ABSTRACT
Pregnant rats were subjected to either a folic-acid-deficient regimen that produces multiple congenital skeletal malformations, or a control folic-acid-supplemented regimen. Fetal limbs were extirpated on days 16 and 18 of gestation, pooled from each litter, homogenized, and aliquots set aside for hydroxyproline, protein and DNA determinations. We found that (1) the amount of protein recovered per treated limb was approximately half that of controls on both days, (2) the amount of protein recovered per treated or control day-18 limb was twice that of a day-16 limb, (3) treated limbs constituted the same percentage of total body weight as in controls on day 16, but a smaller percentage than in controls on day 18, and (4) the concentration of hydroxyproline (μg/mg protein) was significantly less for treated limbs than for controls on day 18 of gestation. We noted also that: (1) lowest hydroxyproline concentrations were found in limbs from treated fetuses with gross limb malformations, (2) intermediate concentrations were found in limbs of treated fetuses not exhibiting gross limb malformations, and (3) highest concentrations were found in control limbs. We suggest that the treatment resulted in (1) a decreased rate of accumulation of protein in limbs prior to day 16, but not from day 16 to day 18, (2) a decreased rate of accumulation of some non-protein component(s) in treated limbs from day 16 to day 18, and (3) an altered collagen metabolism.
We wish to thank Dr E. W. Cantrall, Director, Preclinical Development, Lederle Laboratories, Pearl River, New York, for his generous donation of 9-methyl pteroylglutamic acid.
