previously demonstrated, in our mouse model, that pups resulting from embryos transferred into a superovulated environment were significantly smaller than those transferred into a hormonally physiologic milieu. 2 The objective of this study was to study the effect of the peri-implantation environment on vasculogenesis and fetal blood flow in the term placenta in a mouse model. DESIGN: Laboratory research. MATERIALS AND METHODS: Mice were superovulated, mated and 2pronuclear embryos were collected and cultured to the blastocyst stage. Ten blastocysts were transferred into each pseudopregnant female created through either natural mating (NAT) to a vasectomized male or following superovulation (SO) and mating to a vasectomized male. Near term, on day E17.5, the pregnant mice were evaluated with a high frequency linear 40 MHZ ultrasound probe by a single, blinded, experienced sonographer. Assessment of umbilical artery Doppler flow was performed on each pup at the segment of cord insertion to the fetal abdomen and three recordings were made for each vessel. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were measured and resistance index (RI) was calculated as (PSVÀEDV)/PSV. On E18.5, the pregnant mice were sacrificed and the placentas were isolated and fixed for histology. Placental endothelial cells were stained with an antibody to MECA32. Microvascular density in the placenta labyrinth zone was determined using Aperio Image Analysis software. Student's T-test and Mann-Whitney U-tests were used to compare differences between groups. RESULTS: There was no difference in litter size between NAT (n¼15 litters) and SO (n¼13 litters) hosts. As previously demonstrated, pups from the SO recipients were significantly smaller than mice from the NAT recipients. Pups resulting from embryo transfers into the SO environment had significantly higher umbilical artery RI compared to pups resulting from transfer into NAT recipients [0.917 SO (n¼16 from 6 litters) vs. 0.896 NAT (n¼30 from 10 litters), p¼0.02]. Immunohistochemistry demonstrated significantly lower microvascular density in the placentas resulting from the SO recipients compared to the NAT recipients [1.24x10-3 vessels/mm 2 SO (n¼14) vs. 1.46x10-3 vessels/mm 2 NAT (n¼15), p<0.05)]. CONCLUSIONS: In a mouse model of ART, the peri-implantation hormonal milieu following superovulation has a significant effect on umbilical artery resistance and microvascular density in the placenta. Our data strongly suggest that the peri-implantation hormonal milieu following superovulation leads to altered vasculogenesis in the developing placenta, resulting in altered fetal growth and an increase in disorders of placentation. References:
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