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

Abstract

Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F 2a (PGF 2a ) and E 2 (PGE 2 ) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE 2 . Conceptus PGE 2 could be amplified by PGE 2 feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon g and interferon d, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

“…Endometrial PTGS-derived PGF 2a and PGE 2 are crucial in the regulation of the CL activity through respective luteolytic or luteotrophic actions in various species [54,55]. PGs significance has been highlighted in the regulation of ovulation, the CL functions, maternal recognition of pregnancy, implantation and parturition [56].…”

Interleukins, interferons, and establishment of pregnancy in pigs

“…It is hypothesized that binding of estrogens to surface epithelial ESR1 stimulates the secretion of 'estromedins' such as phosphoprotein 1 (SPP1; also known as osteopontin), fibroblast growth factor 7 (FGF7), and prostaglandin E2 (PGE2) that aid in adhesion, proliferation, and implantation of the pig conceptus ( Fig. 1C and D) (Waclawik 2011, Bazer & Johnson 2014. Although PGR expression decreases in the uterine surface epithelium, expression is unchanged in the stromal fibroblast cells, deep glandular epithelium (dGE), and myometrium (Geisert et al 1994).…”

“…Transcripts for PTGS2 increase in uterine LE cells on day 12 of pregnancy and recombinant IL1β2 increased the expression of PTGS2 in endometrial explants that had activated NF-κB (Ashworth et al 2006, Mathew et al 2015. Prostaglandins, released by the conceptus and endometrium, have proinflammatory properties and essential functions during implantation (Kennedy et al 2007, Waclawik 2011, Seo et al 2014). …”

“…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. The combined spacio-temporal activities of these molecules on specific cell types within the endometrium set in motion a series of coordinated events that promote survival of the early pig conceptus (Bazer & Johnson 2014).…”

Identification of differentially expressed genes in the oviduct of two rabbit lines divergently selected for uterine capacity using suppression subtractive hybridization

“…Taking into account the steroid inactivation role of the HSD17B4 protein, we could hypothesize that overexpression of HSD17B4 in the oviduct of L-line rabbits could modify the estrogen concentration, changing the oviduct fluid composition and subsequently affecting the early embryonic development (Murray 1993;Killian 2004;Gad et al 2011). Similarly, changes in steroid concentration could also modify the expression of PGR, causing the desynchronization of oviductal and uterine environments and affecting the posterior development and implantation of embryos (Gad et al 2011;Waclawik 2011). ERO1L gene is involved in the "oxidation-reduction process".…”