Pregnancy-Specific Alterations in the Expression of the Insulin-Like Growth Factor System during Early Placental Development in the Ewe¹

Abstract

The placenta is recognized as an important determinant of fetal growth rate, yet the factors regulating its proliferation remain poorly understood. Components of the insulin-like growth factor (IGF) system were localized in the ovine uterus using in situ hybridization between days 13-55 of gestation, the period of implantation and placentome formation. IGF-II messenger RNA (mRNA) expression was intense in the fetal mesoderm, particularly at the tips of the invading placentome villi. Moderate levels of IGF-II mRNA were also observed in the maternal caruncular stroma. In contrast, expression of IGF-1 mRNA was low (compared to estrous levels) and ubiquitous decreasing as gestation advanced. IGF-binding protein-2 (IGFBP-2 mRNA was not detected until day 29 of gestation, when it appeared restricted to the dense caruncular-like stroma lining the luminal epithelium, colocalized with IGFBP-4. High concentrations of IGFBP-4 mRNA expression were also found in the placentome capsule. IGFBP-3 mRNA expression was intense in the luminal epithelium between days 13-15 of gestation. Subsequently, levels in this region dropped significantly (P < 0.001). IGFBP-3 mRNA expression was also high in the maternal placentome villi, where photographic emulsions localized expression to blood vessel walls. Peak expression of IGF type 1 receptor (IGF-1R) mRNA was found in the deep uterine glands, with intermediate expression in the superficial uterine glands. Moderate expression of IGF-1R mRNA was initially recorded in caruncular stroma, but levels in this region decreased significantly (P < 0.001) to below the detection limit of the technique after interdigitation by the fetal allantochorion. Furthermore, IGF-1R mRNA could not be detected in any fetal placentome tissue. This study, therefore, has established the pattern of expression of the IGFs, IGF-1R, and three of the IGFBPs during establishment of the ovine placenta. It will form the basis for future work to investigate how this system is regulated and to determine the role of the IGFs in placental development.

Ergot alkaloid exposure during gestation alters. I. Maternal characteristics and placental development of pregnant ewes1

“…Reductions in IGF1 concentrations are associated with glucose insufficiency in ewes, which results in a shift in nutrient partitioning (Tygesen et al, 2008). Although intact IGF1 does not cross the placenta, increases in IGF1 concentrations may stimulate placental growth through IGF1 receptors (Browne and Thorburn, 1989;Reynolds et al, 1997). Such a compensatory response in IGF1 levels after switching from E+ to E− treatment may be an attempt to stimulate placental development and rescue fetal growth.…”

The Kangaroo Cation-independent Mannose 6-Phosphate Receptor Binds Insulin-like Growth Factor II with Low Affinity

“…IGF-II is a polypeptide mitogen related to insulin that is believed to be particularly important during placental and embryonic development (3)(4)(5)(6). The binding sites for IGF-II and mannose 6-phosphate-bearing ligands have been shown to be distinct (7)(8)(9).…”

Mating Season Influences Placental Characteristics, Plasma IGF Concentration, and mRNA Expression without Affecting Lamb Birth Weight in Akkaraman Ewes

“…Terefore, examining the post-natal development and adult productivity of lambs obtained from ewes mating in different seasons can be an essential contributor to revealing the efects of seasonal diferences in placental characteristics on the productivity of animals in the adult period. Previous studies have reported that IGFs are expressed and secreted by the sheep uterus and placenta [48,49]. IGF-I and IGF-II mRNAs were detected in sheep embryos throughout pre-implantation development from the singlecell stage to the blastocyst stage [50].…”

“…IGF-I and IGF-II mRNAs were detected in sheep embryos throughout pre-implantation development from the singlecell stage to the blastocyst stage [50]. Following implantation, maternal uterine IGF-I mRNA expression was low, making it unlikely that locally expressed and produced IGF-I is essential for placental development [49]. In contrast, expression of IGF-II mRNA in the placentome capsule and endometrial stroma continued throughout the frst half of pregnancy, and IGF-II mRNA expression increased in foetal mesodermal tissues from days 14 to 35 and remained elevated until birth [51].…”