Timing of exogenous progesterone administration is critical for embryo development and uterine gene expression in an ovine model of maternal constraint.

Progesterone (P4) administration in early pregnancy enhances embryo growth in sheep but is associated with decreased embryo survival. This study examined the effects of exogenous P4 administered during specific time periods between pregnancy Day 0 and Day 6 to determine the critical time point for advancement of embryo growth without pregnancy loss and to examine Day 6 and Day 19 endometrial gene expression. Suffolk (S) embryos were transferred into Cheviot (C) ewes that received exogenous P4 (CP4) on Days 0-3 (CP40-3), Days 0-6 (CP40-6), Days 2-4 (CP42-4) or Days 3-6 (CP43-6). Additionally, S embryos were transferred to C and S ewes that did not receive P4 (CnP4 and SnP4). Day 19 embryos from CP4 ewes were longer (P<0.05) than those from CnP4 ewes. CP42-4 ewes had embryos of similar size to those of CP40-3 and CP40-6 ewes but had higher pregnancy rates. There was altered expression of genes associated with embryo implantation and histotroph production: diacylglycerol-O-acyltransferase (DGAT2), hepatocyte growth factor (HGF) and prostaglandin endoperoxide synthase 2 (PTSG2) on Day 6 and endometrial galectin 15 (LGALS15) and mucin glycoprotein 1 (MUC1) on Day 19. This suggests that specific timing of P4 administration is critical to the enhanced embryo growth and survival observed. These findings provide a platform for further investigation aimed at advancing embryo development and survival.