Osteopontin: Roles in Implantation and Placentation1

Abstract

Osteopontin (OPN) is an acidic member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of extracellular matrix proteins/cytokines that undergoes extensive posttranslational modification, including phosphorylation, glycosylation, and cleavage, yielding molecular mass variants ranging in size from 25 to 75 kDa. The result is a versatile protein(s) with multiple functions arising from its role as a mediator of cell-cell and cell-extracellular matrix (ECM) communication that encompass both normal and tumorigenic developmental processes, immunological responses during inflammation and wound healing, and biomineralization. Studies in primates, pigs, sheep, and rodents have revealed that OPN is a major constituent of the uterine-placental microenvironment with influence as 1) a component of histotroph required for adhesion and signal transduction at the uterine-placental interface throughout pregnancy, 2) a gene product expressed by uterine stroma contributing to a decidualization-like transformation that correlates with the degree of conceptus invasiveness, and 3) a product of resident uterine and placental immune cells that may regulate their behavior and cytokine production. This minireview summarizes information regarding uterine and placental expression of OPN that has accumulated over the past 15 yr, and we briefly describe structural/functional properties of this protein that are likely relevant to its role(s) during pregnancy. Comparative studies have offered insights into the potential hormonal/cytokine, cellular, and molecular mechanisms underlying OPN-mediated adhesion, remodeling, and cell-cell/cell-ECM communication within the uterus and placenta. OPN has the potential to profoundly impact pregnancy, and investigators are now challenged to focus on the mechanistic nature of the functions of this multifaceted and major component of the uterine-placental microenvironment.

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

“…It is a glandular secretory protein that functions during implantation in the extracellular matrix as a mediator of cell-to-cell adhesion and cell migration during trophoblast attachment (Johnson et al 2003). There is much evidence to suggest that SPP1 mRNA expression is regulated by progesterone and does not appear to be influenced by IFNT in the ovine endometrium (see review by Johnson et al 2003).…”

“…It is a glandular secretory protein that functions during implantation in the extracellular matrix as a mediator of cell-to-cell adhesion and cell migration during trophoblast attachment (Johnson et al 2003). There is much evidence to suggest that SPP1 mRNA expression is regulated by progesterone and does not appear to be influenced by IFNT in the ovine endometrium (see review by Johnson et al 2003). Progesterone control was not indicated in the present study and a recent report suggested that SPP1 was regulated independently of pregnancy, IFNT and progesterone in an ovine cell culture system (Ahn et al 2009).…”

Implantation mechanisms: insights from the sheep

“…They play a dominant role in interactions with ECM to transduce cellular signals in uterine epithelial cells and conceptus trophoblast , Johnson et al 2003a. The central role of integrins in the implantation adhesion cascade is to bind ECM ligand(s) to cause cytoskeletal reorganization, stabilize adhesion, and mediate cell migration, proliferation and differentiation through numerous signaling intermediates (Giancotti & Ruoslahti 1999).…”

Detection of osteopontin on Holstein bull spermatozoa, in cauda epididymal fluid and testis homogenates, and its potential role in bovine fertilization

“…More recently it has been detected in many tissues and fluids, including urine (Sorenson et al 1995), milk (Sorensen & Petersen 1993, Sorensen et al 2003, kidney (Xie et al 2001), uterine endometrium of rabbits (Apparao et al 2003), sheep (Johnson et al 2003, Kimmins et al 2004, cows (Kimmins et al 2004) and pigs (Garlow et al 2002), the bovine oviduct (Gabler et al 2003), and on the luminal surfaces of epithelial cells of human gastrointestinal and reproductive tracts, gall bladder, pancreas, lung, breast, urinary tract, salivary glands, and sweat glands (Brown et al 1992). OPN may be glycosylated, phosphorylated and sulfated, and its expression and post-translational modifications are tissue-specific and regulated by many hormones and growth factors (Denhardt & Guo 1993).…”