Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads, whose ablation causes male infertility. Herein, we have investigated Sam68 expression in the adult ovary and its function in female fertility. Immunohistochemistry showed that Sam68 was localized in the nucleus of oocytes and follicular cells at all stages of folliculogenesis. Sam68(-/-) females were severely subfertile, and they showed a delay in the age of first pregnancy, increased breeding time for successful pregnancy and yielded smaller litters. Morphological analyses indicated a significant reduction in the number of secondary and pre-antral follicles in the ovary. These defects were associated with alteration of oestrous cycles and a reduced number of ovulated oocytes, which were only partially restored by the administration of exogenous gonadotropins. Crosslinking/immunoprecipitation experiments showed that Sam68 directly binds the mRNAs for the follicle-stimulating hormone (FSH) and the luteinizing hormone receptors (Fshr and Lhcgr), which were downregulated in ovaries of adult knockout females. Stimulation of immature females with FSH-like pregnant mare serum gonadotropin (PMSG), or of follicular cells with the FSH second messenger analogue 8Br-cAMP, caused the upregulation of Sam68. The increase in Sam68 levels paralleled that of the Fshr and Lhcgr mRNAs in the pre-ovulatory follicle and was required to allow accumulation of these transcripts in follicular cells. These studies identify a new crucial function for Sam68 in the regulation of female fertility and indicate that this protein is required to insure proper expression of the gonadotropin receptor transcripts in pre-ovulatory follicles in adult ovary.

Bianchi, E., Barbagallo, F., Valeri, C., Geremia, R., Salustri, A., DE FELICI, M., et al. (2010). Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. HUMAN MOLECULAR GENETICS, 19(24), 4886-4894 [10.1093/hmg/ddq422].

Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development

GEREMIA, RAFFAELE;SALUSTRI, ANTONIETTA;DE FELICI, MASSIMO;SETTE, CLAUDIO
2010

Abstract

Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads, whose ablation causes male infertility. Herein, we have investigated Sam68 expression in the adult ovary and its function in female fertility. Immunohistochemistry showed that Sam68 was localized in the nucleus of oocytes and follicular cells at all stages of folliculogenesis. Sam68(-/-) females were severely subfertile, and they showed a delay in the age of first pregnancy, increased breeding time for successful pregnancy and yielded smaller litters. Morphological analyses indicated a significant reduction in the number of secondary and pre-antral follicles in the ovary. These defects were associated with alteration of oestrous cycles and a reduced number of ovulated oocytes, which were only partially restored by the administration of exogenous gonadotropins. Crosslinking/immunoprecipitation experiments showed that Sam68 directly binds the mRNAs for the follicle-stimulating hormone (FSH) and the luteinizing hormone receptors (Fshr and Lhcgr), which were downregulated in ovaries of adult knockout females. Stimulation of immature females with FSH-like pregnant mare serum gonadotropin (PMSG), or of follicular cells with the FSH second messenger analogue 8Br-cAMP, caused the upregulation of Sam68. The increase in Sam68 levels paralleled that of the Fshr and Lhcgr mRNAs in the pre-ovulatory follicle and was required to allow accumulation of these transcripts in follicular cells. These studies identify a new crucial function for Sam68 in the regulation of female fertility and indicate that this protein is required to insure proper expression of the gonadotropin receptor transcripts in pre-ovulatory follicles in adult ovary.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16
English
Con Impact Factor ISI
Gonadotropins, equine; male; infertility, female; female; animals; rna, messenger; adaptor proteins, signal transducing; receptors, gonadotropin; up-regulation; gene expression regulation, developmental; mice; pregnancy; gene deletion; ovarian follicle; rna-binding proteins; protein binding; estrous cycle
Bianchi, E., Barbagallo, F., Valeri, C., Geremia, R., Salustri, A., DE FELICI, M., et al. (2010). Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. HUMAN MOLECULAR GENETICS, 19(24), 4886-4894 [10.1093/hmg/ddq422].
Bianchi, E; Barbagallo, F; Valeri, C; Geremia, R; Salustri, A; DE FELICI, M; Sette, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/22919
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