Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.
BACKGROUND
We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology.


METHODS
Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60.


RESULTS
Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups.


CONCLUSIONS
These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.
Summers
Brooke L
BL
Hanson Institute/Institute of Medical and Veterinary Science, Adelaide, SA, Australia.
Rofe
Allan M
AM
Coyle
Peter
P
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000437:Alcoholism / Q000150:complications; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000517:prevention & control*; D012965:Sodium Chloride / Q000494:pharmacology; D015032:Zinc / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D000431:Ethanol; D012965:Sodium Chloride; D008668:Metallothionein; D015032:Zinc