Effects of long-term progesterone exposure on porcine uterine gene expression: Progesterone alone does not induce secreted phosphoprotein 1 (osteopontin) in glandular epithelium

Pigs experience significant conceptus loss near mid-gestation, correlating with increasing glandular epithelial (GE) development and secretory activity. Secreted phosphoprotein 1 (SPP1, osteopontin) increases in GE between days 30 and 40 of pregnancy and is expressed in the GE of day 90 pseudopregnant pigs, suggesting that progesterone (P₄) from corpora lutea is responsible for induction of SPP1 in GE. In this study, pigs were ovariectomized and treated daily with P₄ to assess effects of 40 days of P₄ exposure on SPP1, P₄ receptor (PGR), uteroferrin (ACP5), and fibroblast growth factor 7 (FGF7) expression in porcine endometria. PGR mRNA decreased in pigs injected with P₄ compared with pigs injected with corn oil (CO), and PGRs were downregulated in the luminal epithelium (LE) and GE. ACP5 mRNA increased in pigs injected with P₄ compared with pigs injected with CO, and ACP5 was induced in the GE of P₄-treated pigs. FGF7 mRNA increased in pigs injected with P₄ compared with pigs injected with CO, and FGF7 was induced in the LE and GE of P₄-treated pigs. SPP1 mRNAwas not different between pigs injected with P₄ compared with pigs injected with CO, and SPP1 was not present in the GE of P ₄-treated pigs. Therefore, long-term P₄, in the absence of ovarian and/or conceptus factors, does not induce SPP1 expression in GE. We hypothesize that a servomechanism involving sequential effects of multiple hormones and cytokines, similar to those for sheep and humans, is required for GE differentiation and function, including the synthesis and secretion of SPP1.