title: Estrogen signaling, through estrogen receptor β, regulates DNA methylation and its machinery in male germ line in adult rats.
abstract: Estrogen, through its receptors, regulates various aspects of spermatogenesis and male fertility. To understand the roles of estrogen receptors (ERα and ERβ) in male fertility, we have developed in vivo selective ER agonist administration models. Treatment of adult male rats with ERα or ERβ agonist for 60 d decreases fertility and litter size mainly due to increased pre- and post-implantation embryo loss. Since epigenetic mechanisms like DNA methylation play a crucial role in male fertility, we investigated the effects of the ER agonists on DNA methylation in spermatozoa. Treatment with ERβ agonist causes a significant decrease in DNA methylation both at the global level and at the H19 differentially methylated region (DMR). This could be due to decrease in DNA methyltransferases in the testis upon ERβ agonist treatment. The hypomethylation observed at the H19 DMR corroborates with aberrant expression of Igf2 and H19 imprinted genes in the resorbed embryos sired by ERβ agonist-treated males. Thus, our study demonstrates that ERβ regulates DNA methylation and methylating enzymes during adult rat spermatogenesis. Activation of estrogen signaling through ERβ could therefore cause DNA methylation defects leading to impaired male fertility. These results define a role for estrogen in epigenetic regulation of male germ line, suggesting that epigenetic insults by exposure to environmental estrogens could potentially affect male fertility.
authors.affiliation: a Department of Neuroendocrinology , National Institute for Research in Reproductive Health (Indian Council of Medical Research) , Parel, Mumbai , India.
authors.forename: Kushaan
authors.initials: K
authors.lastname: Dumasia
authors.affiliation: a Department of Neuroendocrinology , National Institute for Research in Reproductive Health (Indian Council of Medical Research) , Parel, Mumbai , India.
authors.forename: Anita
authors.initials: A
authors.lastname: Kumar
authors.affiliation: a Department of Neuroendocrinology , National Institute for Research in Reproductive Health (Indian Council of Medical Research) , Parel, Mumbai , India.
authors.forename: Sharvari
authors.initials: S
authors.lastname: Deshpande
authors.affiliation: a Department of Neuroendocrinology , National Institute for Research in Reproductive Health (Indian Council of Medical Research) , Parel, Mumbai , India.
authors.forename: Nafisa H
authors.initials: NH
authors.lastname: Balasinor
mesh_terms: D000328:Adult; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics; D005854:Germ Cells / Q000187:drug effects; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats; D015398:Signal Transduction; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics*; D013094:Spermatozoa / Q000187:drug effects / Q000254:growth & development
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C094335:H19 long non-coding RNA; C000599313:Igf2 protein, rat; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
keywords: DNA methylation; DNA methyltransferases; ERβ; estrogen; spermatozoa