The Outer Membrane Protein Tp92 of Treponema pallidum Induces BeWo Cells Apoptosis and Oxidative Stress via the Nrf2/keap1 Pathway

Treponema pallidum can be transmitted from the mother to the newborn via the placenta. Pregnancy complications that can arise from this include congenital syphilis, stillbirth, miscarriage, preterm birth, and fetal growth limitation. Tp92 is a protein located in the outer membrane of T.pallidum and has a β-barrel structure. The structural features of this protein are similar to those of other outer membrane proteins found in Gram-negative bacteria. It plays a crucial role in the initial infection of T. pallidum. However, the precise function of Tp92 in placental trophoblast cells remains uncertain. BeWo cells, derived from human choriocarcinoma, are commonly used to model placental trophoblast cells. Their physical structure and chemical composition are similar to undifferentiated trophoblasts. Our study revealed that Tp92 induces apoptosis in BeWo cells through various mechanisms, including reducing cell survival, decreasing mitochondrial membrane potential, increasing the number of TUNEL-positive cells, enhancing caspase-3 and 7 activity, and upregulating Bax and cleaved caspase-3 proteins. Additionally, Tp92 raises reactive oxygen species (ROS) and malondialdehyde levels, decreases superoxide dismutase (SOD) activity, and inhibits Nrf2 translocation to the nucleus, leading to reduced expression of Nrf2-regulated genes HO-1, NQO1, and SOD-1. Activation of the Nrf2/Keap1 pathway with the Nrf2 activator TBHQ can restore its function and inhibit apoptosis. This reveals that Tp92 induces oxidative stress and cell death by increasing ROS and inhibiting the Nrf2 pathway, offering a potential therapeutic target for pregnancy and congenital syphilis.