Placental Heat Shock Protein (HSP) Expression in Fetal Growth Restriction (FGR) Pregnancies: A Case-Control...

Fetal growth restriction (FGR) is frequently defined as the failure of the fetus to reach its genetically predetermined growth potential. Heat shock proteins (HSPs) are extreme-temperature-resistant molecules that help proteostasis. The aim of this prospective case-control immunohistochemistry study is to evaluate the expression of HSP90 and HSP70 in the placentas of pregnancies complicated with FGR and compare their levels with the control placentas of normal-growth pregnancies. A prospective case-control study was conducted including people undergoing singleton pregnancies who gave birth in a tertiary university hospital in Central Greece. Participants were divided into two equal groups: an FGR pregnancy group and a control group with normal growth. Immunohistochemistry of placental samples was assessed using anti-HSP90 alpha/beta antibody (clone F-8, Santa Cruz Biotechnology, Dallas, TX, USA) and anti-HSC70/HSP70 antibody (clone W27, sc-24, Santa Cruz Biotechnology, Dallas, TX, USA). A scoring system was created to quantify the expression of HSP90 and HSP70 in each sample, and the grade of staining was measured at four points. A total of 80 pregnant people were prospectively enrolled in our study, with 40 in each group. Both constitutive (HSP90β and HSC70/HSPA8) and stress-inducible (HSP90α and HSP70/HSPA1A/B) isoforms were analyzed. When comparing the total score of HSP expression, a statistically significant difference was observed for both HSP90 and HSP70. For HSP90 expression, only the Hofbauer cell's stain was identified as a statistically significant independent factor, meaning that its positive expression was observed in Hofbauer cells. For HSP70 expression, only the staining of syncytiotrophoblasts was identified as an independent factor. FGR is a common pregnancy complication and a leading cause of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide. Based on our findings, the lower expression levels of both HSP90 and HSP70 are associated with FGR, revealing a possible association with stress response in FGR pathophysiology. However, more robust data from larger-scale prospective studies are needed to elucidate the possible role of HSPs as potential FGR biomarkers.