Endocrine Abstracts

Introduction: Alterations in foetal growth lead to neonatal health risks and favour metabolic diseases during adult life. Therefore, the study of birth weight determination and its modifications is crucial for metabolic diseases prevention. Placental growth is a key factor in foetal growth. It has been suggested that insulin and the IGF system play an important role in foetal growth and placental development and function. Although, insulin and IGFs in the umbilical cord blood have been associated to birth weight, the roles of placental IGF1 and insulin receptors (IGF1R and IR), and the PI3K/Akt signalling pathway, shared by both receptors, are not fully elucidated. We aimed to analyse protein expression of insulin/IGF receptors and activation of the PI3K/Akt pathway in relation to placental weight and birth weight.

Methods: Transversal comparative study in placentas from healthy mothers of term newborns small gestational age (SGA), adequate gestational age (AGA), and large for gestational age (LGA) (n=20/group). Protein expression of IR, IGF1R, and phosphorylation of signalling molecules were analysed by western blot.

Results: IGF1R expression decreased 20% significantly in SGA compared to control AGA, and positively correlated with placental weight (r=0.34, P=0.007) and birth weight (r=0.285, P=0.027). IR protein expression was not modified between groups. Phosphorylation of PDK1, main kinase for Akt activation, decreased 40% in both SGA and LGA compared to control. In line with this, we observed a nearly 30% decrease in total Akt in SGA and LGA compared to AGA. PDK1-dependent phosphorylation pAkt–Thr308 showed a tendency, albeit not significant, to decrease in SGA and LGA, while pAkt–Ser273 did not differ between groups.

Conclusion: These results suggest PI3K/Akt pathway may be differentially regulated in SGA and LGA placentas, possibly related to decreased IGF1R expression in SGA, and perhaps other signalling pathways in LGA, consequently leading to alterations in birth weight.

Disclosure: This work was supported by the University of Guanajuato (0095/13), and FOMIX CONACYT – Guanajuato State Government (GTO-2012-C03-195238). M-L Lazo-de-la-Vega-Monroy was recipient of a postdoctoral fellowship scholarship from CONACYT (CVU: 217876).