Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Since humans and animals are most sensitive to toxicant exposure during development, we previously developed a mouse model of in utero TCDD exposure in order to examine the impact of this toxicant on adult reproductive function. Our initial in utero toxicant-exposure study revealed a dose-dependent reduction in uterine sensitivity to progesterone; however, we did not previously explore establishment or maintenance of pregnancy. Thus, in the current study, we examined pregnancy outcomes in adult C57BL/6 mice with a history of developmental TCDD exposure. Herein we demonstrate reduced fertility and an increased incidence of premature birth (PTB) in F1 mice exposed in utero to TCDD as well as in three subsequent generations. Finally, our studies revealed that mice with a history of developmental TCDD exposure exhibit an increased sensitivity to inflammation which further negatively impacted gestation length in all generations examined.
Bruner-Tran
Kaylon L
KL
Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. kaylon.bruner-tran@vanderbilt.edu
Osteen
Kevin G
KG
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000235:genetics; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins