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Skinner Laboratory Research Summary

Research Summary

General interest is in mammalian reproduction and environmental epigenetics on a systems biology level. The laboratory has had a long standing research program to study gonadal development and function on a molecular, cellular and physiological level (systems biology). More recently, the ability of environmental factors to act on gonadal development has been shown to cause the epigenetic transgenerational inheritance of disease and phenotypic variation which impacts areas of biology such as medicine or evolution. This has now become a predominant research program in the lab.

Basic reproductive biology research projects involve 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. 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. 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 testis and ovary development and function on a systems biology level.

Previously we have found that environmental toxicants (e.g. endocrine disruptors) have the ability to modify local cell-cell interactions in the testis and ovary during fetal development that influences epigenetic programming of the germline. If gestating females are exposed to environmental toxicants at the time of fetal gonadal sex determination, a number of adult onset diseases develop. Interestingly this phenotype is transgenerational, such that what your pregnant great grandmother was exposed to may cause disease in you with no subsequent exposure. This has been termed epigenetic transgenerational inheritance. An epigenetic effect on the programming of the germ-line was observed and is the causal factor in this epigenetic transgenerational effect of environmental toxicants. In addition to effects on reproduction, numerous other adult onset disease sates are observed including cancer, prostate disease, kidney disease, obesity, immune abnormalities and behavior effects. Further characterization of this phenomena and its impact on disease etiology and evolutionary biology is in progress.

Epigenetics Definition and Background
Epigenetic Transgenerational Inheritance