Integrins and Extracellular Matrix Proteins at the Maternal-Fetal Interface in Domestic Animals

Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas 77843, USA.
Cells Tissues Organs (Impact Factor: 2.14). 02/2002; 172(3):202-17. DOI: 10.1159/000066969
Source: PubMed


Establishment of pregnancy in mammals requires coordinated conceptus-maternal interactions involving numerous hormones, growth factors and cytokines acting via specific receptors in the uterus. Uterine secretions play an important role in establishing synchrony between development of the conceptus and uterine receptivity, as well as in conceptus remodeling, adhesion, implantation and placentation in domestic species. Studies of non-invasive implantation in domestic livestock provide valuable opportunities to investigate fundamental processes of the initial events of apposition, attachment and adhesive interactions that are shared among species. In pigs and sheep, it appears that integrins play a dominant role in these fundamental processes via interactions with extracellular matrix molecules and other ligands to transduce cellular signals in uterine epithelial cells and conceptus trophectoderm. This review considers several of the potential integrin-binding ligands involved in the complex implantation adhesion cascade in pigs and sheep along with in vitro evidence for the transduction of cytoplasmic signals that may be required to sustain fetal and maternal contributions to the formation of the epitheliochorial placenta.

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    • "By linkage of the cytoskeleton to the cell cortex it influences the assembly of focal adhesion complexes [28] and E-cadherin dependent adherens junctions [29], or the integrity of microvilli [30]. Focal adhesion complexes and integrins play a major role in non-invasive implantation of livestock [31], besides cell fusion and microvilli integrity [24] [25]. It is known that microvilli contain active monomeric molecular forms of ezrin (linking the cytoskeleton with the cortex), but also oligomeric ezrin forms. "
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    ABSTRACT: The feto-maternal interface during bovine implantation was studied in vivo and using three-dimensional bovine endometrial (BCECph) and trophoblast spheroids (CCS), each with underlying fibroblasts. The expression of ezrin and cytokeratin 18 (CK18) was analyzed via immunohistochemistry (IHC), RT-PCR and western blotting in bovine endometrium (GD 18-44) with in vivo (VIVO) and in vitro-produced embryos (VITRO). BCECph were stimulated with cotyledon-conditioned media (CCM) and analyzed by TEM/SEM and IHC. CCS were stained (IHC) for TGC markers, to test if spheroidal trophoblast cells had differentiated into TGC. At GD 20, caruncular epithelium (CE) and uterine glands (UG) showed a loss of cytosolic ezrin and CK18 followed by a complete loss of both proteins. At GD 35 both reappeared in CE and UG. The endometrial expression pattern did not differ between VIVO and VITRO. RT-PCR and western blotting confirmed the presence of ezrin and CK18. All spheroids had an outer polarized, cytokeratin and ezrin positive epithelium (CE or trophoblast) with apical microvilli. Stimulation of BCECph with CCM induced similar changes in ezrin expression as observed in endometrial tissue. However, no ultrastructural alterations were found by transmission electron microscopy. Absence of TGC-specific glycoproteins in CCS indicated that TGC differentiation was not induced by three-dimensional culture conditions. Ezrin and CK18 are downregulated during implantation in cattle. The expression changes represent a temporal depolarization, which could be important for an establishment of bovine pregnancy. Our in vitro experiments demonstrate that the trophoblast could contribute to this change in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Placenta 06/2015; 36(8). DOI:10.1016/j.placenta.2015.06.001 · 2.71 Impact Factor
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    • "Both constitutive and cyclical expression of integrins has been observed in the uterus, and they are now considered to be the most decisive criteria for determining uterine receptivity (Lessey et al., 1996). Apical localization of ␣ V ␤ 3 and ␣ V ␤ 5 integrins in the mouse, human, baboon, rabbit, pig and sheep luminal epithelium makes these specific integrin pairs appropriate candidates for mediating trophoblast/epithelial interactions (Bowen et al., 1996; Lessey et al., 1996; Fazleabas et al., 1997; Burghardt et al., 2002; Illera et al., 2003). Moreover, the ␣ V ␤ 3 integrin has also been shown on the surface of the blastocyst (Sutherland et al., 1993), so a reciprocal and cooperative role in attachment is suggested. "
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    ABSTRACT: Summary Prenatal losses are a complex problem. Pregnancy requires orchestrated communication between the embryo and the uterus that includes secretions from the embryo to signal pregnancy recognition and secretion and remodelling from the uterine epithelium. Most of these losses are characterized by asynchronization between embryo and uterus. To better understand possible causes, an analysis was conducted of gene expression of a set of transcripts related to maternal recognition and establishment of rabbit pregnancy (uteroglobin, SCGB1A1; integrin α1, ITGA1; interferon-γ, IFNG; vascular endothelial growth factor, VEGF) in oviduct and uterine tissue at 16, 72 or 144 h post-ovulation and insemination. In the oviduct tissue, a significant decrease in the level of SCGB1A1 mRNA expression was observed from 144 h post-ovulation. In the case of ITGA1, the transcript abundance was initially lower, but mRNA expression increased significantly at 72 and 144 h post-ovulation. For IFNG, a huge decrease was observed from 16 to 72 h post-ovulation. Finally, no significant differences were observed in the VEGF transcript. For the endometrium, the results showed a significant decline in the level of SCGB1A1 mRNA expression from 16 to 144 h post-ovulation induction. The highest levels of ITGA1 transcript were detected at 144 h, followed by the 16 h group and lower at 72 h post-ovulation. For IFNG there were no significant differences among post-ovulation induction times. Finally, it was possible to observe that VEGF mRNA abundance was present at low levels at 16 h post-ovulation and remained low at 72 h, but increased at 144 h. The functional significance of these observations may provide new insights into the maternal role in prenatal losses.
    Zygote 11/2013; 23(02):1-9. DOI:10.1017/S0967199413000555 · 1.42 Impact Factor
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    • "At this interface there is also expression of multiple integrin subunits that potentially form heterodimeric receptors for SPP1 including ITGAV:ITGB3, ITGAV:ITGB1, ITGAV:ITGB5, and ITGA4:ITGB1 [21,35]. The interaction between the integrin heterodimers and SPP1 likely induces changes in morphology of trophectoderm and mediates adhesion between trophectoderm and uterine LE essential for implantation and placentation [34,93]. "
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    ABSTRACT: There is a dialogue between the developing conceptus (embryo-fetus and associated placental membranes) and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling, implantation, regulation of gene expression by uterine epithelial and stromal cells, placentation and exchange of nutrients and gases. The uterus provide a microenvironment in which molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph required for growth and development of the conceptus and receptivity of the uterus to implantation. Pregnancy recognition signaling mechanisms sustain the functional lifespan of the corpora lutea (CL) which produce progesterone, the hormone of pregnancy essential for uterine functions that support implantation and placentation required for a successful outcome of pregnancy. It is within the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. With proper placentation, the fetal fluids and fetal membranes each have unique functions to ensure hematotrophic and histotrophic nutrition in support of growth and development of the fetus. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. This review addresses the complexity of key mechanisms that are characteristic of successful reproduction in sheep and pigs and gaps in knowledge that must be the subject of research in order to enhance fertility and reproductive health of livestock species.
    Journal of Animal Science and Biotechnology 07/2012; 3(1):23. DOI:10.1186/2049-1891-3-23 · 1.68 Impact Factor
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