title: Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.
abstract: Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new "Organ-on-Chip" models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease.
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: kaylon.bruner-tran@vanderbilt.edu.
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 37232, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Gnecco
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
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 37232, USA.
authors.forename: Dana R
authors.initials: DR
authors.lastname: Glore
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pensabene
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; VA Tennessee Valley Healthcare System, Nashville TN 37212, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Osteen
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004715:Endometriosis / Q000139:chemically induced / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D052244:Endocrine Disruptors; D000072317:Polychlorinated Dibenzodioxins
keywords: Adenomyosis; Endometriosis; Epigenetics; Preterm birth; TCDD; Transgenerational