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15 May 2013 Low 17beta-Estradiol Levels in Cnr1 Knock-Out Mice Affect Spermatid Chromatin Remodeling by Interfering with Chromatin Reorganization
Giovanna Cacciola, Teresa Chioccarelli, Lucia Altucci, Catherine Ledent, J. Ian Mason, Silvia Fasano, Riccardo Pierantoni, Gilda Cobellis
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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.

Giovanna Cacciola, Teresa Chioccarelli, Lucia Altucci, Catherine Ledent, J. Ian Mason, Silvia Fasano, Riccardo Pierantoni, and Gilda Cobellis "Low 17beta-Estradiol Levels in Cnr1 Knock-Out Mice Affect Spermatid Chromatin Remodeling by Interfering with Chromatin Reorganization," Biology of Reproduction 88(6), (15 May 2013). https://doi.org/10.1095/biolreprod.112.105726
Received: 22 October 2012; Accepted: 1 May 2013; Published: 15 May 2013
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KEYWORDS
cannabinoid receptor
chromatin remodeling
DNA damage
endocannabinoids
epigenetic
estrogens
FSH
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