Postnatal expression of IGF2 is the norm in amniote vertebrates

Abstract

The insulin and insulin-like signalling (IIS) network plays an important role in mediating several life-history traits, including growth, reproduction and senescence. Although insulin-like growth factors (IGFs) 1 and 2 are both key hormones in the vertebrate IIS network, research on IGF2 in juveniles and adults has been largely neglected because early biomedical research on rodents found negligible IGF2 postnatal expression. Here, we challenge this assumption and ask to what degree IGF2 is expressed during postnatal life across amniotes by quantifying the relative gene expression of IGF1 and IGF2 using publicly available RNAseq data for 82 amniote species and quantitative polymerase chain reaction on liver cDNA at embryonic, juvenile and adult stages for two lizard, bird and mouse species. We found that (i) IGF2 is expressed postnatally across amniote species and life stages—often at a higher relative expression than IGF1 , contradicting rodent models; (ii) the lack of rodent postnatal IGF2 expression is due to phylogenetic placement, not inbreeding or artificial selection; and (iii) adult IGF2 expression is sex-biased in some species. Our results demonstrate that IGF2 expression is typical for amniotes throughout life, suggesting that a comprehensive understanding of the mechanisms mediating variation in life-history traits will require studies that measure both IGFs.

Overexpression of IGF2 affects mouse weight and glycolipid metabolism and IGF2 is positively related to macrosomia

“…The results of this study showed that compared with WT siblings, mice with IGF2 overexpression showed significant increase in weight at 5-10 weeks of age. Previous studies ( 14 , 24 ) reported that a sex bias exists in the expression of IGF2, and the IGF2 level in females is significantly higher than that in males at the age of 5 years. Moreover, another study ( 25 ) found that hypoxic conditions lead to the upregulation of IGF2 expression in the placenta of female fetuses, while the hypoxic placenta of male fetuses shows no change.…”

“…Based on previous studies, it was determined that IGF1 has high postnatal expression ( 29 , 30 ) and that the expression of IGF2 is high during embryonic development but decreases to an undetectable level after birth ( 30 – 32 ). Several recent studies ( 12 – 14 , 24 , 33 ) have suggested that IGF2 is also expressed postnatally in humans and may play an important role in growth and development. Due to the previous opinion, there is currently a lack of related research on human postnatal IGF2 compared to studies on postnatal IGF1 ( 24 ).…”

“…Several recent studies ( 12 – 14 , 24 , 33 ) have suggested that IGF2 is also expressed postnatally in humans and may play an important role in growth and development. Due to the previous opinion, there is currently a lack of related research on human postnatal IGF2 compared to studies on postnatal IGF1 ( 24 ). The present study constructed a mouse model of IGF2 overexpression, whose postnatal level of IGF2 was higher than that of WT mice, and the effects of IGF2 overexpression on the postnatal growth and glycolipid metabolism of the mice were explored, which might provide evidence for the postnatal effects of IGF2.…”

Evolution of Placental Hormones: Implications for Animal Models

“…Fetal growth is regulated by the insulin-like growth factor system with IGF2 as a key factor ( 67 ). IGF2 is expressed in the adults of most amniotes (reptiles, birds and mammals), including human ( 153 ), whereas in mouse and rat Igf2 is expressed in placenta but is largely absent in adults. Both IGF2 and the M6P/IGF2R receptor are imprinted genes in most mammals including marsupials ( 154 ).…”

Climate change and its effects on body size and shape: the role of endocrine mechanisms

“…IGF-2 has been much less studied than IGF-1 but is expressed pre-and postnatally across amniotes, often at higher levels of expression than IGF-1 [102], and can stimulate growth and metabolism [103]. We might anticipate that changes in circulating hormone levels in the insulin/insulin-like signalling network would promote changes in total…”