MP75-14 E2F1 IS A MASTER REGULATOR OF TESTICULAR DESCENT AND SPERMATOGENESIS VIA ITS REGULATION OF THE WNT4 PATHWAY

INTRODUCTION AND OBJECTIVES:Infertility affects 15% of couples trying to conceive. The etiology for most cases of male infertility is unknown. However, a well-recognized contributing cause of male infertility is cryptorchidism, the most common birth defect in men. Gene-dosage changes resulting from microdeletions and microduplications encompassing E2F1 are present in a subset of infertile men, including some that were cryptorchid. It was hypothesized that gene-dosage changes in E2f1 can cause cryptorchidism.METHODS:Detailed phenotypic analyses of E2f1 null mice were conducted to assess testicular development, location and function.RESULTS:E2f1-null mice had inguinal cryptorchidism with severe structural defects of the gubernaculum and progressive loss of testicular germ cells that culminated in infertility. Testicular failure was associated with significantly decreased testicular weight and impaired sperm production. Inactivation of E2f1 resulted in the loss of germ cell polarity and abnormal tight juncti...