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. 2013 Jun 26;4(1):23.
doi: 10.1186/2049-1891-4-23.

Pregnancy recognition signaling mechanisms in ruminants and pigs

Fuller W Bazer  1
Affiliations

Pregnancy recognition signaling mechanisms in ruminants and pigs

Fuller W Bazer. J Anim Sci Biotechnol. .

Abstract

Maternal recognition of pregnancy refers to the requirement for the conceptus (embryo and its associated extra-embryonic membranes) to produce a hormone that acts on the uterus and/or corpus luteum (CL) to ensure maintenance of a functional CL for production of progesterone; the hormone required for pregnancy in most mammals. The pregnancy recognition signal in primates is chorionic gonadotrophin which acts directly on the CL via luteinizing hormone receptors to ensure maintenance of functional CL during pregnancy. In ruminants, interferon tau (IFNT) is the pregnancy recognition signal. IFNT is secreted during the peri-implantation period of pregnancy and acts on uterine epithelia to silence expression of estrogen receptor alpha and oxytocin receptor which abrogates the oxytocin-dependent release of luteolytic pulses of prostaglandin F2-alpha (PGF) by uterine epithelia; therefore, the CL continues to produce progesterone required for pregnancy. Pig conceptuses secrete interferon delta and interferon gamma during the peri-implantation period of pregnancy, but there is no evidence that they are involved in pregnancy recognition signaling. Rather, pig conceptuses secrete abundant amounts of estrogens between Days 11 to 15 of pregnancy required for maternal recognition of pregnancy. Estrogen, likely in concert with prolactin, prevents secretion of PGF into the uterine venous drainage (endocrine secretion), but maintains secretion of PGF into the uterine lumen (exocrine secretion) where it is metabolized to a form that is not luteolytic. Since PGF is sequestered within the uterine lumen and unavailable to induce luteolysis, functional CL are maintained for production of progesterone. In addition to effects of chorionic gonadotrophin, IFNT and estrogens to signal pregnancy recognition, these hormones act on uterine epithelia to enhance expression of genes critical for growth and development of the conceptus.

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Figures

Figure 1
Figure 1
Interferon tau (IFNT) is the pregnancy recognition hormone in sheep and other ruminants that acts to silence expression of estrogen receptor alpha (ESR1) and, in turn, oxytocin receptor (OXTR) to prevent development of the luteolytic mechanism that required oxytocin (OXT) from the corpus luteum (CL) and posterior pituitary to induce luteolytic pulses of prostaglandin F2α (PGF). Thus, IFNT blocks the ability of the uterus to develop the luteolytic mechanism, but does not inhibit prostaglandin synthase 2 (PTGS2) or the basal production of PGF during pregnancy.
Figure 2
Figure 2
Silencing expression of progesterone receptor (PGR) in uterine epithelia is a prerquisite for implantation in mammals. Therefore, progesterone (P4) acts via PGR-positive uterine stromal cells to increase expression of progestamedins, e.g. fibroblast growth factor-7 (FGF7) and FGF10, as well as hepatocyte growth factor (HGF) in sheep uteri. The progestamedins, as well as interferon tau (IFNT) exert paracrine effects on uterine epithelia and conceptus trophectoderm that express receptors for FGF7 and FGF10 (FGFR2IIIb) and HGF (MET) to stimulate cell signaling pathways including phosphatidyl inositol kinase 3 kinase (PI3K) and mitogen activated protein kinase (MAPK) to stimulate gene expression and secretory responses by trophectoderm and uterine luminal (LE) and superficial glandular (sGE) epithelia that do not express signal transducers and activators of transcription (STAT1/STAT2). Thus, IFNT activates undefined alternate cell signaling pathways that may include PI3K and MAPK to influence gene expression by uterine LE and sGE.
Figure 3
Figure 3
The theory of pregnancy recognition in the pig is that secretion of prostaglandin F2α (PGF) is endocrine, that is, toward the uterine vascular drainage to induce luteolysis in cyclic pigs. However, PGF is secreted in an exocrine direction, that is, toward the uterine lumen in pregnant pigs where it is metabolized and unavailable to exert luteolytic effects.
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