title: Low 17beta-estradiol levels in CNR1 knock-out mice affect spermatid chromatin remodeling by interfering with chromatin reorganization.
abstract: The type 1-cannabinoid receptor, CNR1, regulates differentiation of spermatids. Indeed, we have recently reported that the genetic inactivation of Cnr1 in mice influenced chromatin remodeling of spermatids, by reducing histone displacement and then sperm chromatin quality indices (chromatin condensation and DNA integrity). Herein, we have studied, at both central and testicular levels, the molecular signals potentially involved in histone displacement. In particular, investigation of the neuroendocrine axis involved in estrogen production demonstrated down-regulation of the axis supporting FSH/estrogen secretion in Cnr1-knockout male mice. Conversely, Cnr1-knockout male mice treated with 17beta-estradiol showed a weak increase of pituitary Fsh-beta subunit mRNA levels and a rescue of sperm chromatin quality indices demonstrating that estrogens, possibly in combination with FSH secretion, play an important role in regulating chromatin remodeling of spermatids.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sez Bottazzi, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cacciola
authors.forename: Teresa
authors.initials: T
authors.lastname: Chioccarelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: J Ian
authors.initials: JI
authors.lastname: Mason
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pierantoni
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000097:blood* / Q000494:pharmacology; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D013087:Spermatids / Q000187:drug effects / Q000378:metabolism*; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000187:drug effects / Q000378:metabolism
chemical_list: C578453:CNR1 protein, mouse; D002843:Chromatin; D037201:Follicle Stimulating Hormone, beta Subunit; D043884:Receptor, Cannabinoid, CB1; D011962:Receptors, FSH; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D001141:Aromatase
keywords: DNA damage; FSH; GnRH; cannabinoid receptor; chromatin remodeling; endocannabinoids; epigenetic; estrogens; gonadotropins; hypothalamus; spermatids; spermatogenesis; spermiogenesis; testis