Glial cell line-derived neurotrophic factor (GDNF) and retinoic acid (RA) are two molecules crucial for the regulation of the spermatogonial compartment of the testis. During the cycle of the seminiferous epithelium, their relative concentration oscillates with lower GDNF levels in stages where RA levels are high. It has been recently shown that RA negatively regulates Gdnf expression but the mechanisms behind are so far unknown. Here, we show that RA directly downregulates Gdnf mRNA levels in primary murine Sertoli cells through binding of RARα to a novel DR5-RARE on Gdnf promoter. Pharmacological inhibition and chromatin immunoprecipitation–quantitative polymerase chain reaction analysis suggested that the underlying mechanism involved histone deacetylase activity and epigenetic repression of Gdnf promoter upon RA treatment.

Regulation of Gdnf expression by retinoic acid in Sertoli cells / Saracino, R.; Capponi, C.; Di Persio, S.; Boitani, C.; Masciarelli, S.; Fazi, F.; Fera, S.; Vicini, E.. - In: MOLECULAR REPRODUCTION AND DEVELOPMENT. - ISSN 1040-452X. - (2020), pp. 1-11. [10.1002/mrd.23323]

Regulation of Gdnf expression by retinoic acid in Sertoli cells

Saracino R.;Capponi C.;Di Persio S.;Boitani C.;Masciarelli S.;Fazi F.;Fera S.;Vicini E.
2020

Abstract

Glial cell line-derived neurotrophic factor (GDNF) and retinoic acid (RA) are two molecules crucial for the regulation of the spermatogonial compartment of the testis. During the cycle of the seminiferous epithelium, their relative concentration oscillates with lower GDNF levels in stages where RA levels are high. It has been recently shown that RA negatively regulates Gdnf expression but the mechanisms behind are so far unknown. Here, we show that RA directly downregulates Gdnf mRNA levels in primary murine Sertoli cells through binding of RARα to a novel DR5-RARE on Gdnf promoter. Pharmacological inhibition and chromatin immunoprecipitation–quantitative polymerase chain reaction analysis suggested that the underlying mechanism involved histone deacetylase activity and epigenetic repression of Gdnf promoter upon RA treatment.
2020
cycle of the seminiferous epithelium; GDNF; retinoic acid; Sertoli cells
01 Pubblicazione su rivista::01a Articolo in rivista
Regulation of Gdnf expression by retinoic acid in Sertoli cells / Saracino, R.; Capponi, C.; Di Persio, S.; Boitani, C.; Masciarelli, S.; Fazi, F.; Fera, S.; Vicini, E.. - In: MOLECULAR REPRODUCTION AND DEVELOPMENT. - ISSN 1040-452X. - (2020), pp. 1-11. [10.1002/mrd.23323]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1362942
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