(829.2) Decreased Placental mTOR Signaling And Increased Placental Apoptosis Are Associated With Secondhand Smoke (SHS)-Induced Intrauterine Growth Restriction (IUGR) In Mice

Poster Board Number: D52

Zoe Bell (Brigham Young University), Joe Kiehl (Brigham Young University), Derek Clarke (Brigham Young University), Katrina Curtis (Brigham Young University), Paul Reynolds (Brigham Young University), Juan Arroyo (Brigham Young University)

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with maternal, fetal, and placental abnormalities, but studies investigating the inducibility of IUGR by secondhand smoke (SHS) are limited. The mTOR pathway regulates protein expression and cell growth. Disrupted mTOR signaling and apoptosis are associated with the development of several obstetric complications including IUGR. We tested the hypothesis that SHS exposure disrupts the mTOR pathway and apoptosis in mice. C57Bl6 mice were exposed to SHS for 4 days from day 14 to day 17 of gestation (dGA). At the time of necropsy (18 dGA) placental and fetal weights were recorded and tissues were immediately frozen for immunoblot analysis. Mice exposed to SHS demonstrated a significant reduction in fetal weight (7.35-fold; p≤0.0001) and placental weight (1.13-fold; p≤0.0001) compared to controls. Significant decreases were observed for placental activation of mTOR (2.1-fold; plt;0.03), p70 (1.9-fold; p,0.03) and 4EBP1 (1.3-fold (plt;0.03) in IUGR placentas compared to controls. Increased placental active caspase 3 (1.1-fold; plt;0.04) and the antiapoptotic placental XIAP protein (2.2-fold; plt;0.03) were also detected during SHS treatment compared to controls. We conclude that decreased mTOR pathway is associated with lessened fetal and placental size during SHS induced IUGR. This decrease was associated with increased caspase 3 and that elevated XIAP protein may signify an attempted protective mechanism that counters increased apoptosis observed in the SHS-induced IUGR placenta. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications.

Support or Funding Information

This work was supported by funding from the Flight Attendant’s Medical Research Institute (FAMRI, PRR and JAA) and by a BYU Mentoring Environment Grant (JAA and PRR).

lt;pgt;This work was supported by funding from the Flight Attendantamp;rsquo;s Medical Research Institute (FAMRI, PRR and JAA) and by a BYU Mentoring Environment Grant (JAA and PRR).lt;/pgt;