Endocrine Abstracts

JOINT1191

Background/Objective: Foetal growth involves a complex interplay of molecular systems, including the insulin/insulin-like growth factor (IGF) system, adiponectin, and peroxisome proliferator-activated receptors (PPARs) signalling pathways. This study aimed to investigate the expression and abundance of a subset of genes and proteins associated with these pathways in placental tissue and cord blood collected from small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), and large-for-gestational-age (LGA) infants, as well as associated first-trimester maternal serum.

Methods: A total of 55 LGA-, 61 SGA-, and 109 AGA-born infants were included in the study. RT-qPCR was employed to analyse placental tissue samples collected at term, focusing on differential expression of 22 key genes, including IGF1, IGF2, IGF1R, IGF2R, INSR, IGFBP1-7, PPARA, PPARB, PPARG, RXRA, RXRB, ADIPOQ, ADIPOR1, ADIPOR2, APPL1, and APPL2. A blinded assessor evaluated a subset of placental samples (n=78) using semi-quantitative IHC analysis to validate differential gene expression at the protein level. ELISA was utilised to measure the abundance of chosen proteins (IGF1, IGF2, sIGF2R, IGFBP2, PAPP-A) in first-trimester maternal serum samples, as well as four proteins (IGF1, IGF2, sIGF2R, IGFBP2) in cord blood samples collected at term.

Results: The expression of placental genes IGF1, IGF2, IGF2R, IGFBP2, and PPARA varied among the three groups, with significant findings for IGF1, IGF2, and PPARA after multiple testing corrections. No meaningful expression of ADIPOQ was observed. With IHC analysis, strong expression of IGF1, IGF2, IGF2R was observed in the LGA group compared to the SGA and AGA groups. Strong expression of PPARA was observed in the LGA group compared to the SGA group. Weak expression of IGFBP2 was observed in both the LGA and AGA groups compared to the SGA group, with weaker expression in the LGA group compared to the AGA group. A strong positive correlation was found between cord blood IGF1 and infant birth weight (rs =0.73, P <0.001), and a strong negative correlation with IGFBP2 (rs =−0.56, P <0.001). A modest positive correlation was observed for IGF2 (rs =0.42, P <0.001). No associations were found between maternal serum protein levels and infant phenotype.

Conclusion: This study shows for the first time in humans an association between PPARA and foetal birth weight and confirms the association between the IGF signalling pathway and birth weight.