Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458 USA.
Department of Animal Science, Texas A&M University, College Station, TX 77843 USA.
J Anim Sci Biotechnol. 2014 Dec 17;5(1):56. doi: 10.1186/2049-1891-5-56. eCollection 2014.
Osteopontin (OPN; also known as Secreted Phosphoprotein 1, SPP1) is a secreted extra-cellular matrix (ECM) protein that binds to a variety of cell surface integrins to stimulate cell-cell and cell-ECM adhesion and communication. It is generally accepted that OPN interacts with apically expressed integrin receptors on the uterine luminal epithelium (LE) and conceptus trophectoderm to attach the conceptus to the uterus for implantation. Research conducted with pigs and sheep has significantly advanced understanding of the role(s) of OPN during implantation through exploitation of the prolonged peri-implantation period of pregnancy when elongating conceptuses are free within the uterine lumen requiring extensive paracrine signaling between conceptus and endometrium. This is followed by a protracted and incremental attachment cascade of trophectoderm to uterine LE during implantation, and development of a true epitheliochorial or synepitheliochorial placenta exhibited by pigs and sheep, respectively. In pigs, implanting conceptuses secrete estrogens which induce the synthesis and secretion of OPN in adjacent uterine LE. OPN then binds to αvβ6 integrin receptors on trophectoderm, and the αvβ3 integrin receptors on uterine LE to bridge conceptus attachment to uterine LE for implantation. In sheep, implanting conceptuses secrete interferon tau that prolongs the lifespan of CL. Progesterone released by CL then induces OPN synthesis and secretion from the endometrial GE into the uterine lumen where OPN binds integrins expressed on trophectoderm (αvβ3) and uterine LE (identity of specific integrins unknown) to adhere the conceptus to the uterus for implantation. OPN binding to the αvβ3 integrin receptor on ovine trophectoderm cells induces in vitro focal adhesion assembly, a prerequisite for adhesion and migration of trophectoderm, through activation of: 1) P70S6K via crosstalk between FRAP1/MTOR and MAPK pathways; 2) MTOR, PI3K, MAPK3/MAPK1 (Erk1/2) and MAPK14 (p38) signaling to stimulate trohectoderm cell migration; and 3) focal adhesion assembly and myosin II motor activity to induce migration of trophectoderm cells. Further large in vivo focal adhesions assemble at the uterine-placental interface of both pigs and sheep and identify the involvement of sizable mechanical forces at this interface during discrete periods of trophoblast migration, attachment and placentation in both species.
骨桥蛋白 (OPN; 也称为分泌性磷蛋白 1, SPP1) 是一种分泌型细胞外基质 (ECM) 蛋白，可与多种细胞表面整合素结合，刺激细胞-细胞和细胞-ECM 黏附与通讯。人们普遍认为，OPN 与子宫腔上皮 (LE) 和胚胎滋养层表面表达的顶端整合素受体相互作用，将胚胎附着在子宫上进行着床。通过利用妊娠延长的植入前阶段，猪和绵羊的研究显著推进了对 OPN 在着床过程中作用的理解，在这个阶段，伸长的胚胎在子宫腔内自由生长，需要在胚胎和子宫内膜之间进行广泛的旁分泌信号传递。随后，胚胎滋养层逐渐附着到子宫 LE 上，形成真正的上皮绒毛膜或上皮-绒毛膜胎盘，这分别是猪和绵羊的特征。在猪中，着床胚胎分泌雌激素，诱导相邻子宫 LE 中 OPN 的合成和分泌。然后，OPN 与滋养层上的 αvβ6 整合素受体以及子宫 LE 上的 αvβ3 整合素受体结合，将胚胎附着到子宫 LE 上进行着床。在绵羊中，着床胚胎分泌干扰素 tau，延长黄体的寿命。黄体释放的孕激素随后诱导子宫内膜 GE 中的 OPN 合成和分泌到子宫腔中，OPN 与滋养层上表达的整合素 (αvβ3) 和子宫 LE (具体整合素未知) 结合，将胚胎附着到子宫上进行着床。OPN 与绵羊滋养层细胞上的 αvβ3 整合素受体结合，通过以下方式诱导体外粘着斑组装，这是滋养层粘着和迁移的先决条件：1) 通过 FRAP1/MTOR 和 MAPK 途径之间的串扰激活 P70S6K；2) MTOR、PI3K、MAPK3/MAPK1 (Erk1/2) 和 MAPK14 (p38) 信号传导，刺激滋养层细胞迁移；3) 粘着斑组装和肌球蛋白 II 运动活性，诱导滋养层细胞迁移。在猪和绵羊的子宫-胎盘界面也进一步组装了较大的体内粘着斑，并确定了在这两个物种的滋养层迁移、附着和胎盘形成的特定时期，在这个界面涉及到相当大的机械力。
