Abstract
Establishment of pregnancy in pigs involves maintaining progesterone secretion from the corpora lutea in addition to regulating a sensitive interplay between the maternal immune system and attachment of the rapidly expanding trophoblast for nutrient absorption. The peri-implantation period of rapid trophoblastic elongation followed by attachment to the maternal uterine endometrium is critical for establishing a sufficient placental-uterine interface for subsequent nutrient transport for fetal survival to term, but is also marked by the required conceptus release of factors involved with stimulating uterine secretion of histotroph and modulation of the maternal immune system. Many endometrial genes activated by the conceptus secretory factors stimulate a tightly controlled proinflammatory response within the uterus. A number of the cytokines released by the elongating conceptuses stimulate inducible transcription factors such as nuclear factor kappa B (NFKB) potentially regulating the maternal uterine proinflammatory and immune response. This review will establish the current knowledge for the role of conceptus cytokine production and release in early development and establishment of pregnancy in the pig.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-1891-5-51) contains supplementary material, which is available to authorized users.
Highlights
Establishment of pregnancy by the pre-implantation porcine conceptuses requires extending the lifespan and progesterone secretion from the corpora lutea (CL) and appropriately contributing to the intricate interplay between the maternal immune system and attachment of the rapidly expanding trophoblast
Establishment of a receptive endometrium for conceptus attachment is regulated through progesterone induction of epithelial progesterone receptor (PGR) loss allowing finely synchronized alterations in the Luminal epithelium (LE) extracellular matrix exposing attachment factors such as transmembrane integrin heterodimer receptors and release of the matricellular protein, secreted phosphoprotein 1 (SPP1; referred to as osteopontin) [3,31] and balanced secretion of numerous growth factors, cytokines, prostaglandins, enzymes and their inhibitors which are enhanced by conceptus estrogen synthesis and release during the peri-implantation period [11,27,32]
Expansion of the conceptuses throughout the uterine horns provides the mechanism for estrogen to cover the uterine surface for maternal recognition of pregnancy, initiate trophoblast attachment to the LE and regulate the maternal lymphocyte response to conceptus IFNs which stimulate vascular changes and increases angiogenesis for the proper microenvironment for placentation
Summary
Establishment of pregnancy by the pre-implantation porcine conceptuses (embryo and extraembryonic membranes) requires extending the lifespan and progesterone secretion from the corpora lutea (CL) and appropriately contributing to the intricate interplay between the maternal immune system and attachment of the rapidly expanding trophoblast. Conceptus secretion of IFNG increases immediately following trophoblast elongation in the pig [117], suggesting that the conceptuses may induce endometrial IL18 release to assist in development and placental attachment during early pregnancy. The loss of conceptus IL1B2 stimulation and switch to endometrial IL18 production during placental attachment in the pig would decrease the potential pro-inflammatory stimulation of the conceptuses following trophoblast elongation which maybe important to control cytokine and immune functions following implantation [122]. Pig conceptuses secrete estrogen during the periimplantation period of pregnancy which increases uterine LE expression of interferon regulatory factor 2 (IRF2), a transcriptional repressor of classical IFN-stimulated genes, which would restrict IFNG and IFND stimulation to the underlying stroma. With the abrupt decline in conceptus expression of IL1B2 following rapid elongation, there is a tremendous increase in the filamentous conceptus trophoblastic expression of
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