Fetal origin of adult disease: insights on mechanistic cues and therapeutic targets arising from a mouse model

MARIA EMILIA SOLANO; CLEMENS STEINERT; BRUENAHL C; EVELIN HAGEN; SANDRA BLOIS; MOTTA, AB; DOUGLAS AJ; PETRA ARCK

Orlando, USA

Congreso; 29 Reunión Anual de la American Society for Reproductive Immunology (ASRI).; 2009

Sociedad Americana de Inmunologia Reproductiva

Prenatal stress challenge is a pivotal environmental factor which increases the vulnerability of the offspring to develop chronic diseases in later life. Insights on mechanistic cues involved in such heightened vulnerability still remain largely elusive. Thus, the aim of our study was to identify maternal mediators and mechanisms through which prenatal stress affects intrauterine fetal development. DBA/2J -mated BALB/c females were exposed to 24 hr sound stress on gestation days (gd) 12.5 and 14.5. Non-stressed females served as controls. Food intake and maternal weight were documented. On gd 15.5, 15.75 and 16.5 animals were sacrificed, blood samples, placentas, fetuses and amniotic fluids collected. Progesterone and testosterone, determined in maternal serum by radioimmunoassay, were reduced by stress challenge, along with placental endocrine dysfunction, evaluated by low proliferin (Plf) expression in giant cells (GC) analyzed by immunohystochemistry. However, the placental morphology was not altered by stress and no increase of GC apoptosis could be detected, as evaluated by TdT biotin-dUTP nick end labeling (TUNEL). We further observed an inverse association between food intake and maternal and fetal weight. Fetal development, evaluated using the Theiler stage (TS) criteria, was impaired upon prenatal stress challenge, leading to growth restricted fetuses especially in female fetuses.