title: Aberrant DNA methylation at Igf2-H19 imprinting control region in spermatozoa upon neonatal exposure to bisphenol A and its association with post implantation loss.
abstract: Bisphenol A (BPA) is an estrogenic compound commonly used in manufacture of various consumer products. Earlier studies from our group have demonstrated that neonatal exposure of male rats to BPA causes decrease in sperm count and motility, increase in post implantation loss, ultimately leading to subfertility during adulthood. One of the factors contributing for post implantation loss is altered methylation pattern of imprinted genes. The present study was undertaken to investigate the molecular effects of neonatal exposure of male rats to BPA (2.4 μg/pup) (F0) on the methylation of H19 imprinting control region (ICR) in resorbed embryo (F1) and compared with spermatozoa of their respective sires (F0). We observed a significant down regulation in the transcript expression of Igf2 and H19 genes in BPA resorbed embryo (F1) as compared to control viable embryo. A significant hypomethylation was observed at the H19 ICR in the spermatozoa as well as in resorbed embryo sired by rats exposed neonatally to BPA. These results indicated that the aberrant methylation at ICR in spermatozoa was inherited by embryo which causes perturbation in the expression of Igf2 and H19, ultimately leading to post implantation loss. This could be one of the possible mechanisms of BPA induced adverse epigenetic effects on male fertility.
authors: National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, 400012, Maharashtra, India.
authors: Tanvi
authors: T
authors: Doshi
authors: Criselle
authors: C
authors: D'souza
authors: Geeta
authors: G
authors: Vanage
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D003001:Cloning, Molecular; D019175:DNA Methylation / Q000187:drug effects*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D020964:Embryo Loss / Q000139:chemically induced*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007279:Injections, Subcutaneous; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013094:Spermatozoa / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D017931:DNA Primers; D018076:DNA, Complementary; D007335:Insulin-Like Growth Factor II; D010636:Phenols; D062085:RNA, Long Noncoding; C094335:H19 long non-coding RNA; C006780:bisphenol A; D000098826:Bisphenol A Compounds
references: Environ Health Perspect. 2010 Aug;118(8):1055-70
references: 20338858
references: Genes Dev. 2009 Sep 15;23(18):2124-33
references: 19759261
references: Cell. 1991 Feb 22;64(4):849-59
references: 1997210
references: Mutat Res. 2011 May-Jun;727(3):62-71
references: 21540125
references: Reprod Toxicol. 2004 Dec;19(2):181-8
references: 15501383
references: Science. 2005 Jun 3;308(5727):1466-9
references: 15933200
references: Mol Hum Reprod. 2008 Feb;14(2):67-74
references: 18178607
references: Biol Reprod. 1998 Nov;59(5):1084-94
references: 9780313
references: Clin Chem. 2009 Apr;55(4):611-22
references: 19246619
references: Nat Rev Genet. 2002 Sep;3(9):662-73
references: 12209141
references: Toxicol Ind Health. 1998 Jan-Apr;14(1-2):239-60
references: 9460178
references: Dev Biol. 2002 Jan 1;241(1):172-82
references: 11784103
references: Biol Reprod. 2003 Jun;68(6):2081-91
references: 12606459
references: Fertil Steril. 2011 Feb;95(2):625-30.e1-4
references: 21035116
references: Cell. 1993 Oct 8;75(1):73-82
references: 8402902
references: Biochem Biophys Res Commun. 2006 Feb 3;340(1):83-9
references: 16359639
references: Blood. 1999 Jun 15;93(12):4059-70
references: 10361102
references: Environ Mol Mutagen. 2008 Jan;49(1):4-8
references: 18172876
references: FASEB J. 2010 Jul;24(7):2273-80
references: 20181937
references: Toxicology. 2011 Nov 18;289(2-3):74-82
references: 21827818
references: Eur J Hum Genet. 2009 Dec;17(12):1582-91
references: 19471309
references: Cancer Res. 2006 Jun 1;66(11):5624-32
references: 16740699
references: Reprod Toxicol. 2007 Aug-Sep;24(2):139-77
references: 17825522
references: Nat Genet. 2007 Mar;39(3):289-90
references: 17325677
references: Cell. 1999 Oct 29;99(3):247-57
references: 10555141
references: Biol Reprod. 2001 Oct;65(4):1215-23
references: 11566746
references: Reprod Toxicol. 2008 Feb;25(2):169-76
references: 18295446
references: Hum Mol Genet. 2007 Nov 1;16(21):2542-51
references: 17636251
references: Cytogenet Genome Res. 2006;113(1-4):122-9
references: 16575171
references: Environ Health Perspect. 2005 Aug;113(8):926-33
references: 16079060
references: Dev Biol. 2006 Jan 1;289(1):195-205
references: 16325170
references: Histochem Cell Biol. 2012 Feb;137(2):249-59
references: 22131059
references: Fertil Steril. 2009 May;91(5 Suppl):2253-63
references: 18778817
references: Reprod Fertil Dev. 2010;22(6):939-48
references: 20591328
references: Biochem Biophys Res Commun. 2008 Nov 21;376(3):563-7
references: 18804091
references: Mol Cell Biol. 2001 Dec;21(23):8189-96
references: 11689707
references: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13056-61
references: 17670942
references: Environ Health Perspect. 1995 Jun;103(6):608-12
references: 7556016
references: Environ Health Perspect. 1996 Mar;104(3):298-305
references: 8919768
references: Toxicology. 2009 Nov 9;265(1-2):56-67
references: 19782717
references: J Biochem Mol Toxicol. 2012 Sep;26(9):337-43
references: 22730197
references: Mol Cancer Res. 2006 Apr;4(4):283-92
references: 16603642
references: Mol Cell Endocrinol. 2010 Jan 15;314(1):110-7
references: 19683557
references: Cell Tissue Res. 2004 Jan;315(1):119-24
references: 14557871
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: J Clin Endocrinol Metab. 2011 Mar;96(3):E480-4
references: 21193545
references: Endocrinology. 2000 Sep;141(9):3235-44
references: 10965894
references: Curr Biol. 2003 Jul 1;13(13):1116-21
references: 12842010
references: Hum Reprod. 2005 Aug;20(8):2325-9
references: 15947000