HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsEnrica Bianchi, Federica Barbagallo, Claudia Valeri, Raffaele Geremia, Antonietta Salustri, Massimo De Felici, Claudio Sette
JournalHuman molecular genetics (Hum Mol Genet) Vol. 19 Issue 24 Pg. 4886-94 (Dec 15 2010) ISSN: 1460-2083 [Electronic] England
PMID20881015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Gonadotropins, Equine
  • Khdrbs1 protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Gonadotropin
Topics
  • Adaptor Proteins, Signal Transducing (deficiency, genetics, metabolism)
  • Animals
  • Estrous Cycle (drug effects)
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Developmental (drug effects)
  • Gonadotropins, Equine (pharmacology)
  • Infertility, Female (genetics, pathology)
  • Male
  • Mice
  • Ovarian Follicle (drug effects, growth & development, pathology, physiopathology)
  • Pregnancy
  • Protein Binding (drug effects)
  • RNA, Messenger (genetics, metabolism)
  • RNA-Binding Proteins (genetics, metabolism)
  • Receptors, Gonadotropin (genetics, metabolism)
  • Up-Regulation (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: