De novo synthesis of sphingolipids is essential for decidualization in mice

Abstract

Sphingolipids play multiple roles in membrane structure, signal transduction, stress responses, neural development and immune reaction. The rate of de novo synthesis pathway of sphingolipids is regulated by two key enzymes, serine palmitoyltransferase (SPT), and ketoreductase (Kds). Here, we find that the mRNA levels of three subunits of the SPT holoenzyme (Sptlc1, Sptlc2, and Ssspta) are significantly up-regulated in mouse uterine stromal cells during decidualization. The expression of Kds, which reduces 3-keto-dihydrosphingosine to dihydrosphingosine, is co-localized with Sptlc1 in mouse uteri during early pregnancy. Moreover, L-Cycloserine, a specific inhibitor of SPT, can significantly decrease the weight and number of implantation sites, and impede the decidualization process in mouse uterine stromal cells, suggesting that blockage of de novo sphingolipid synthesis may cause defective decidualization and early pregnancy loss in mice. In addition, this study also shows progesterone (P4) can stimulate the expression of both Sptlc2 and Ssspta in mouse uterus. Therefore, our study shows that de novo synthesis of sphingolipids is necessary in implantation and plays a key role in decidualization of mouse.