Impaired fertility in female mice lacking urinary trypsin inhibitor

Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is fo und in blood and urine. To investigate the physiological functions of UTI i n vivo we generated UTI deficient mice by gene targeting. The mice showed n o obvious abnormalities and appeared healthy. However, the females displaye d a severe reduction in fertility. Wild-type embryos developed normally whe n transplanted into UTI-deficient female mice, suggesting that UTI-deficien t females have a normal ability to maintain pregnancy. The number of natura lly ovulated oocytes from UTI deficient mice was greatly reduced compared w ith that from wildtype mice. Histologically, oocytes with disorganized coro na radiata were frequently seen in the ovaries of UTI-deficient mice after hormonal stimulation. When ovaries from UTI deficient mice were transplante d into wild-type mice, pups derived from the transplanted ovaries were obta ined, suggesting that the ovary of UTI-deficient mice functions normally if UTI is supplied from the systemic circulation. These re suits demonstrate that UTI plays an important role in the formation of the stable cumulus ooc yte complex that is essential for oocyte maturation and ovulation, (C) 2001 Academic Press.