Paternal TCDD Exposure Alters the Placental Epigenome

Preterm birth (PTB), spontaneous parturition prior to 37 weeks gestation, is the leading cause of neonatal mortality. We previously demonstrated that developmental exposure of male mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with reduced sperm quantity/quality in adulthood and their control mating partners frequently delivered preterm. Reproductive defects persisted in the F2 and F3 descendants and mating partners also exhibited an enhanced risk of spontaneous PTB. Reproductive changes in the F3 males, the first generation without direct TCDD exposure, suggest epigenetic alterations occurred in the male germline. Importantly, the sperm epigenome impacts development of the placenta, a tissue which is known to influence the timing of parturition. Therefore, we conducted an epigenetic microarray analysis of control and F1 male derived placentae obtained on E18.5 of pregnancy. DNA from 3 control placentae was compared to 5 placentae from females mated to F1 males. Each placenta was from a different pregnancy. Decidua was removed.