title: Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis.
abstract: Estrogens, through their receptors, play an important role in regulation of spermatogenesis. However, the precise role of the estrogen receptors (ESR1 and ESR2) has been difficult to determine as in vivo estradiol treatment would signal through both the ESRs. Hence we had developed in vivo selective ESR agonist administration models in adult male rats to decipher the individual roles of the ESRs. Treatment with both ESR1 and ESR2 agonists decreased sperm counts after 60 days of treatment. The present study aimed to delineate the precise causes of decreased sperm counts following treatment with the two ESR agonists. Treatment with ESR1 agonist causes an arrest in differentiation of round spermatids into elongated spermatids, mainly due to down-regulation of genes involved in spermiogenesis. ESR2 agonist administration reduces sperm counts due to spermiation failure and spermatocyte apoptosis. Spermiation failure observed is due to defects in tubulobulbar complex formation because of decrease in expression of genes involved in actin remodelling. The increase in spermatocyte apoptosis could be due to increase in oxidative stress and decrease in transcripts of anti-apoptotic genes. Our results suggest that the two ESRs regulate distinct aspects of spermatogenesis. ESR1 is mainly involved with regulation of spermiogenesis, while ESR2 regulates spermatocyte apoptosis and spermiation. Activation of estrogen signaling through either of the receptors can affect their respective processes during spermatogenesis and lead to low sperm output. Since many environmental estrogens can bind to the two ESRs with different affinities, these observations can be useful in understanding their potential effects on spermatogenesis.
authors.affiliation: Department of Neuroendocrinology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai 400 012, India.
authors.forename: Kushaan
authors.initials: K
authors.lastname: Dumasia
authors.affiliation: Department of Neuroendocrinology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai 400 012, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Neuroendocrinology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai 400 012, India.
authors.forename: Sharvari
authors.initials: S
authors.lastname: Deshpande
authors.affiliation: Confocal Facility, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai 400 012, India.
authors.forename: Shobha
authors.initials: S
authors.lastname: Sonawane
authors.affiliation: Department of Neuroendocrinology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai 400 012, India. Electronic address: balasinorn@nirrh.res.in.
authors.forename: N H
authors.initials: NH
authors.lastname: Balasinor
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000166:cytology; D015398:Signal Transduction / Q000187:drug effects; D013087:Spermatids / Q000166:cytology / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics; D013737:Testis / Q000166:cytology; D013739:Testosterone / Q000378:metabolism; D011422:Propionates
chemical_list: D005640:Follicle Stimulating Hormone; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; D011960:Receptors, Estrogen; D013739:Testosterone; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
keywords: Estrogen receptors; Germ cell apoptosis; Spermatogenesis; Spermiation; Spermiogenesis