Fetal-maternal interactions during the establishment of pregnancy in ruminants.

Center for Animal Biotechnology and Genomics, Departments of Animal Science, Texas A&M University, College Station, Texas 77843, USA.
Society of Reproduction and Fertility supplement 02/2007; 64:379-96. DOI: 10.5661/RDR-VI-379
Source: PubMed

ABSTRACT This review integrates established information with new insights into molecular and physiological mechanisms responsible for events leading to pregnancy recognition, endometrial receptivity, and implantation with emphasis on sheep. After formation of the corpus luteum, progesterone acts on the endometrium and stimulates blastocyst growth and elongation to form a filamentous conceptus (embryo/fetus and associated extraembryonic membranes). Recurrent early pregnancy loss in the uterine gland knockout ewe model indicates that endometrial epithelial secretions are essential for peri-implantation blastocyst survival and growth. The elongating sheep conceptus secretes interferon tau (IFNT) that acts on the endometrium to inhibit development of the luteolytic mechanism by inhibiting transcription of the estrogen receptor alpha (ESR1) gene in the luminal (LE) and superficial ductal glandular (sGE) epithelia, which prevents estrogen-induction of oxytocin receptors (OXTR) and production of luteolytic prostaglandin F2-alpha pulses. Progesterone downregulates its receptors (PGR) in LE and then GE, correlating with a reduction of anti-adhesive MUC1 (mucin glycoprotein one) and induction of secreted LGALS15 (galectin 15) and SPP1 (secreted phosphoprotein one), that are proposed to regulate trophectoderm growth and adhesion. IFNT acts on the LE to induce WNT7A (wingless-type MMTV integration site family member 7A) and to stimulate LGALS15, CTSL (cathepsin L), and CST3 (cystatin C), which may regulate conceptus development and implantation. During the peri-implantation period, trophoblast giant binucleate cells (BNC) begin to differentiate from mononuclear trophectoderm cells, migrate and then fuse with the uterine LE as well as each other to form multinucleated syncytial plaques. Trophoblast giant BNC secrete chorionic somatomammotropin (CSH1 or placental lactogen) that acts on the endometrial glands to stimulate their morphogenesis and differentiated function. The interactive, coordinated and stage-specific effects of ovarian and placental hormones regulate endometrial events necessary for fetal-maternal interactions and successful establishment of pregnancy.

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    • "Testing this hypothesis requires the resolution of a number of challenges, including the ethical impossibility of obtaining human endometrium tissue samples during early pregnancy. The sheep, a species with epitheliochorial implantation, was considered to be a useful model to explore the physiological, molecular and biochemical events at the endometrial–extraembryonic membrane interface during early pregnancy (Spencer et al. 2007, Satterfield et al. 2009). In sheep, embryonic trophectoderm cells begin contact with the luminal endometrium epithelium between day 13 of pregnancy (P13) and P15 and then attach to endometrial cells on day 16, a process completed by day 22 post mating (Spencer et al. 2004). "
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    ABSTRACT: The expression and regulation of endometrial proteins are crucial for conceptus implantation and development. However, little is known about site-specific proteome profiles of the mammalian endometrium during the peri-implantation period. We utilised a two-dimensional gel electrophoresis/mass spectrometry-based proteomics approach to compare and identify differentially expressed proteins in sheep endometrium. Caruncular and intercaruncular endometrium were collected on days 12 (C12) and 16 (C16) of the oestrous cycle and at three stages of pregnancy corresponding to conceptus pre-attachment (P12), implantation (P16) and post-implantation (P20). Abundance and localisation changes in differentially expressed proteins were determined by western blot and immunohistochemistry. In caruncular endometrium, 45 protein spots (5% of total spots) altered between day 12 of pregnancy (P12) and P16 while 85 protein spots (10% of total spots) were differentially expressed between P16 and C16. In intercaruncular endometrium, 31 protein spots (2% of total spots) were different between P12 and P16 while 44 protein spots (4% of total spots) showed differential expression between C12 and C16. The pattern of protein changes between caruncle and intercaruncle sites was markedly different. Among the protein spots with implantation-related changes in volume, 11 proteins in the caruncular endometrium and six proteins in the intercaruncular endometrium, with different functions such as protein synthesis and degradation, antioxidant defence, cell structural integrity, adhesion and signal transduction, were identified. Our findings highlight the different but important roles of the caruncular and intercaruncular proteins during early pregnancy.
    Reproduction (Cambridge, England) 04/2014; 147(5-5):599-614. DOI:10.1530/REP-13-0600 · 3.26 Impact Factor
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    • "(Key Words: IFNT, Isoforms, ISG, MX, Uterus) approximately 20% of trophoblast cells form binucleate cells (Xie et al., 1996; Klisch et al., 2006) and attach to the uterine epithelium. A number of IFN-stimulated genes (ISGs), including the MX genes, are expressed in the uterus (Spencer et al., 2007; 2008). These ISGs are hypothesized to regulate endometrial receptivity to implantation as well as survival, growth, and development of the conceptus. "
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    ABSTRACT: Various endometrial genes in ruminant ungulates are regulated by conceptus interferon tau (IFNT). However, the effect of each IFNT isoform has not been carefully evaluated. In this study, the effects of 2 IFNT isoforms, paralogs found in utero, and interferon alpha (IFNA) on uterine epithelial and Mardin-Darby bovine kidney (MDBK) cells were evaluated. Expression vectors of the bovine interferon (bIFNT) genes bIFNT1, bIFNTc1, and bIFNA were constructed, and recombinant bIFNs (rbIFNs) were produced by 293 cells. Bovine uterine epithelial or MDBK cells were cultured in the presence or absence of increasing concentrations of each rbIFN for 24, 48, or 72 h. Transcript levels of the IFN-stimulated genes (ISGs) ISG12, ISG15, MX1, and MX2 were analyzed using quantitative reverse transcription-polymerase chain reaction. These messenger RNAs were up-regulated by rbIFN in a time- and concentration-dependent manner. In the epithelial cells, the ISG12 transcript level increased at 48 h after rbIFN treatment but slightly decreased at 72 h, whereas the transcript level of ISG15 increased at 24 h and was maintained through 72 h. Expressions of MX1 and MX2 increased at 72 h after rbIFN treatment. MX1 expression increased in all treatment groups, but MX2 increased only by bIFNTc1. In MDBK cells, the expression of ISG12 was increased by bIFNT1 and bIFNTc1 after 24 and 72 h; however, it was unchanged by rbIFNA. ISG15 increased following the same pattern as that seen in uterine epithelial cells, and MX1 showed a similar expression pattern. MX2 expression was increased by bIFNTc1 treatment in uterine epithelial cells, and its expression was increased by both bIFNT1 and bIFNTc1 in MDBK cells. These results show that epithelial and MDBK cell responses to IFNs differ, suggesting that IFNs possess common functions, but may have acquired different functions following gene duplication.
    Asian Australasian Journal of Animal Sciences 06/2013; 26(6). DOI:10.5713/ajas.2012.12529 · 0.56 Impact Factor
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    • "At the endometrial surface, adaptations are required to accommodate the implanting embryo (Aplin 1999, 2006), and these are highly species-specific, in concert with variations in depth of implantation. In human, mouse and rat, where implantation is interstitial and invasive, the epithelial barrier is transiently breached, then repaired, whereas in pig, sheep and camel, where there is interdigitation of placental and maternal cells without invasion, a stable, long-lived interface develops and the apical glycoprotein layer is modified to become pro-adhesive (Spencer et al. 2007). Glycoconjugate biosynthesis accounts for 1–2% of all genes in eukaryotes (Ohtsubo and Marth 2006). "
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    ABSTRACT: A family of 13 fucosyltransferase genes has evolved to catalyze the addition of fucose in various linkage positions to nascent glycoproteins. Null mutations in mice are unearthing unsuspected functions for glycoprotein fucosylation that affect embryo implantation and growth of the conceptus. Furthermore, as we show here, histological studies demonstrate that a variety of fucosylated structures are found within the glycan-rich interface between trophectoderm and uterine epithelium. We suggest that conservation or change in fucosyltransferase gene expression over evolutionary time has played a role in determining the stability of the maternal-fetal interface and therefore in shaping reproductive compatibility and, in turn, speciation.
    Glycobiology 04/2012; 22(4):470-8. DOI:10.1093/glycob/cwr156 · 3.75 Impact Factor