Abstract
In the mouse, opening of the vaginal cavity to the skin is a postnatal tissue remodeling, occurring around the fifth week of life. The tissue remodeling required to complete maturation of the female genital tract at the time of puberty depends on a hormonally triggered apoptosis-dependent process occurring in the lower part of the vaginal mucosa. However, the detailed mechanism of apoptosis induced by sex hormone is unknown. Our analysis disclosed that mice lacking the class IV semaphorin, Sema4D develop vaginal atresia resulting from the failure in vaginal opening. In order to analyze the mechanism of which Sema4D-deficient mice develop vaginal atresia, TUNEL assay was performed on vaginal mucosa from 5-week-old mice. As a result, apoptotic cells in vaginal mucosa were significantly less in Sema4D-deficient mice compared to wild-type mice. To demonstrate the apoptosis-inducing activity of Sema4D, we performed a rescue experiment by placing back recombinant Sema4D to cultured vaginal epithelial cells from Sema4D-deficient mice. Sema4D induced a significant apoptosis of vaginal epithelial cells. Thus Sema4D may play a non-redundant role in the tissue remodeling by inducing apoptosis in vaginal epithelial cells of 5-week-old mice. [J Physiol Sci. 2007;57 Suppl:S178]
