Prenatal stress challenge impairs fetal development in mice via decrease of proliferin expression in trophoblast Giant Cells

MARIA EMILIA SOLANO; CLEMENS STEINERT; EVELIN HAGEN; SANDRA BLOIS; ALICIA BEATRIZ MOTTA; DOUGLAS AJ; PETRA ARCK

Chicago, IL, USA

Congreso; 28th Annual Meeting of Reproductive Immunology, Chicago, IL, June 11 - 14, 2008; 2008

American Society for Reproductive Immunology

Emerging epidemiological evidence indicates that prenatal challenge to stress may affect fetal development in utero. Stress also decreases levels of progesterone (P) in maternal serum. During late gestation in mice, P is largely synthesized by placental trophoblast Giant Cells (GC). Thus, the goal of the present study was to study the effect of stress challenge during late gestation on placental integrity and function as well as fetal development. DBA/2J -mated BALB/c females were exposed to 24 h sound stress on gestation days (gd) 12.5 and 14.5 and injected with the P derivative dydrogesterone (D) or vehicle on gd 11.5, 13.5 and 15.5, non-stressed sham injected pregnant females served as controls. On gd 16.5 fetal development was documented using the Theiler Stage (TS) criteria, fetal weight was determined. We observed growth restricted fetuses in pregnancies challenged by stress (TS 24,48±0,08 n=60 in control vs. 24,26±0,07 n=83 in stress, P<0.05) along with a decreased weight (535±6 vs. 526±7 mg). Tissue sections from placental tissue specimen were stained for Periodic Acid Schiff Reaction and Hematoxilin & Eosin (H&E) and Placental proliferin (Plf) expression was analyzed by immunohystochemistry. Placental integrity such as morphology of spongiotrophoblast and labyrinth layers was not altered by stress, whereas placental function, as evaluated by Plf intensity in GC, was reduced. No increase of GC apoptosis, evaluated by TdT Biotin-dUTP Nick End Labeling (TUNEL), could be detected. Supplementation of D abrogated partially the stress-induced intrauterine growth restriction (IUGR): TS 24,39±0,07; weight 536±8 mg, n=82. Therefore we conclude that the loss of GC endocrine function, such as production of the angiogenic factor Plf, plays a key role in stress-induced IUGR.