Fetal macrosomia and placental expression of fibroblast growth factor 21 and peroxisome proliferator-activated receptor alpha

Macrosomia (birth weight >4000 g) is a product of endocrine dysfunction in utero leading to fetal overgrowth and can lead to maternal and infant morbidity. Fibroblast growth factor 21 (FGF21) and its transcription factor, peroxisome proliferator-activated receptor alpha (PPARα), are found in the placenta and are associated with abnormal metabolic states. Their relationship to the placental dysregulation that leads to macrosomia is unknown. We sought to evaluate the relationship between protein expression of FGF21 and PPARα in placental samples from infants with macrosomia compared to controls (<4000 g) on both the maternal and fetal sides of the placenta. Placental specimens were collected at the time of delivery and protein levels of FGF21 and PPARα were quantified <i>via</i> Western Blot analysis and normalized to GAPDH. Student's <i>t</i>-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Chi-squared analysis, and Spearman's correlation were used for statistical analyses. Baseline characteristics were similar across both groups. FGF21 and PPARα levels on the maternal side of the placenta did not differ based on presence of macrosomia. PPARα expression was statistically significantly lower on the fetal side in infants with macrosomia. In controls alone, FGF21 and PPARα trended lower on the maternal side compared to the fetal side although this was not statistically significant. PPARα and FGF21 were positively correlated throughout the placenta. We found that lower PPARα expression on the fetal side of placenta was noted in infants with macrosomia, identifying a possible contribution to the growth discrepancy in this group. PPARα and FGF21 are strongly correlated in the human placenta.