Expression of Cripto-1 protein in placentas from term pregnancies with and without fetal growth restriction: a retrospective cohort study in Croatia.

OBJECTIVE: This study investigated Cripto-1 expression, a crucial regulator of epithelial-mesenchymal transition (EMT) and trophoblast differentiation, in term placentas from pregnancies complicated by fetal growth restriction (FGR), compared with healthy term placentas. We hypothesized that Cripto-1 expression is reduced in FGR placentas, reflecting impaired EMT. METHODS: A retrospective cohort study was conducted using 153 term placental samples collected between 2016 and 2020 at the Clinical Hospital Center Rijeka, Croatia. This study included 122 placentas from pregnant women with FGR and 31 placentas from gestational age-matched controls. Cripto-1 expression was evaluated using tissue microarrays and the immunohistochemical index was calculated by multiplying the staining intensity reaction by the percentage of positive cells. Clinical data were retrieved from medical records and included maternal age, parity, preeclampsia status, serum beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels, ultrasound fetal biometry, Doppler measurements of the umbilical artery and fetal circulation, fetal sex, weight, fetoplacental ratio, and placental histopathological findings. RESULTS: Maternal age, parity, and neonatal birth weight differed significantly between the FGR and control groups. However, no statistically significant differences in Cripto-1 expression were detected between the FGR and healthy placentas. Additionally, Cripto-1 expression was not associated with any of the clinical or biochemical parameters measured in the FGR group. CONCLUSION: Cripto-1 expression did not differ significantly between placentas with FGR, suggesting that its role may be more relevant in early placental development. Further studies are warranted to determine its value as an early biomarker of placental dysfunction.