Effects of alcohol, lithium, and homocysteine on nonmuscle myosin-II in the mouse placenta and human trophoblasts.
OBJECTIVE
Mouse embryonic exposure to alcohol, lithium, and homocysteine results in intrauterine growth restriction (IUGR) and cardiac defects. Our present study focused on the placental effects. We analyzed the hypothesis that expression of nonmuscle myosin (NMM)-II isoforms involved in cell motility, mechanosensing, and extracellular matrix assembly are altered by the 3 factors in human trophoblast (HTR8/SVneo) cells in vitro and in the mouse placenta in vivo.


METHODS
After exposure during gastrulation to alcohol, homocysteine, or lithium, ultrasonography defined embryos exhibiting abnormal placental blood flow.


RESULTS
NMM-IIA/NMM-IIB are differentially expressed in trophoblasts and in mouse placental vascular endothelial cells under pathological conditions. Misexpression of NMM-IIA/NMM-IIB in the affected placentas continued stably to midgestation but can be prevented by folate and myoinositol supplementation.


CONCLUSIONS
It is concluded that folate and myoinositol initiated early in mouse pregnancy can restore NMM-II expression, permit normal placentation/embryogenesis, and prevent IUGR induced by alcohol, lithium, and homocysteine.
Department of Pediatrics, University of South Florida/All Children's Hospital Children's Research Institute, St. Petersburg, FL, USA.
Mingda
M
Han
Ana Luisa
AL
Neves
Maria
M
Serrano
Pilar
P
Brinez
James C
JC
Huhta
Ganesh
G
Acharya
Kersti K
KK
Linask
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002492:Central Nervous System Depressants / Q000009:adverse effects; D042783:Endothelial Cells / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D006710:Homocysteine / Q000009:adverse effects; D006801:Humans; D007294:Inositol / Q000494:pharmacology; D018020:Lithium Compounds / Q000009:adverse effects; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D021041:Placental Circulation; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*; D018608:Ultrasonography, Doppler; D014470:Umbilical Cord / Q000098:blood supply / Q000000981:diagnostic imaging; D014803:Vitamin B Complex / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018020:Lithium Compounds; D006710:Homocysteine; D014803:Vitamin B Complex; D000431:Ethanol; D007294:Inositol; D005492:Folic Acid; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB