title: Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton.
abstract: Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non-calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague-Dawley rats (180-250 g) were fed 1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), 2) a zinc-deficient diet (0 microgram/g) ad libitum (group ZD), or 3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed. Fetuses were weighed, examined for external malformations, and stained in toto with a double-staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety-one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non-calcified bone, were not mentioned in previous reports, thus stressing the importance of using double-staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteration of the Ca:P ratio.
authors.affiliation: Department of Pediatrics, University Clinic of Navarra, University of Navarra, Pamplona, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: da Cunha Ferreira
authors.forename: I M
authors.initials: IM
authors.lastname: Marquiegui
authors.forename: I V
authors.initials: IV
authors.lastname: Elizaga
mesh_terms: D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000002:abnormalities* / Q000378:metabolism; D002114:Calcinosis / Q000209:etiology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000013:Congenital Abnormalities / Q000209:etiology; D005314:Embryonic and Fetal Development; D005260:Female; D010758:Phosphorus / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism
chemical_list: D010758:Phosphorus; D015032:Zinc; D002118:Calcium