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RESEARCH SUMMARY: 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 cell 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. 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.
REPRESENTATIVE PUBLICATIONS: Anway M, Cupp AS, Uzumcu M, Skinner MK. (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466-1469
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