Maternal exposure to bisphenol A during pregnancy interferes testis development of F1 male mice
This study was conducted to investigate the effects of maternal exposure to bisphenol A (BPA) on testis development of F1 male mice. The BPA exposure model of pregnant mice was prepared by intragastric administration of BPA at the doses of 0, 2.5, 5, 10, 20, and 40 mg/kg/day at gestation day (GD) 0.5–17.5. The testis index of the offspring mice was calculated at postnatal day (PND) 21 and PND 56. The results showed that maternal exposure to 20 mg/kg BPA during pregnancy significantly increased the testicular index of F1 males at PND 21, and 40 mg/kg BPA significantly decreased the testicular index of F1 males at PND 56 (P < 0.01). BPA significantly reduced serum testosterone (T) and estradiol (E2) levels, and improved testicular ERα and ERβ levels in F1 males at both PND 21 and PND 56. BPA exposure also upregulated transcription of testicular Dnmt1 and inhibited the transcription of testicular Dnmt3A and Dnmt3B in F1 mice at PND 21. BPA reduced the transcriptional level of testicular DNA methyltransferase (Dnmt), increased the expression of testicular caspase-7, caspase-9, and bax, and decreased the expression of bcl-2 in F1 mice at PND 56. Consistent with that, BPA improved the apoptosis rate in the testis at PND 56 (P < 0.01 or P < 0.05). Our study indicates that BPA disrupts the secretion of testosterone, estradiol, and estrogen receptors by interfering with the transcription of testicular DNA methyltransferase (Dnmt) in offspring males, which damages testicular tissues and affects the potential reproductive function.
KeywordsBisphenol A Male offspring Reproduction DNA methyltransferase Apoptosis
This study was financially supported by the National Natural Science Foundation of China (no.31872506).
Compliance with ethical standards
The protocols using animals in our study were approved by the Council for Animal Care in Hebei province.
Conflict of interest
The authors declare that they have no conflicts of interest.
- Abilmona SM, Sumrell RM, Gill RS, Adler RA, Gorgey AS (2018) Serum testosterone levels may influence body composition and cardiometabolic health in men with spinal cord injury. Spinal Cord 57:229–239.Google Scholar
- Canovas S, Ross PJ, Kelsey G, Coy P (2017) DNA methylation in embryo development: epigenetic impact of ART (assisted reproductive technologies). Bioessays 39:1700106.Google Scholar
- D'Errico F, Goverse G, Dai Y, Wu W, Stakenborg M, Labeeuw E, De Simone V, Verstockt B, Gomez-Pinilla PJ, Warner M, Di Leo A, Matteoli G, Gustafsson JA (2018) Estrogen receptor beta controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage. Proc Natl Acad Sci U S A 115:5798–5803CrossRefGoogle Scholar
- Jurek A, Leitner E (2018) Analytical determination of bisphenol A (BPA) and bisphenol analogues in paper products by LC-MS/MS. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 34:1225–1238Google Scholar
- Laing LV, Viana J, Dempster EL, Uren Webster TM, van Aerle R, Mill J, Santos EM (2018) Sex-specific transcription and DNA methylation profiles of reproductive and epigenetic associated genes in the gonads and livers of breeding zebrafish. Comp Biochem Physiol A Mol Integr Physiol 222:16–25CrossRefGoogle Scholar
- Li Y, Duan F, Zhou X, Pan H, Li R (2018) Differential responses of GC1 spermatogonia cells to high and low doses of bisphenol A. Mol Med Rep 18:3034–3040Google Scholar
- Ma S, Shi W, Wang X, Song P, Zhong X (2017) Bisphenol A exposure during pregnancy alters the mortality and levels of reproductive hormones and genes in offspring mice. Biomed Res Int 2017:3585809Google Scholar
- Meng Y, Lin R, Wu F, Sun Q, Jia L (2018) Decreased capacity for sperm production induced by perinatal bisphenol A exposure is associated with an increased inflammatory response in the offspring of C57BL/6 male mice. Int J Environ Res Public Health 15.pii: E2158.Google Scholar
- Owczarek K, Kubica P, Kudlak B, Rutkowska A, Konieczna A, Rachon D, Namiesnik J, Wasik A (2018) Determination of trace levels of eleven bisphenol A analogues in human blood serum by high performance liquid chromatography-tandem mass spectrometry. Sci Total Environ 628–629:1362–1368CrossRefGoogle Scholar
- Passouant-Fontaine T, Flandre C (1968) Influence of neonatal estrogens on testis development and compensating hypertrophy after hemicastration in rats. C R Seances Soc Biol Fil 162:2175–2178Google Scholar
- Toro-Velez AF, Madera-Parra CA, Pena-Varon MR, Lee WY, Bezares-Cruz JC, Walker WS, Cardenas-Henao H, Quesada-Calderon S, Garcia-Hernandez H, Lens PN (2016) BPA and NP removal from municipal wastewater by tropical horizontal subsurface constructed wetlands. Sci Total Environ 542:93–101CrossRefGoogle Scholar
- Wang DH, Hu JR, Wang LY, Hu YJ, Tan FQ, Zhou H, Shao JZ, Yang WX (2012) The apoptotic function analysis of p53, Apaf1, Caspase3 and Caspase7 during the spermatogenesis of the Chinese fire-bellied newt Cynops orientalis. PLoS One 7:e39920. Google Scholar