PLACENTAL AUTOPHAGIC AND EPIGENETIC MODIFICATIONS ASSOCIATED WITH FETAL GROWTH RESTRICTION.

MARINO, ANACLARA; MARVALDI, CAROLINA; SCHANDER, JULIETA AYLEN; SILBERMAN, MAGALÍ; WOLFSON, MANUEL LUIS; FRANCHI, ANA MARIA; AISEMBERG, JULIETA

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

SAIC

Intrauterine growth restriction (IUGR) is a condition whereby a fetus is unable toachieve its genetically determined potential size. Most of the adaptive responses of theplacenta to support restricted fetal growth are thought to result in changes in epigeneticregulation. Furthermore, IUGR is associated with placental insufficiency, where alteredtrophoblast cells turnover and function contribute to reduced feto-placental growth. Theaim of this work was (1) to explore placental histone methylation and acetylationprofiles in a mice model of dexamethasone-induced IUGR and (2) to compare thedifferences in autophagy and apoptosis between normal and IUGR placentas.Pregnant BALB/c mice received 8 mg/kg (s.c.) of dexamethasone between days 14and 15 of pregnancy. The control group was sham-treated with saline. Prenatalglucocorticoid treatment not only induced IUGR but also decreased placental weight.Placental tissue from pregnant animals was dissected on gestational days 15 to 18 andprocessed for western blot analysis. Term placentas (day 18) from IUGR fetusesshowed increased levels of Histone 3 acetylation at Lys 9 (H3K9) (p˂0,05). We did notobserve significant changes on the other epigenetic marks like H4K16 acetylation,dimethylation of H3K27 and trimethylation of H3K9, nor were histone deacetylaseSIRT1 levels altered. Mice with IUGR presented higher placental levels of LC3B-II(p˂0,05) on day 18 and lower Bcl2 protein levels (p˂0,05) on day 15 compared withcontrols. There were no significant changes in mTOR and Bax protein levels betweengroups. In summary, dexamethasone-induced IUGR is associated with placentalchanges in epigenetic marks, particularly we found an increase in H3K9 acetylation. Inaddition, dexamethasone treatment led to a decrease in the anti-apoptotic protein Bcl2in placentas on day 15 of pregnancy. Furthermore, signs of augmented autophagywere found in placentas at term.