Science Inventory

Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction

Citation:

Miller, C., K. Lavrich, D. Freeborn, P. Kodavanti, U. Kodavanti, AND J. Dye. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction. Experimental Biology, Chicago, IL, April 22 - 26, 2017.

Impact/Purpose:

Little is known about the mechanisms that drive placental maladaptation that can contribute to compromised fetal development, thus we sought to explore them in our model of IUGR.

Description:

Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularly in terms of increased placental weight and mitochondrial DNA levels, have been demonstrated in intrauterine growth restricted (IUGR) fetuses. Little is known about the mechanisms that drive placental maladaptation that can contribute to compromised fetal development, thus we sought to explore them in our model of IUGR. In the current study we developed a model of IUGR by exposing Long Evans dams to filtered air or 0.8 ppm ozone, 4hr/day during the implantation period. At gestational day 21, pups from ozone exposed dams had reduced weight compared to air control pups, demonstrating the development of IUGR. Furthermore, placenta to pup weight was elevated in both male and female IUGR pups, suggesting impaired placental development. Bioenergetics, measured as oxygen consumption rate (OCR), on fresh placental mitochondria were measured using the Seahorse XF96 analyzer. While IUGR did not impact female placental OCR at any point in the assay, placentas of IUGR males had increased total OCR relative to controls. Total ATP production remained unchanged between control and IUGR male placentas, however a significant proton leak was found in the mitochondria from male IUGR placentas compared to controls. Despite apparent sex differences in placental mitochondrial OCR, both sexes of IUGR pups had elevated mitochondrial biogenesis and mitochondrial DNA levels compared to their respective controls. Additional gene expression experiments demonstrated that female IUGR pups have reduced Sod1 and increased Bcl2 expression compared to control female placentas, suggestive of increased apoptosis. Interestingly, this difference was not observed in males. Together our data supports the hypothesis that placental mitochondrial dysfunction is related to reduced fetal weight. However, we demonstrate clear sex differences of IUGR on mitochondrial function and activity in the placenta. Our findings support the emerging importance of mitochondrial health in the etiology of environmental stress-induced IUGR, as well as the importance of utilizing a sex-specific approach to investigate prenatal outcomes. This abstract does not reflect US EPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/POSTER)
Product Published Date: 04/24/2017
Record Last Revised: 10/17/2017
OMB Category: Other
Record ID: 337902

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH