Participating Faculty

Molecular And Cellular Control Of Testis And Ovary Biology And
Development, As Well As Epigenetic Transgenerational Actions Of
Environmental Compounds On Reproduction And Disease

Research is focused on the molecular and cellular aspects of reproduction, with emphasis in the area of testis and ovary cell 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. How these factors promote the transcriptional regulation of cellular differentiation required for gonadal development is being investigated through an analysis of the role of a unique class of transcription factors, basic-helix-loop-helix (bHLH) factors. Information obtained from these studies is necessary before novel therapeutic agents can be designed and targeted at reproductive cells for the prevention of infertility or to act as contraceptives. The research is designed to understand the cell biology of the testis and ovary on a molecular level, as well as provide insight into the mechanisms regulating the cellular functions and cell-cell interactions in other organs. 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.

An investigation of the effects of environmental toxicants on gonadal development has been initiated.  Recently the impact of endocrine disruptors on embryonic testis and ovary development demonstrated an epigenetic transgenerational phenotype on adult male fertility.  Exposure of the embryonic testis at the time of sex determination caused an epigenetic imprinted reprogramming of the male germ-line that causes a variety of disease states in the adult and this phenotype is transferred through the male germ-line to all subsequent generations.  The underlying mechanism and phenotype of this epigenetic transgenerational phenomenon is being investigated.

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