Endometriosis is a chronic inflammatory disorder defined as the presence of endometrial glands and stroma outside the endometrial cavity. The causes of endometriosis onset are still unknown, but a relationship between stress and abnormal functioning of the hypothalamic-pituitary-adrenal axis (HPA) has been documented. In these chronic conditions, prolonged periods of initial HPA axis activation might be followed by a state of hypocortisolism, which might result as an adaptive response to sustained HPA activity. The well-characterized model of animal environmental enrichment has been proven to stabilize HPA axis activity. Environmental enrichment shares several components of behavioral therapies in humans making it a suitable model to study its use as complementary therapy for chronic conditions such as endometriosis. In light of these previous findings, we hypothesize that environmental enrichment, as a model of behavioral therapy, will reduce the symptoms of endometriosis. This hypothesis will be tested in two specific aims:
The first aim will use environmental enrichment in the rat model of endometriosis to test whether the severity of the disease is diminished as measured by behavioral and molecular parameters of HPA axis activity.
Aim 2 consists of two experiments where the first one will characterize the HPA axis activity during the progression (7 and 60 days) of endometriosis. The second experiment will use a CRFR1 antagonist to attempt to regulate HPA axis activity during the initial phases of the disease establishment in comparison to environmental enrichment outcomes. In parallel to the proposed research plan, a series of activities have been designed to enhance the candidate's career development, teaching and curriculum building skills. The candidate will participate in a series of seminars, focused courses and training that will enhance her knowledge and applicability of complementary and alternative medicine (CAM) practices in research. This will ultimately lead to the integration of a CAM-oriented elective course to be offered to graduate students from Ponce School of Medicine during which the candidate can showcase her research findings. The expected outcomes of the proposed career award are the following 1) Provide empirical data leading towards the increased use of behavioral therapy for endometriosis treatment, 2) Improve curriculum building skills that will lead towards the implementation of CAM course and offerings at Ponce School of Medicine, and 3) Train the candidate to achieve her independence as an academic researcher leading towards obtaining independent funding.

Public Health Relevance

The proposed research is relevant to public health because endometriosis takes a physical and psychological toll on women by significantly decreasing their quality of life and work productivity by an average of 18 days during a one-year period. Current therapies are highly invasive or significantly disrupt the endocrine and reproductive systems, thus complementary and/or alternative therapies for endometriosis are highly needed. Understanding how to alleviate stress produced by endometriosis progression using behavioral therapy will help alleviate the symptoms burden suffered by women, especially on those women where endometriosis is suspected or misdiagnosed but not confirmed. In addition, the training that Dr. Torres-Reveron will receive can ultimately lead to increase educational and research capabilities that will result in the application of complementary and alternative medicine practices in both research and medical settings.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Academic/Teacher Award (ATA) (K07)
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Special Emphasis Panel (ZAT1)
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Duffy, Linda C
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University of Texas Rio Grande Valley
Schools of Medicine
United States
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Colón-Caraballo, Mariano; Torres-Reverón, Annelyn; Soto-Vargas, John Lee et al. (2018) Effects of histone methyltransferase inhibition in endometriosis. Biol Reprod 99:293-307
Torres-Reverón, Annelyn; Rivera, Leslie L; Flores, Idhaliz et al. (2018) Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression. Reprod Sci 25:1336-1348
Ramos-Ortolaza, Dinah L; Doreste-Mendez, Raura J; Alvarado-Torres, John K et al. (2017) Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress. Behav Brain Res 328:115-122
Torres-Reverón, Annelyn; Palermo, Karylane; Hernández-López, Anixa et al. (2016) Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray. Reprod Sci 23:1158-67