Grant: Project Grant

We are studying the role of a transcription factor (a protein that participates in turning genes on or off), called GATA4. GATA4 was first discovered for its essential role in regulating the development of the heart. GATA factors are also prominently expressed in reproductive organs (testis and ovary). GATA4 is required for early gonad development in both sexes; without this factor differences of sex development such as ambiguous genitalia can occur. GATA4 also appears to be important for the function of the mature gonad since the absence of GATA4 can cause male and female infertility. GATA4 gene mutations are known to affect human health and some GATA4 mutations have been associated with disrupted testicular development in men. The objective of our research is to define the mechanism of action of GATA4 (i.e., how it accomplishes its functions) in a cell type within the testis, called Leydig cells, that produces testosterone. Abnormal Leydig cell development and function results in insufficient hormone production leading to impaired male reproductive health. Despite the physiological importance of Leydig cells, how their development and function is controlled remains poorly understood. Using unique mouse models we have recently generated, our research proposes to investigate how GATA4 controls the differentiation and function of Leydig cells at different times during life (fetal development, around birth, at puberty, and adulthood). Understanding the role of GATA4 in Leydig cells 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 the better diagnosis and treatment of several human pathologies associated with defective Leydig cells and/or inadequate testosterone production.