Activation of the transcription factor, nuclear factor kappa-B, during the estrous cycle and early pregnancy in the pig

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.

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

“…Estrogen receptor (ESR) expression in LE and glandular epithelium (GE) of the endometrium (Geisert et al 1993) and in the conceptus (Kowalski et al 2002) coincides with estrogen secretion from the conceptus, suggesting both autocrine and paracrine actions. On day 12 of pregnancy, ESR1 mRNA abundance is elevated in the LE (Ross et al 2010). Both a sufficient amount of conceptus estrogen synthesis and timing of the endometrial exposure to estrogen is crucial for establishment of pregnancy.…”

“…Therefore, the effects of ovarian progesterone on expression of many factors in LE may be mediated indirectly either by progesterone-induced progestamedins produced by PGR-positive stromal cells or by induction of molecules in LE that causes downregulation of PGR to regulate expression of endometrial genes , Ka et al 2007). Downregulation of PGR in LE and GE coincides with activation of nuclear factor kappa B (NFKB); however, a role of this transcription factor in inhibition of PGR expression was not confirmed in the pig (Ross et al 2010, Mathew et al 2011. NFKB activation is an important component in opening the implantation window in pigs and is probably involved in the increase in endometrial PTGS2 expression on day 12 after estrus .…”

Interleukins, interferons, and establishment of pregnancy in pigs

“…An increase in endometrial blood vessel permeability is temporally associated with conceptus release of IL1β2 (Keys & King 1988). The IL1β1 and IL1β2 feedback loop may be partially controlled by NF-κB transcription factors activated by IL1 (Ross et al 2010, Mathew et al 2015. It is well known that IL1β and NFKβ subunits are regulated by NF-κB activity.…”

“…These cytokines are expressed during the synthesis of conceptus estrogens for maternal recognition of pregnancy (Bazer & Thatcher 1977). Other proinflammatory cytokines are present at the conceptus-maternal interface during establishment of pregnancy in pigs including interleukin-6 (IL6), interleukin-18 (IL18), leukemia inhibitory factor (LIF), and tumor necrosis factor alpha (TNFα) (Yu et al 1998, Modric´ et al 2000, Ashworth et al 2010, Blitek et al 2012. Many of these cytokines stimulate production and release of prostaglandins (PG) that may contribute to the inflammatory environment within the endometrium (Waclawik 2011.…”

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

“…TLR-mediated cell signaling cascades involve the cytokine inductor nuclear factor kappa b (NFKB) and interferon regulatory factors (IRFs) to induce type I interferons (IFNs) (Kumar et al 2009). Both of these pathways are actively regulated in the female reproductive tract, and their deregulation leads to infertility and disease (Spencer et al 1998, King et al 2001, Fleming et al 2009, Ross et al 2010, Hadfield et al 2011, Maybin et al 2011.…”