Impacts of Excessive Alpha-Tocopherol and Retinoic Acid on Cell Proliferation During Mouse and Placenta Development via CDKN1B Activation

Vitamins such as vitamin A and vitamin E are used in many therapeutics and cosmetics.They also play a vital role in fetal development during pregnancy.Therefore, this study aims to explore the negative effects of high doses of retinoic acid and alpha-tocopherol during embryo development and placentation.Fifteen pregnant mice were divided into three groups (n=5/group); (1) the control (received dimethyl sulfoxide (DMSO) and diluted with sunflower oil), (2) the Alpha-Toc treated (received 50 mg/kg/day dose), and (3) RA-treated (received 10 mg/kg/day dose).Intraperitoneal injections were given daily with a volume of 0.1 ml on gestational days 10.5, 11.5, and 12.5.The animals were euthanized by cervical dislocation on day 13.5 of gestation.Histological and immunolocalization of CDKN1B were performed.Histopathologically, the intestine, liver, and placenta were unaffected by Alpha-Toc; in contrast, RA caused severe malformations during histogenesis of the studied organs compared to a control group.Immunohistochemically, our findings revealed the upregulation of CDKN1B immunostaining by both Alpha-Toc and RA in varying proportions.We found that alpha-tocopherol and retinoic acid upregulated CDKN1B expression, which affected the histogenesis of the intestine, liver, and placenta, but via retinoic acid, not via alpha-tocopherol.