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Maternal exposure to bisphenol A during pregnancy interferes testis development of F1 male mice

  • Yuanyuan Wei
  • Chao Han
  • Yumeng Geng
  • Yuqing Cui
  • Yongzhan Bao
  • Wanyu ShiEmail author
  • Xiuhui ZhongEmail author
Research Article

Abstract

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.

Keywords

Bisphenol A Male offspring Reproduction DNA methyltransferase Apoptosis 

Notes

Funding information

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.

References

  1. Abbasi J (2018) Scientists call FDA statement on bisphenol a safety premature. JAMA 319:1644–1646CrossRefGoogle Scholar
  2. 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
  3. Armstrong CM, Allred KF, Weeks BR, Chapkin RS, Allred CD (2017) Estradiol has differential effects on acute colonic inflammation in the presence and absence of estrogen receptor beta expression. Dig Dis Sci 62:1977–1984CrossRefGoogle Scholar
  4. Banerjee A, Anjum S, Verma R, Krishna A (2012) Alteration in expression of estrogen receptor isoforms alpha and beta, and aromatase in the testis and its relation with changes in nitric oxide during aging in mice. Steroids 77:609–620CrossRefGoogle Scholar
  5. Beal JA (2018) Baby bottles and bisphenol A (BPA): still a parental concern. MCN Am J Matern Child Nurs 43:349CrossRefGoogle Scholar
  6. 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
  7. Comeglio P, Cellai I, Filippi S, Corno C, Corcetto F, Morelli A, Maneschi E, Maseroli E, Mannucci E, Fambrini M, Maggi M, Vignozzi L (2016) Differential effects of testosterone and estradiol on clitoral function: an experimental study in rats. J Sex Med 13:1858–1871CrossRefGoogle Scholar
  8. Delbes G, Levacher C, Pairault C, Racine C, Duquenne C, Krust A, Habert R (2004) Estrogen receptor beta-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life. Endocrinology 145:3395–3403CrossRefGoogle Scholar
  9. 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
  10. Fagin D (2012) Toxicology: the learning curve. Nature 490:462–465CrossRefGoogle Scholar
  11. Fenichel P, Chevalier N (2017) Environmental endocrine disruptors: new diabetogens? C R Biol 340:446–452CrossRefGoogle Scholar
  12. Gupta S, Guha P, Majumder S, Pal P, Sen K, Chowdhury P, Chakraborty A, Panigrahi AK, Mukherjee D (2018) Effects of bisphenol A (BPA) on brain-specific expression of cyp19a1b gene in swim-up fry of Labeo rohita. Comp Biochem Physiol C Toxicol Pharmacol 209:63–71CrossRefGoogle Scholar
  13. Huang YQ, Wong CK, Zheng JS, Bouwman H, Barra R, Wahlstrom B, Neretin L, Wong MH (2012) Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. Environ Int 42:91–99CrossRefGoogle Scholar
  14. Imao M, Nagaki M, Imose M, Moriwaki H (2006) Differential caspase-9-dependent signaling pathway between tumor necrosis factor receptor- and Fas-mediated hepatocyte apoptosis in mice. Liver Int 26:137–146CrossRefGoogle Scholar
  15. Ji Y, Hu B, Li J, Traub RJ (2018) Opposing roles of estradiol and testosterone on stress-induced visceral hypersensitivity in rats. J Pain 19:764–776CrossRefGoogle Scholar
  16. Jiang X, Yin L, Zhang N, Han F, Liu WB, Zhang X, Chen HQ, Cao J, Liu JY (2018) Bisphenol A induced male germ cell apoptosis via IFNbeta-XAF1-XIAP pathway in adult mice. Toxicol Appl Pharmacol 355:247–256CrossRefGoogle Scholar
  17. Jin H, Zhu L (2016) Occurrence and partitioning of bisphenol analogues in water and sediment from Liaohe River Basin and Taihu Lake, China. Water Res 103:343–351CrossRefGoogle Scholar
  18. 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
  19. Kundakovic M, Champagne FA (2011) Epigenetic perspective on the developmental effects of bisphenol A. Brain Behav Immun 25:1084–1093CrossRefGoogle Scholar
  20. 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
  21. 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
  22. 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
  23. 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
  24. Muhamad MS, Salim MR, Lau WJ, Yusop Z (2016) A review on bisphenol A occurrences, health effects and treatment process via membrane technology for drinking water. Environ Sci Pollut Res Int 23:11549–11567CrossRefGoogle Scholar
  25. Negev M, Berman T, Reicher S, Balan S, Soehl A, Goulden S, Ardi R, Shammai Y, Hadar L, Blum A, Diamond ML (2018) Regulation of chemicals in children’s products: how U.S. and EU regulation impacts small markets. Sci Total Environ 616-617:462–471CrossRefGoogle Scholar
  26. 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
  27. 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
  28. Petrie B, Lopardo L, Proctor K, Youdan J, Barden R, Kasprzyk-Hordern B (2019) Assessment of bisphenol-A in the urban water cycle. Sci Total Environ 650:900–907CrossRefGoogle Scholar
  29. Pirard C, Compere S, Firquet K, Charlier C (2018) The current environmental levels of endocrine disruptors (mercury, cadmium, organochlorine pesticides and PCBs) in a Belgian adult population and their predictors of exposure. Int J Hyg Environ Health 221:211–222CrossRefGoogle Scholar
  30. Potter C, McKay J, Groom A, Ford D, Coneyworth L, Mathers JC, Relton CL (2013) Influence of DNMT genotype on global and site specific DNA methylation patterns in neonates and pregnant women. PLoS One 8:e76506CrossRefGoogle Scholar
  31. Quan C, Wang C, Duan P, Huang W, Yang K (2017) Prenatal bisphenol a exposure leads to reproductive hazards on male offspring via the Akt/mTOR and mitochondrial apoptosis pathways. Environ Toxicol 32:1007–1023CrossRefGoogle Scholar
  32. Rahmani S, Pour Khalili N, Khan F, Hassani S, Ghafour-Boroujerdi E, Abdollahi M (2018) Bisphenol A: what lies beneath its induced diabetes and the epigenetic modulation? Life Sci 214:136–144CrossRefGoogle Scholar
  33. Ricci PF (2015) Endocrine disruptors: improving regulatory science policy. Dose-Response 13:1559325815611903CrossRefGoogle Scholar
  34. Robinson JL, Gupta V, Soria P, Clanaman E, Gurbarg S, Xu M, Chen J, Wadhwa S (2017) Estrogen receptor alpha mediates mandibular condylar cartilage growth in male mice. Orthod Craniofacial Res 20(Suppl 1):167–171CrossRefGoogle Scholar
  35. Roset R, Ortet L, Gil-Gomez G (2007) Role of Bcl-2 family members on apoptosis: what we have learned from knock-out mice. Front Biosci 12:4722–4730CrossRefGoogle Scholar
  36. Sano K, Morimoto C, Nataka M, Musatov S, Tsuda MC, Yamaguchi N, Sakamoto T, Ogawa S (2018) The role of estrogen receptor beta in the dorsal raphe nucleus on the expression of female sexual behavior in C57BL/6J mice. Front Endocrinol (Lausanne) 9:243CrossRefGoogle Scholar
  37. Takahashi O, Oishi S (2006) Male reproductive toxicity of four bisphenol antioxidants in mice and rats and their estrogenic effect. Arch Toxicol 80:225–241CrossRefGoogle Scholar
  38. 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
  39. Urriola-Munoz P, Lagos-Cabre R, Moreno RD (2014) A mechanism of male germ cell apoptosis induced by bisphenol-A and nonylphenol involving ADAM17 and p38 MAPK activation. PLoS One 9:e113793CrossRefGoogle Scholar
  40. Vasquez YM (2018) Estrogen-regulated transcription: mammary gland and uterus. Steroids 133:82–86CrossRefGoogle Scholar
  41. 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
  42. Wei Q, Luo Q, Liu H, Chen L, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L (2018) The mitochondrial pathway is involved in sodium fluoride (NaF)-induced renal apoptosis in mice. Toxicol Res (Camb) 7:792–808CrossRefGoogle Scholar
  43. Wirbisky-Hershberger SE, Sanchez OF, Horzmann KA, Thanki D, Yuan C, Freeman JL (2017) Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression. Food Chem Toxicol 109:727–734CrossRefGoogle Scholar
  44. Xia W, Jiang Y, Li Y, Wan Y, Liu J, Ma Y, Mao Z, Chang H, Li G, Xu B, Chen X, Xu S (2014) Early-life exposure to bisphenol a induces liver injury in rats involvement of mitochondria-mediated apoptosis. PLoS One 9:e90443CrossRefGoogle Scholar
  45. Xu W, Guo G, Li J, Ding Z, Sheng J, Li J, Tan W (2016) Activation of Bcl-2-Caspase-9 apoptosis pathway in the testis of asthmatic mice. PLoS One 11:e0149353CrossRefGoogle Scholar
  46. Xue J, Venkatesan AK, Wu Q, Halden RU, Kannan K (2015) Occurrence of bisphenol A Diglycidyl ethers (BADGEs) and Novolac Glycidyl ethers (NOGEs) in archived biosolids from the U.S. EPA’s targeted National Sewage Sludge Survey. Environ Sci Technol 49:6538–6544CrossRefGoogle Scholar
  47. Ye Y, Tang Y, Xiong Y, Feng L, Li X (2019) Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2. FASEB J 33:2732–2742CrossRefGoogle Scholar
  48. Yin C, Kang L, Lai C, Zhou J, Shi B, Zhang L, Chen H (2017) Effects of 17beta-estradiol on leptin signaling in anterior pituitary of ovariectomized rats. Exp Anim 66:159–166CrossRefGoogle Scholar
  49. Zhang S, Tang B, Fan C, Shi L, Zhang X, Sun L, Li Z (2015) Effect of DNMT inhibitor on bovine parthenogenetic embryo development. Biochem Biophys Res Commun 466:505–511CrossRefGoogle Scholar
  50. Zhang W, Schmull S, Du M, Liu J, Lu Z, Zhu H, Xue S, Lian F (2016) Estrogen receptor alpha and beta in mouse: adipose-derived stem cell proliferation, migration, and brown adipogenesis in vitro. Cell Physiol Biochem 38:2285–2299CrossRefGoogle Scholar
  51. Zhang Y, Han L, Yang H, Pang J, Li P, Zhang G, Li F, Wang F (2017) Bisphenol A affects cell viability involved in autophagy and apoptosis in goat testis sertoli cell. Environ Toxicol Pharmacol 55:137–147CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Traditional Chinese Veterinary MedicineAgricultural University of HebeiBaodingChina

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