Selenium Attenuates HPV-18 Associated Apoptosis in Embryo-Derived Trophoblastic Cells but Not Inner Cell Mass In Vitro.
Objectives. Human papillomaviruses (HPV) are associated with cell cycle arrest. This study focused on antioxidant selenomethionine (SeMet) inhibition of HPV-mediated necrosis. The objectives were to determine HPV-18 effects on embryonic cells and to evaluate SeMet in blocking HPV-18 effects. Methods. Fertilized mouse embryos were cultured for 5 days to implanted trophoblasts and exposed to either control medium (group 1), HPV-18 (group 2), combined HPV-18 and 0.5 µM SeMet (group 3), or combined HPV-18 and 5.0 µM SeMet (group 4). After 48 hrs, trophoblast integrity and, apoptosis/necrosis were assessed using morphometric and dual-stain fluorescence assays, respectively. Results. HPV-18 exposed trophoblasts nuclei (253.8 ± 28.5 sq·µ) were 29% smaller than controls (355.6 ± 35.9 sq·µ). Supplementation with 0.5 and 5.0 µM SeMet prevented nuclear shrinkage after HPV-18 exposure. HPV-18 infected trophoblasts remained larger with SeMet supplementation. HPV-18 decreased cell viability by 44% but SeMet supplementation sustained cell viability. Apoptosis was lower when SeMet was present. HPV-18 decreased inner cell mass (ICM) viability by over 60%. Conclusions. HPV-18 decreased nuclear size and trophoblast viability but these effects were attenuated by the antioxidant SeMet. SeMet blocked HPV-18 associated apoptosis process in trophoblasts but not ICM cells suggesting involvement of different oxidative stress pathways.
Department of Gynecology and Obstetrics, 11370 Anderson Street, Suite 3950, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Jennifer A
JA
Tolen
Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, 11021 Campus Street, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Penelope
P
Duerksen-Hughes
Department of Gynecology and Obstetrics, 11370 Anderson Street, Suite 3950, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Kathleen
K
Lau
Department of Gynecology and Obstetrics, 11370 Anderson Street, Suite 3950, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Philip J
PJ
Chan