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βENaC is Required for Placental Vascular Remodeling in Mice
Author(s) -
Warrington Junie Paula,
Spradley Frank T,
Chade Alejandro R,
Ryan Michael J,
Granger Joey P,
Drummond Heather A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1034.1
Subject(s) - spiral artery , intervillous space , trophoblast , placenta , endocrinology , medicine , fetus , biology , anatomy , andrology , pregnancy , genetics
During normal pregnancy, spiral arteries of the maternal uterus remodel into large, low‐resistance vessels to accommodate increasing blood flow to the developing utero‐placental unit. During spiral artery remodeling, endothelial and vascular smooth muscle cells (VSMCs) are replaced by fetal‐derived cytotrophoblasts. We and others have shown that beta Epithelial Na + Channel protein (βENaC) is required for normal trophoblast migration in vitro. However, whether βENaC mechanistically contributes to trophoblast migration underlying placental vascular remodeling is unknown. In this study, we tested the hypothesis that bENaC is required for normal placental vascular remodeling. To address this, we examined placental vascular morphology and trophoblast/VSMC localization in mice with reduced βENaC expression (βENaC m/m ). Mutant and wild‐type (βENaC +/+ ) controls were mated to generate age‐matched, timed‐pregnant mice. Micro‐computed tomography analysis of gestational day 14.5 placental vascular casts (n = 7–8 placentas) showed reduced spiral artery density (0.4 ± 0.1 vs. 0.7 ± 0.1 per mm 2 ) and mean diameters (185.1 ± 6.9 μm vs. 225.0 ± 8.3 μm; p<0.01) in βENaC m/m mice compared to wild‐type mice respectively. Additionally, the central canal vessel diameter was also reduced in βENaC m/m mice (318.6 ± 11.8 vs. 373.0 ± 19.6 μm). There was no difference in the intervillous space. On gestational day 18.5, another group of placentas were collected for immunofluorescent detection of trophoblast (cytokeratin‐13, CK‐13) and smooth muscle cell (desmin) presence in spiral arteries. In βENaC +/+ mice, we detected cytotrophoblast, but not VSMC marker expression. However, CK‐13 expression was reduced and desmin increased in βENaC m/m placentas. Although pup (0.82 ± 0.04 vs. 0.85 ± 0.06 g) and placenta weights (110 ± 5 vs. 110 ± 3 mg) were similar in mutant and wild‐type mice, respectively, βENaC m/m mice had fewer live pups (5 ± 1 vs. 9 ± 1, p=0.002) on gestational day 18.5. Taken together, these findings suggest that βENaC is required for normal utero‐placental vascular remodeling during pregnancy and mice with reduced βENaC may compensate by having smaller litter size. Support or Funding Information Funding: NIH grants P20GM104357, P01HL051971, K99HL129192, and the American Heart Association grant: 13POST16240000.