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

Enrica Bianchi, Federica Barbagallo, Claudia Valeri, Raffaele Geremia, Antonietta Salustri, Massimo de Felici, Claudio Sette

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Article numberddq422
Pages (from-to)4886-4894
Number of pages9
JournalHuman Molecular Genetics
Volume19
Issue number24
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Gonadotropins
Fertility
Ovary
Follicle Stimulating Hormone
Genes
Oocytes
Gonadotropin Receptors
Equine Gonadotropins
LH Receptors
Pregnancy
Messenger RNA
RNA-Binding Proteins
Male Infertility
Gonads
Second Messenger Systems
Immunoprecipitation
Breeding
Up-Regulation
Down-Regulation
Immunohistochemistry

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Bianchi, E., Barbagallo, F., Valeri, C., Geremia, R., Salustri, A., de Felici, M., & Sette, C. (2010). Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. Human Molecular Genetics, 19(24), 4886-4894. [ddq422]. https://doi.org/10.1093/hmg/ddq422

Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. / Bianchi, Enrica; Barbagallo, Federica; Valeri, Claudia; Geremia, Raffaele; Salustri, Antonietta; de Felici, Massimo; Sette, Claudio.

In: Human Molecular Genetics, Vol. 19, No. 24, ddq422, 12.2010, p. 4886-4894.

Research output: Contribution to journalArticle

Bianchi, E, Barbagallo, F, Valeri, C, Geremia, R, Salustri, A, de Felici, M & Sette, C 2010, 'Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development', Human Molecular Genetics, vol. 19, no. 24, ddq422, pp. 4886-4894. https://doi.org/10.1093/hmg/ddq422
Bianchi E, Barbagallo F, Valeri C, Geremia R, Salustri A, de Felici M et al. Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. Human Molecular Genetics. 2010 Dec;19(24):4886-4894. ddq422. https://doi.org/10.1093/hmg/ddq422
Bianchi, Enrica ; Barbagallo, Federica ; Valeri, Claudia ; Geremia, Raffaele ; Salustri, Antonietta ; de Felici, Massimo ; Sette, Claudio. / Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 24. pp. 4886-4894.
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