Abstract
Establishment and maintenance of pregnancy in the pig involves intricate communication between the developing conceptuses and the maternal endometrium. This process occurs during trophoblast elongation which is spaciotemporally associated with conceptus synthesis and release of IL1B concomitant with pregnancy-specific endometrial up-regulation of IL-1 receptors, providing the potential for activation of the transcription factor, NFKB. The objective of the current investigation was to determine changes in expression and cellular localization of NFKB and associated factors during the estrous cycle and early pregnancy in the pig. In situ hybridization was used to localize changes in PGR, ESR1, and TNFRSF11A during the peri-implantation period. Quantitative RT-PCR was utilized to demonstrate gene expression changes for NFKB1, RELA, TNFRSF11A, TLR4, NFKBIA and NFKBIB. Transcription factor ELISA demonstrated an overall increase in RELA during the peri-implantation period in both cyclic and pregnant gilts. While the presence of TNFSF11A and TLR4 were both detected, TLR4 expression changes were temporally associated with NFKB expression and activation. Collectively, these data demonstrate that NFKB activation may occur during the period of uterine receptivity in both the cyclic and pregnant endometrium.
Highlights
Establishment of pregnancy requires changes in the uterus that allow for attachment and implantation of a developing conceptus
No difference in the amount of RELA in the nuclear fraction of the endometria was observed between the days of the estrous cycle and pregnancy (Figure 1)
We have suggested a relationship between progesterone receptor (PGR) expression and the activation of NFKB in the endometrial luminal epithelium (LE) regulates the transcription of specific genes such as prostaglandin synthase-2 (PTGS2) [4,9]
Summary
Establishment of pregnancy requires changes in the uterus that allow for attachment and implantation of a developing conceptus. Given the fact that the uterine transcriptional profile during early conceptus development resembles a proinflammatory response, it is possible that the transcription factor, nuclear factor κB (NFKB), is involved in the establishment of pregnancy. Plasma concentrations of progesterone are high during diestrus and cause a specific down-regulation of progesterone receptor (PGR) protein in the luminal epithelium of pigs on days 10 to 12 of the estrous cycle and pregnancy [8]. The down-regulation of PGR in the luminal epithelium during the peri-implantation period is associated with changes in endometrial gene expression that lead to either uterine receptivity for conceptus development and attachment or to pathways that release prostaglandin F2α to regress the corpora lutea and initiate a return to estrus [9]. The association between PGR down-regulation and the opening of the implantation window is not limited to the pig as PGR down-regulation in the uterine luminal epithelium occurs prior to implantation in humans [10,11], baboons [12], sheep [13], cattle [14] and horses [15]
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