Association of aberrant expression of sex-determining gene fibroblast growth factor 9 with Sertoli cell-only syndrome

Abstract

Objective: To investigate the expressions of fibroblast growth factor 9 (FGF9) in normal testes and in testes with Sertoli cell-only syndrome (SCOS), explore the biological function of testicular FGF9, and identify the sequence variants of FGF9 gene in patients with SCOS.

Design: Retrospective case study.

Setting: University reproductive clinic.

Patient(s): Forty-one patients with SCOS, seven with normal spermatogenesis, and 100 controls.

Intervention(s): Protein expressions of testicular FGF9 and sequence variants of FGF9 gene in normal controls and patients with SCOS were studied. The biological function and regulation of testicular FGF9 were assessed in vitro.

Main outcome measure(s): Expression profiles of testicular FGF9, effects of FGF9 on germ cell proliferation, and sequence variants of the FGF9 gene.

Result(s): FGF9 was predominately expressed in the cytoplasm of Leydig cells of normal testis; its expression was significantly decreased in patients with SCOS. Conditioned medium of FGF9-treated Leydig cells stimulated germ cell proliferation. A promoter polymorphism (c.-712C→T) of the FGF9 gene attenuated the promoter activity, which contributes to one of the causes of its low expression.

Conclusion(s): In addition to the role of sex determination, FGF9 is expressed in postnatal Leydig cells and is involved in cell-to-cell interaction of testicular function. Aberrant expression of testicular FGF9 is associated with SCOS.

Keywords: FGF9; Leydig cell; Sertoli cell–only syndrome; male infertility; polymorphism.