Rodent Models for Translational Research in Endometriosis.

Endometriosis is a prevalent gynecological condition where fragments of the endometrial lining attach and grow in ectopic locations, primarily the peritoneal cavity. These endometriotic lesions are associated with infertility and pain in women during their reproductive years. Ethical restrictions on experimentation in women have driven the evolution of animal models to study human diseases, including endometriosis. Such models facilitate studies of principles and regulators underlying mechanisms of disease without confounding influences. They enable studies which integrate cellular & molecular mechanisms, as well as examine dietary, environmental & other effects. The objective of this presentation is to provide an overview of different models which have provided insights into how the microenvironment of the peritoneal cavity, the environment in which we live and the impact of surgery alter the pathogenesis and pathophysiologies of endometriosis. Results from three different models for endometriosis in rodents will demonstrate: 1) molecular mechanisms of endometriosis-associated infertility and how modulation of TIMP1 in the peritoneal microenvironment may be developed as a novel mechanism to restore reproductive function in an endometriosis model in the rat; 2) differential gene expression with gene ontology enrichment analysis associated with extracellular matrix remodeling, cell adhesions, immune function, cell growth, and angiogenesis during the estrous cycle and pregnancy in both the eutopic and ectopic endometriotic lesions and as well as the overlapping and distinct effects bisphenol A and diethylstilbestrol on of fetal programming of the endometrium in an endometriosis model in the mouse and 3) the impact of recent surgery on development of endometriosis-related adhesions in a chimeric mouse model and the therapeutic efficacy of pioglitazone targeting inflammation and angiogenesis. In conclusion, gene or proteomic targeting, control of epigenetic modifications and surgical manipulations in endometriosis models in rodents may be used to help develop novel translational diagnostic and therapeutic approaches for human medicine. Portions of this work were supported by the NIH NICHD HD057445 (KST), HD056441-01 (SCN), NICHD R01HD055648 (KGO), RO3 HD052012 (KBT), K23HD043952 (DIL) and the Endometriosis Association (KGO).