Progesterone Regulates Endometrial Expression of SLC6A9 to Potentially Increase Glycine Transport to the Developing Pig Conceptus†.

Abstract

Histotroph is regulated by progesterone (P4) and other paracrine factors and contains amino acids essential for porcine conceptus (embryo/fetus and placental membranes) development. We hypothesized that P4 contributes to amino acid transport during pregnancy in pigs. Ovariectomized gilts received daily P4 or corn oil (CO) injections from Days 12 through 39 post-estrus. High-performance liquid chromatography (HPLC) determined increased abundances of several amino acids, including glycine, in uterine flushings from P4-treated gilts. Solute carrier transporters (SLCs) transport amino acids across membranes. Quantitative real-time PCR (qPCR) analyses revealed endometrial expression of SLC6A9 mRNA increased during the peri-implantation period of pregnancy. SLC7A8 and SLC38A1 mRNA expression also increased during that period but decreased later in pregnancy. SLC1A4, SLC1A5 and SLC7A10 mRNA expression was greatest later in pregnancy. Immunofluorescence analyses localized SLC6A9, which transports glycine exclusively, to the endometrial luminal epithelium from Day 12 through 25, uterine glandular epithelium throughout gestation, conceptus trophectoderm and endoderm between Days 15 and 20, and chorionic epithelia of inter-areolar and areolar chorionic epithelia (CE) between Days 40 and 60. Expression in inter-areolar regions decreased by Day 60 but remained high in the areolae. Expression of SLC6A9 was greater for endometrium from P4-treated than CO-treated pigs. These results illustrate the complexity of, and stage-dependent changes in, expression of amino acid transporters in endometria from pregnant pigs. The results suggest that transport of glycine into the uterine lumen and across the chorioallantois by SLC6A9 may be critical for delivery of this amino acid that is essential for conceptus development.