26154-7 [pii] AID - 10.1007/s11356-023-26154-7 [doi] PST - ppublish SO - Environ Sci Pollut Res Int. 2023 Apr;30(18):53741-53753. doi: 10.1007/s11356-023-26154-7. Epub 2023 Mar 3.