Hormonal Regulation of Urokinase- and Tissue-Type Plasminogen Activator in Mouse Sertoli Cells

A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs. However, the proteolytic activity results from a balance between enzyme activity and inhibitors. Hormonal stimulation decreased the expression of the inhibitor PAI-1, suggesting that the increase in proteolytic activity might depend on the decreased production of PAI-1. The expression of the two enzymes and their inhibitor depends on the seminiferous epithelium stage. We observed higher uPA mRNA levels at stages VII-VIII and IX-XII, tPA peaks at stages VII-VIII, and PAI-1 mRNA levels decreased at stages VII-VIII and IX-XII. The testes from mice lacking the uPA gene (uPA^-/-) presented statistically smaller sizes and weights. Histological analysis of uPA^-/-animals showed tubular morphology defects and atypical residual bodies (RB), suggesting a defect in Sertoli cell phagocytosis. Moreover, we show lower sperm concentration and motility in uPA^-/- mice. These data suggested an effective deficiency of testicular development in the absence of uPA.