Uteroplacental secretion of progesterone and estradiol-17ß in an ovine model of intrauterine growth restriction

Authors: LEMLEY, CALEB - Mississippi State University; CAMACHO, LETICIA - North Dakota State University; HALLFORD, DENNIS - New Mexico State University; VONNAHME, KIMBERLY - North Dakota State University

Submitted to: Animal Reproduction Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/3/2018
Publication Date: 4/4/2018
Citation: Lemley, C., Camacho, L., Hallford, D., Vonnahme, K. 2018. Uteroplacental secretion of progesterone and estradiol-17ß in an ovine model of intrauterine growth restriction. Animal Reproduction Science. 193:68-78.

Interpretive Summary: Normal pregnancy in sheep relies heavily on placental secretion of progesterone during the last half of gestation. Several ovine models of fetal and placental growth restriction (e.g., maternal nutritional plane, maternal age, heat stress, hypoxic stress, and fetal number) have been developed to ascertain the relationship between endocrine status and placental nutrient delivery to the fetus. Maternal nutrient restriction impairs uterine and umbilical blood flow, which is associated with the magnitude of fetal growth restriction. In addition to the observed changes in uterine blood flow, maternal nutrition alters peripheral concentrations of hormones, which can have dramatic effects on metabolism and functional capacity of the placenta. The current study demonstrates an increase in placental steroid synthesizing capabilities in conjunction with a decrease in placental steroid inactivation following maternal nutrient restriction. In addition, the alterations in estrogen metabolizing enzymes in both the maternal portion of the placenta and maternal liver are important to fetal and placental development as metabolites from these pathways can modulate uterine blood flow. These enzymatic pathways could be targeted with pharmacologically active cytochrome P450 inhibitors or inducers during specific time points of gestation to alter hormone capacity of the placenta.

Technical Abstract: Using a mid to late gestation model of intrauterine growth restriction, uteroplacental secretion of progesterone and estradiol-17ß were examined. From day 50 to 130 of gestation, 31 ewe lambs were allocated to receive 100% (ADQ) or 60% (RES) of nutrient requirements. At day 130, umbilical and uterine artery blood flows were determined and blood samples were collected from maternal saphenous artery, gravid uterine vein, umbilical vein, and umbilical artery. Uteroplacental secretion of progesterone was increased in RES compared to ADQ fed dams. There was a net secretion and net metabolism of estradiol-17ß in RES, and ADQ fed dams, respectively. In relation to steroid synthesis, cotyledonary abundance of steroidogenic acute regulatory protein was greater in RES compared with ADQ fed dams, while abundance of aromatase was not different between dietary treatments. Caruncular aldo-keto reductase 1C abundance was less in RES compared to ADQ fed dams. The increase in progesterone secretion, therefore, is due in part to an increase in synthesis and a decrease in placental catabolism. Caruncular cytochrome P450 3A, which catalyzes the conversion of estrogens to catechol-estrogens, was in lesser abundance in RES compared to ADQ fed dams. Opposite responses in estradiol-17ß uteroplacental secretion compared with metabolism may be mediated through placental estrogen metabolism via cytochrome P450 enzymes.