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

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Abstract
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 mRNA was not different between pigs injected with P4 compared with pigs injected with CO, and SPP1 was not present in the GE of P4-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. Abstract 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 mRNA was not different between pigs injected with P4 compared with pigs injected with CO, and SPP1 was not present in the GE of P4-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.

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