title: The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans.
abstract: In a murine model, we have linked early life toxicant exposure to reduced uterine sensitivity to progesterone, a phenotype we had previously associated with inflammation in endometriosis patients. Subsequent studies revealed that developmental toxicant exposure not only reduces fertility in male and female mice but also negatively impacts pregnancy leading to spontaneous preterm birth (PTB). An epigenetic alteration of the progesterone receptor gene correlated with reduced fertility and adverse pregnancy outcomes and persisted in multiple generations of mice in the absence of an additional toxicant exposure. Gene-environment interactions in women may explain why some patients "at risk" for PTB deliver at term while others without known risks deliver early. Our model provides a unique system to unravel the interactive influences of inflammation and reduced progesterone responsiveness on PTB and suggests that therapy needs to begin prior to pregnancy (and involve both partners) rather than once the inflammatory cascade has been initiated.
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology Vanderbilt University School of Medicine, Nashville, TN, USA 37232.
authors.forename: Kaylon L
authors.initials: KL
authors.lastname: Bruner-Tran
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology Vanderbilt University School of Medicine, Nashville, TN, USA 37232.
authors.forename: David
authors.initials: D
authors.lastname: Resuehr
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology Vanderbilt University School of Medicine, Nashville, TN, USA 37232.
authors.forename: Tianbing
authors.initials: T
authors.lastname: Ding
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology Vanderbilt University School of Medicine, Nashville, TN, USA 37232.
authors.forename: John A
authors.initials: JA
authors.lastname: Lucas
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology Vanderbilt University School of Medicine, Nashville, TN, USA 37232.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Osteen