Grant: Project Grant

We are studying the role of a family of transcription factors (proteins that participate in turning genes on or off), called MEF2. MEF2 factors were first discovered for their essential role in regulating the development of the heart. MEF2 factors are also prominently expressed in the testis but not in the ovary. In the testis, MEF2 factors are found in Sertoli and Leydig cells throughout fetal and post-natal life. Our previous work using Sertoli and Leydig cell lines in culture revealed that MEF2 factors regulate the expression of several genes important for the function of these cells. In addition, MEF2 gene mutations are known to affect human health and some MEF2 mutations have been associated with disrupted testicular development and function in men. The objective of our research is to define the mechanism of action of MEF2 factors (i.e., how they accomplish their functions) in Sertoli and Leydig cell development and function using different mouse models where the Mef2 genes are rendered non-functional exclusively in Leydig cells, and exclusively in Sertoli cells. Understanding the role of MEF2 factors in testis formation and function is essential not only for establishing male/female sex differences during pregnancy and at puberty but also the maintenance of fertility in adulthood. Our research will hopefully lead to better diagnosis of several human pathologies associated with defective Sertoli and/or Leydig cells.