SAT-141 - The Effects of Progesterone on Lipid Metabolism in the Uterine Epithelium

Approximately 50% of pregnancies fail, mostly prior to or during implantation. Prior to implantation, embryos are dependent on uterine secretions, called histotroph. Histotroph consists of a complex mixture of nutrients that support the growth of the embryo during early pregnancy, secreted due to the actions of progesterone. We previously found that progesterone increased NADPH production in bovine uterine epithelial (BUTE) cells, leading us to hypothesize that progesterone stimulates lipid metabolism in the uterine epithelium. Reanalysis of our previous dataset (GSE269076) showed that progesterone increased the expression of 23 out of 25 genes from a curated list of genes related to lipogenesis and lipid trafficking. Untargeted lipidomics of control and progesterone-treated (10 µM) BUTE cells and conditioned media detected 1,607 lipid species across 14 distinct lipid subclasses. The two major sub-classes of lipid species detected were triglycerides (37%) and phosphatidylcholines (31%). Partial Least Squares-Discriminant Analysis (PLS-DA) showed separation using lipid features between control and progesterone-treated BUTE cells. In cells, progesterone tended to (P=0.066) increase the relative abundance of triacylglycerols (TAGs) and did increase the levels of phosphatidylcholines (P < 0.05). In conditioned media, the most significantly abundant lipid subclasses were triacylglycerols (TAGs) (30.5%), ceramides (11.1%), and ether triacylglycerols (O-TAGs) (11.1%), with most lipid species having a chain length >32 and with low unsaturation levels. More specifically, progesterone significantly decreased the levels of 3 and increased the levels of 130 lipid species, increasing the concentrations of phosphatidylcholines, oxidized triglycerides, and ether triglycerides. In agreement, progesterone also increased lipid droplet storage in BUTE cells. To evaluate the potential role of progesterone in vivo, we performed immunohistochemistry on endometrial biopsies collected from the cow uterus on days 1 (low progesterone) and 11 (high progesterone). We found that lipid storage and esterification enzymes LPIN1 and DGAT2 were more highly expressed in the glandular epithelium on day 11. These results suggest that progesterone increases lipid synthesis and secretion by the uterine epithelium, likely to support preimplantation embryo development.

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