BACKGROUND: Bisphenol A (BPA) is an estrogenic endocrine disruptor commonly used in manufacture of polycarbonate plastics and epoxy resins. Due to its ubiquitous presence in the environment, health concerns are increasing. Earlier studies from our group have shown that neonatal exposure of male rats to BPA affected spermatogenesis leading to impairment in fertility during adulthood. Further we also observed an altered gene expression of ERα and ERβ in adult testis upon BPA exposure. Based on these results, we hypothesized that apart from endocrine action, BPA might mediate perturbations in expression of ERs via epigenetic mechanism. OBJECTIVES: The present study was undertaken to determine the effect of exposure of neonatal male rats to BPA on DNA methylation profile of estrogen receptor promoter region and on DNA methylation machinery. METHODS: In order to test this hypothesis, neonatal male rats were subcutaneously injected with 2.4μg of BPA/day for the first five days of life, i.e., on postnatal days (PND) 1-5, while control group received vehicle (sesame oil). Animals were sacrificed during adulthood (PND-125) and testes were dissected out for analysis. Methylation pattern of promoter region of ERα and ERβ was analyzed in the testis by bisulfite sequencing and expression levels of DNA methyltransferases by quantitative RT-PCR and Western blotting respectively. RESULTS: Bisulfite sequencing revealed significant hypermethylation of ERα promoter to varying extents from 40% to 60%, and ERβ promoter region with varying extent from 20% to 65%. Approximately 2-fold increase in Dnmt3a and Dnmt3b expression at transcript and protein level was also observed. CONCLUSION: The experimental evidence demonstrated that the neonatal exposure of rats to BPA led to aberrant DNA methylation in testis, indicating methylation mediated epigenetic changes as one of the possible mechanisms of BPA induced adverse effects on spermatogenesis and fertility.
BACKGROUND:Bisphenol A (BPA) is an estrogenic endocrine disruptor commonly used in manufacture of polycarbonate plastics and epoxy resins. Due to its ubiquitous presence in the environment, health concerns are increasing. Earlier studies from our group have shown that neonatal exposure of male rats to BPA affected spermatogenesis leading to impairment in fertility during adulthood. Further we also observed an altered gene expression of ERα and ERβ in adult testis upon BPA exposure. Based on these results, we hypothesized that apart from endocrine action, BPA might mediate perturbations in expression of ERs via epigenetic mechanism. OBJECTIVES: The present study was undertaken to determine the effect of exposure of neonatal male rats to BPA on DNA methylation profile of estrogen receptor promoter region and on DNA methylation machinery. METHODS: In order to test this hypothesis, neonatal male rats were subcutaneously injected with 2.4μg of BPA/day for the first five days of life, i.e., on postnatal days (PND) 1-5, while control group received vehicle (sesame oil). Animals were sacrificed during adulthood (PND-125) and testes were dissected out for analysis. Methylation pattern of promoter region of ERα and ERβ was analyzed in the testis by bisulfite sequencing and expression levels of DNA methyltransferases by quantitative RT-PCR and Western blotting respectively. RESULTS:Bisulfite sequencing revealed significant hypermethylation of ERα promoter to varying extents from 40% to 60%, and ERβ promoter region with varying extent from 20% to 65%. Approximately 2-fold increase in Dnmt3a and Dnmt3b expression at transcript and protein level was also observed. CONCLUSION: The experimental evidence demonstrated that the neonatal exposure of rats to BPA led to aberrant DNA methylation in testis, indicating methylation mediated epigenetic changes as one of the possible mechanisms of BPA induced adverse effects on spermatogenesis and fertility.
Authors: Sabine A S Langie; Gudrun Koppen; Daniel Desaulniers; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Amaya Azqueta; William H Bisson; Dustin G Brown; Gunnar Brunborg; Amelia K Charles; Tao Chen; Annamaria Colacci; Firouz Darroudi; Stefano Forte; Laetitia Gonzalez; Roslida A Hamid; Lisbeth E Knudsen; Luc Leyns; Adela Lopez de Cerain Salsamendi; Lorenzo Memeo; Chiara Mondello; Carmel Mothersill; Ann-Karin Olsen; Sofia Pavanello; Jayadev Raju; Emilio Rojas; Rabindra Roy; Elizabeth P Ryan; Patricia Ostrosky-Wegman; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Frederik J Van Schooten; Mahara Valverde; Jordan Woodrick; Luoping Zhang; Nik van Larebeke; Micheline Kirsch-Volders; Andrew R Collins Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: E O'Brien; I L Bergin; D C Dolinoy; Z Zaslona; R J A Little; Y Tao; M Peters-Golden; P Mancuso Journal: J Dev Orig Health Dis Date: 2014-04 Impact factor: 2.401
Authors: William H Goodson; Leroy Lowe; David O Carpenter; Michael Gilbertson; Abdul Manaf Ali; Adela Lopez de Cerain Salsamendi; Ahmed Lasfar; Amancio Carnero; Amaya Azqueta; Amedeo Amedei; Amelia K Charles; Andrew R Collins; Andrew Ward; Anna C Salzberg; Annamaria Colacci; Ann-Karin Olsen; Arthur Berg; Barry J Barclay; Binhua P Zhou; Carmen Blanco-Aparicio; Carolyn J Baglole; Chenfang Dong; Chiara Mondello; Chia-Wen Hsu; Christian C Naus; Clement Yedjou; Colleen S Curran; Dale W Laird; Daniel C Koch; Danielle J Carlin; Dean W Felsher; Debasish Roy; Dustin G Brown; Edward Ratovitski; Elizabeth P Ryan; Emanuela Corsini; Emilio Rojas; Eun-Yi Moon; Ezio Laconi; Fabio Marongiu; Fahd Al-Mulla; Ferdinando Chiaradonna; Firouz Darroudi; Francis L Martin; Frederik J Van Schooten; Gary S Goldberg; Gerard Wagemaker; Gladys N Nangami; Gloria M Calaf; Graeme Williams; Gregory T Wolf; Gudrun Koppen; Gunnar Brunborg; H Kim Lyerly; Harini Krishnan; Hasiah Ab Hamid; Hemad Yasaei; Hideko Sone; Hiroshi Kondoh; Hosni K Salem; Hsue-Yin Hsu; Hyun Ho Park; Igor Koturbash; Isabelle R Miousse; A Ivana Scovassi; James E Klaunig; Jan Vondráček; Jayadev Raju; Jesse Roman; John Pierce Wise; Jonathan R Whitfield; Jordan Woodrick; Joseph A Christopher; Josiah Ochieng; Juan Fernando Martinez-Leal; Judith Weisz; Julia Kravchenko; Jun Sun; Kalan R Prudhomme; Kannan Badri Narayanan; Karine A Cohen-Solal; Kim Moorwood; Laetitia Gonzalez; Laura Soucek; Le Jian; Leandro S D'Abronzo; Liang-Tzung Lin; Lin Li; Linda Gulliver; Lisa J McCawley; Lorenzo Memeo; Louis Vermeulen; Luc Leyns; Luoping Zhang; Mahara Valverde; Mahin Khatami; Maria Fiammetta Romano; Marion Chapellier; Marc A Williams; Mark Wade; Masoud H Manjili; Matilde E Lleonart; Menghang Xia; Michael J Gonzalez; Michalis V Karamouzis; Micheline Kirsch-Volders; Monica Vaccari; Nancy B Kuemmerle; Neetu Singh; Nichola Cruickshanks; Nicole Kleinstreuer; Nik van Larebeke; Nuzhat Ahmed; Olugbemiga Ogunkua; P K Krishnakumar; Pankaj Vadgama; Paola A Marignani; Paramita M Ghosh; Patricia Ostrosky-Wegman; Patricia A Thompson; Paul Dent; Petr Heneberg; Philippa Darbre; Po Sing Leung; Pratima Nangia-Makker; Qiang Shawn Cheng; R Brooks Robey; Rabeah Al-Temaimi; Rabindra Roy; Rafaela Andrade-Vieira; Ranjeet K Sinha; Rekha Mehta; Renza Vento; Riccardo Di Fiore; Richard Ponce-Cusi; Rita Dornetshuber-Fleiss; Rita Nahta; Robert C Castellino; Roberta Palorini; Roslida Abd Hamid; Sabine A S Langie; Sakina E Eltom; Samira A Brooks; Sandra Ryeom; Sandra S Wise; Sarah N Bay; Shelley A Harris; Silvana Papagerakis; Simona Romano; Sofia Pavanello; Staffan Eriksson; Stefano Forte; Stephanie C Casey; Sudjit Luanpitpong; Tae-Jin Lee; Takemi Otsuki; Tao Chen; Thierry Massfelder; Thomas Sanderson; Tiziana Guarnieri; Tove Hultman; Valérian Dormoy; Valerie Odero-Marah; Venkata Sabbisetti; Veronique Maguer-Satta; W Kimryn Rathmell; Wilhelm Engström; William K Decker; William H Bisson; Yon Rojanasakul; Yunus Luqmani; Zhenbang Chen; Zhiwei Hu Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Jung H Kim; Maureen A Sartor; Laura S Rozek; Christopher Faulk; Olivia S Anderson; Tamara R Jones; Muna S Nahar; Dana C Dolinoy Journal: BMC Genomics Date: 2014-01-17 Impact factor: 3.969
Authors: Marija Kundakovic; Kathryn Gudsnuk; Becca Franks; Jesus Madrid; Rachel L Miller; Frederica P Perera; Frances A Champagne Journal: Proc Natl Acad Sci U S A Date: 2013-05-28 Impact factor: 11.205