Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review)

Abstract

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre-implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Preterm Birth and Subsequent Risk of Acute Childhood Leukemia: a Meta-Analysis of Observational Studies

“…Their observed results demonstrated that high birth weight was associated with increased risk of overall leukemia and ALL as well as AML. The hypothesis of the association between high birth weight and increased incidence of leukemia was based on two pieces of evidence: 1) significantly positive associations observed between insulin-like growth factors (IGFs) and many aspects of fetal growth; 2) the important role of IGFs in carcinogenesis [10,[34][35][36][37][38][39][40]. A previous experimental study demonstrated that IGF-1stimulation could promote the growth of lymphoid and myeloid cells [41].…”

Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ – an immunohistochemical study

“…11 On a cellular level, the effects of IGF-2 are similar to that of InsulinLike Growth Factor 1 (IGF-1) by promoting proliferation, differentiation, survival and migration of cells. 12,13 Functional versatility of IGF-2 must primarily be viewed within the context of IGF-axis, whose members such as Insulin-Like Growth Factor Binding Proteins (IGFBPs) and receptors IGF-1R and IGF-2R are involved in complex regulation of activity of both IGFs.…”

“…11,23 So far, the involvement of IGF-axis in embryonic and foetal development of human and animals has been relatively well investigated. 12,[24][25][26] In developing human tooth germs, IGF-axis has been implicated in amelogenesis and root formation, but there are only few accounts on particular members' roles (most notably IGF-1 and IGF-1R) during the earlier stages of tooth development. [27][28][29][30][31] On the other hand, involvement of PTEN in developing odontogenic tissues still remains to be investigated, even though the total mapping of PTEN expression patterns has been performed for developing human and mouse embryos.…”

The role of IGF-1 in neurodegenerative diseases

“…IGF-1 has also been identified as the predominant factor in fetal growth and development 5 . IGF-1 is necessary for both normal longitudinal bone growth and cortical bone mass accumulation …”