Insulin-Like Growth Factor-I Messenger Ribonucleic Acid in the Developing Human Placenta and in Term Placenta of Diabetics

Abstract

Fetal growth and development are dependent upon the growth and development of the placenta. Control of placental growth and development is little understood. Immunoreactive insulin-like growth factor-I and -II (IGF-I and IGF-II) have been shown to be released by human placental tissue and human placental membranes have been observed to contain specific receptors for these growth factors. Furthermore, we have demonstrated the presence of IGF-II mRNA transcripts in the developing human placenta and at gestational term in placentae of diabetics. Thus, the IGFs may have a regulatory role in the growth and development of the placenta via autocrine and/or paracrine mechanism(s) of action. In this report we demonstrate the presence of four differing size species of placental poly(A)+ RNA which specifically hybridize to an IGF-I probe originally isolated from an adult human liver cDNA library and localize IGF-I and IGF-II mRNA to syncytiotrophoblasts and fibroblasts, respectively, of the placenta by in situ hybridization. The major transcript is 7500 bases in size and the remaining three transcripts are 5000, 1100, and 900 bases in length with no apparent changes from these sizes throughout gestation and at term in diabetics. Quantification by densitometry of placental IGF-I mRNA detected by dot blot hybridization indicated that first and second trimester placentae each express more IGF-I mRNA relative to that expressed in placenta at term. These results suggest that there are developmental changes in the relative amount of IGF-I mRNA expressed in the human placenta. IGF-I is, therefore, most likely important early in gestation as a placental growth factor. This time period is critical for fetal development and growth, when embryonic induction, organogenesis, and rapid cell proliferation occur.

Altered Placental and Fetal Expression of IGFs and IGF-Binding Proteins Associated With Intrauterine Growth Restriction in Fetal Sheep During Early and Mid-Pregnancy

“…During early and mid gestation, the placental expression of IGF-I mRNA is greater than in late pregnancy (24,25), suggesting that IGF-I plays an important role in early placental development as a placental growth factor (25). Placental IGF-I expression is mainly localized to the maternal stroma (12), and although statistical comparison between the two tissue types is not possible, our data support previous localization observations.…”

Maternal‐placental insulin‐like growth factor (IGF) signaling and its importance to normal embryo‐fetal development

“…Although not all reports are consistent, in the baboon, rhesus monkey, and human, the IGF-1R, IGF-1, and IGF-2 have all been localized to the cellular layers of placenta, including the continuous layer of cytotrophoblasts, the protective barrier layer of multi-nucleated syncytiotrophoblasts, and to the maternal decidual membranes, depending on the stage of gestation (Coulter and Han, 1996;Dhara et al, 2001;Han et al, 1996;HildPetito et al, 1994;Wang et al, 1988). Maternal IGF-1 and IGF-2 levels change only modestly if at all throughout gestation Tarantal and Gargosky, 1995), except during implantation when maternal IGF-2 levels increase dramatically (Dhara et al, 2001).…”

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

“…Both IGFs-I and -II are synthesized in the placenta (6,7). As the localization of IGFs and IGFBPs was similar, it was suggested that the IGFBPs regulated IGFs within the placenta (8).…”