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RAGE Implications during DNA Double Strand Breaks in Trophoblast Cells

Intrauterine growth restriction (IUGR) is an obstetric pathology characterized by an increase in trophoblast apoptosis and decreased cell invasion. Trophoblasts are critical for a successful pregnancy and they mediate important steps such as implantation, immune protection of the fetus, maternal blood flow to the placenta, and delivery. Previous mouse studies in our laboratory showed increased trophoblast apoptosis, decreased cell invasion and increased placental receptors for advanced glycation end‐products (RAGE) during second hand smoke (SHS) treatment. More recently, a role for nuclear RAGE (nRAGE) has been implicated in DNA double strand break (DNA‐DSB) repair. We tested the hypothesis that RAGE is involved during DNA‐DSB repair in trophoblast cells. DSBs were induced in human trophoblasts (Bewo and Sw71) with cigarette smoke extract (CSE) or bleomycin (BLM). Assessment of nRAGE and g‐H2AX (involved in DNA‐DSB repair) was done by immunostaining. Invasion was measured in trophoblast cells after CSE and BLM treatment. Immunoblot was used to quantify nRAGE and g‐H2AX in cells. DNA degradation was used to determine DNA integrity.