Figure 3. Pregnant mice exhibit increased body weight loss and mortality and fetal growth restriction.

Non-pregnant (NP) and pregnant (P) (E14.5) mice were exposed to air or to Br2 at 600 ppm for 30 min and returned to room air; they received tadalafil (TAD; 2 mg/kg BW in 0.1 ml of sterile saline) or vehicle via oral gavage at 1 h post-exposure and every 24 h thereafter. Body weights and survival times were recorded daily. A) Kaplan-Meyer curves of pregnant and non-pregnant mice with tadalafil or vehicle, post Br2 exposure. Non-pregnant mice exposed to Br2 and returned to room air lived longer than similarly exposed pregnant mice (* = P<0.05). Tadalafil improved survival times of pregnant mice post Br2 (# = P<0.05) but not of non-pregnant mice; n=10–19; Log-Rank Test. B) Body weights normalized to weights of air-exposed mice. Pregnant mice exposed to Br2 and returned to room air exhibit more severe weight loss compared to similarly exposed non-pregnant mice (* = P<0.05). Tadalafil administration mitigated weight loss in pregnant mice at four days post-exposure, but has no effect in non-pregnant mice; n=6–8; ANOVA. C) Representative ultrasound of a fetus showing how fetal length was measured. D) Summary data of fetal length measurements at E14.5, E16.5, & E18.5. Exposure to Br2 resulted in decreased fetal lengths which were restored to their air control values at E18.5 in the tadalafil group; n= 6–10 pups (2 pups per litter) for each condition; ANOVA; p values as compared to the corresponding air controls for the indicated gestational age. E) Representative photograph of paraformaldehyde-fixed fetuses at E18.5 for the indicated conditions. Fetuses of Br2-exposed pregnant mice exhibit severe fetal growth restriction, and tadalafil improves fetal growth. F) Fetal weights were recorded after extraction of fetuses at E18.5. Fetal weights of fetuses from Br2-exposed pregnant mice weighed considerably less and were partially rescued by tadalafil (TAD); n=pups (11–25) (2 pups per litter); ANOVA. All data are means±S.E.M.