Placental Heat Shock Protein (HSP) Expression in Fetal Growth Restriction (FGR) Pregnancies: A Case–Control Immunohistochemistry Study

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.