Transforming growth factor-β1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction
Transforming growth factor-β1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction
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DOI：
10.1210/en.2006-1759
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发表时间：
2007-08-01
期刊：
影响因子：
4.8
通讯作者：
Robertson, Sarah A.
中科院分区：
文献类型：
--
作者：
Ingman, Wendy V.;Robertson, Sarah A.
TGF beta 1 is a multifunctional cytokine implicated in gonad and secondary sex organ development, steroidogenesis, and spermatogenesis. To determine the physiological requirement for TGF beta 1 in male reproduction, Tgfb1 null mutant mice on a Prkdc(scid) immunodeficient background were studied. TGF beta 1deficient males did not deposit sperm or induce pseudopregnancy in females, despite an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes. Serum and intratesticular testosterone and serum androstenedione were severely diminished in TGF beta 1-deficient males. Testosterone deficiency was secondary to disrupted pituitary gonadotropin secretion because serum LH and to a lesser extent serum FSH were reduced, and exogenous LH replacement with human chorionic gonadotropin (hCG) induced serum testosterone to control levels. In the majority of TGF beta 1-deficient males, spermatogenesis was normal and sperm were developmentally competent as assessed by in vitro fertilization. Analysis of sexual behavior revealed that although TGF beta 1 null males showed avid interest in females and engaged in mounting activity, intromission was infrequent and brief, and ejaculation was not attained. Administration of testosterone to adult males, even after neonatal androgenization, was ineffective in restoring sexual function; however, erectile reflexes and ejaculation could be induced by electrical stimulation. These studies demonstrate the profound effect of genetic deficiency in TGF beta 1 on male fertility, implicating this cytokine in essential roles in the hypothalamicpituitary-gonadal axis and in testosterone-independent regulation of mating competence.
