In most mammals including human, testis differentiation is initiated by expression of a gene on the Y-chromosome (Sry). However, how the protein encoded by Sry interacts with other genes in the downstream cascade is not clearly understood. SRY is required for differentiation of Sertoli cells and later Sertoli cells induce differentiation of other cell types in the fetal testis. In adult testis, Sertoli cells support germ cells and nurture them. At adulthood, any effects on sperm producing germ cells are thought to be mediated by Sertoli cells. I am trying to unravel molecular mechanisms underlying SRY-mediated testis differentiation in male fetuses. It is hypothesized that any abnormality in critical processes of fetal germ and somatic (Sertoli and Leydig) cell development may lead to infertility or serious reproductive diseases in male humans.
Most of the diseases that occur at adulthood have been believed to have a fetal origin. Gestating mothers are constantly exposed to environmental stress directly or indirectly. The major developmental events are in process in fetus during gestation. In many cases, maternal exposure causes an imbalance in molecular developmental processes, leading to serious developmental defects in newborns and serious diseases at adulthood. Any abnormality in fetal gonadal development caused by environmental stress may lead to serious reproductive diseases later in life. With ample information on how these reproductive organs develop, I would like to dissect molecular mechanisms (genetic and epigenetic) associated with fetal origins of adult diseases in a wide variety of experimental models so that findings can be translated to human disease cases. Genetic and epigenetic biomarkers will be discovered for detecting diseases early on and, hence, appropriate preventive measures can be taken.
