My laboratory has had a long standing research program to study gonadal development and function on a molecular and cellular level. More recently, the ability of environmental factors to act on gonadal development has been shown to cause epigenetic transgenerational disease. This has now become a predominant research program in the lab. Research is focused on the investigation of how different cell types in a tissue interact and communicate to regulate cellular growth and differentiation, with emphasis in the area of reproductive biology. The cells of interest and specific interactions investigated have an integral role in controlling the development of the spermatozoa and oocyte. Our observations indicate that the mesenchymal cells of both the testis and ovary produce inducer substances that alter the differentiation and function of adjacent epithelial cells. The role that reproductive hormones (e.g. steroids) and growth factors (e.g. transforming growth factors, neurotropins) have in regulating these mesenchymal-epithelial cell interactions is under investigation. The characterization and molecular cloning of novel mesenchymally-derived inducer substances is in progress, as well as an investigation of the molecular and cellular pharmacology of these factors. How these factors promote the transcriptional regulation of cellular differentiation is being investigated through an analysis of the role of a unique class of transcription factors, basic-helix-loop-helix (bHLH) factors. Abnormal expression of these mesenchymal factors is postulated to be associated with the carcinogenesis of these tissues (e.g. ovarian cancer). A hypothesis being examined is that a family of mesenchymal inducer factors exist that are essential for epithelial cell differentiation during development and maintenance of cellular differentiation in the adult.
Recently we have found that environmental toxicants (i.e. endocrine disruptors) have the ability to modify local cell-cell interactions in the testis and ovary. If gestating mothers are exposed to endocrine disruptors at the time of gonadal sex determination, a sub-fertility phenotype is observed in the adult male. Interestingly this phenotype is transgenerational. An epigenetic effect on the programming of the male germ-line was observed and is the causal factor in this epigenetic transgenerational effect of endocrine disruptors. In addition to effects on reproduction numerous other disease sates are observed. Further characterization of this phenomena and its impact on disease etiology and reproduction is in progress.