Gestational Pyrethroid Exposure and Placental Health in Wistar Rats: Evaluation of Epigenetic, Developmental, and Oxidative Stress Biomarkers
Anja Katić, Marta Himelreich Perić, Dajana Krsnik, Petra Petrina, Marko Hohšteter, Suzana Žunec, Dubravka Rašić, Vedran Micek, Marijana Neuberg, Goran Kozina, Ana Lucić Vrdoljak, Ana Katušić BojanacUnderstanding the mechanisms of placental toxicity provides an important research tool that can help to clarify how early-life exposure may influence adverse pregnancy outcomes, foetal health, and long-term disease risk in adulthood. In the present study we estimated the effects of oral gestational exposure to the pyrethroid insecticide α-cypermethrin (α-cyp), a potential endocrine disruptor, in doses of 1, 10, and 19 mg/kg bw/day on different parameters in placentas of Wistar rats (n = 5 per group; 30 animals in total). We evaluated global DNA methylation within the LINE1 repetitive region using the pyrosequencing method and assessed developmental parameters by immunohistochemical and histopathological analyses and changes in placental weight and oxidative stress biomarkers by high-performance liquid chromatography and spectrophotometry. Global DNA methylation percent decreased dose-dependently, although not significantly. In contrast, a significant decrease in proliferation in placental trophoblast giant cells was observed after exposure to 10 and 19 mg α-cyp/kg bw/day. No significant changes in apoptosis, placental histopathology, placental weight or the examined oxidative stress parameters were observed. These findings suggest that gestational α-cyp exposure may affect placental development through reduced trophoblast giant cell proliferation and subtle epigenetic alterations, in the absence of overt histopathological or oxidative changes. Further studies are warranted to determine the molecular mechanisms underlying these responses and their potential implications for placental function and foetal development.