CONICET | Buscador de Institutos y Recursos Humanos

Intrauterine growth restriction (IUGR) is a conditionwhereby a fetus is unable to achieve its genetically determined potential size.Most of the adaptive responses of the placenta to support restricted fetalgrowth are thought to result in changes in epigenetic regulation. Furthermore, IUGRis associated with placental insufficiency, where altered trophoblast cellsturnover and function contribute to reduced feto-placental growth. The aim ofthis work was (1) to explore placental histone methylation and acetylation profilesin a mice model of dexamethasone-induced IUGR and (2) to compare the differencesin autophagy and apoptosis between normal and IUGR placentas. Pregnant BALB/c micereceived 8 mg/kg (s.c.) of dexamethasone between days 14 and 15 of pregnancy. Thecontrol group was sham-treated with saline. Prenatal glucocorticoid treatmentnot only induced IUGR but also decreased placental weight. Placental tissuefrom pregnant animals was dissected on gestational days 15 to 18 and processedfor western blot analysis. Term placentas (day 18) from IUGR fetuses showedincreased levels of Histone 3acetylation at Lys9 (H3K9) (p˂0,05). We did not observe significantchanges on the other epigenetic marks like H4K16 acetylation, dimethylation ofH3K27 and trimethylation of H3K9, nor were histone deacetylase SIRT1 levelsaltered. 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 with controls. There were nosignificant changes in mTOR and Bax protein levels between groups. In summary,dexamethasone-induced IUGR is associated with placental changes in epigeneticmarks, particularly we found an increase in H3K9 acetylation. Inaddition, dexamethasone treatment led to a decrease in the anti-apoptotic proteinBcl2 in placentas on day 15 of pregnancy. Furthermore, signs of augmentedautophagy were found in placentas at term.