Reversibility of Developmental Retardation following Murine Fetal Zinc Deprivation

Abstract

To investigate the effects and reversibility of moderate prenatal zinc deprivation, pregnant mice were fed, beginning on day 7 of gestation, a diet containing either 100 ppm (control) or 5 ppm zinc; pair-fed controls were also studied. Nutritional manipulation was limited to the prenatal period. Zinc-deprived dams had significantly smaller litters than did controls, and postnatal survival was markedly compromised. Progeny of zinc-deprived dams displayed significant growth retardation, as reflected by lower body weight and length than controls, whether ad libitum-fed or pair-fed. Growth of spleen and thymus was affected by zinc deprivation to a significantly greater extent than was growth of heart, kidney or brain. Cross-fostering of control pups to zinc-deprived dams resulted in delayed growth; however, retardation was not as great as that observed in deprived pups allowed to suckle their natural mothers. Cross-fostering of zinc-deprived pups to control dams improved growth of most organs, but did little to improve growth of spleen and, most notably, thymus. Zinc-deprived pups exhibited considerable "catch up" growth following neonatal zinc repletion, and by 6-8 weeks of age, no significant differences between control and deprived offspring were observed.

Novel two-dimensional morphometric maps and quantitative analysis reveal marked growth and structural recovery of the rat hippocampal regions from early hypothyroid retardation

“…Attempts to "catch-up" growth of body and brain weight during the postnatal phase have been observed in response to a divergent group of adverse insults during the perinatal period. These include under-and malnutrition, cerebral ischemia, cranial x-irradiation, and exposure to teratogens and drugs (Beach et al, 1982;Clayton et al, 1988;Groziak et al, 1984;Meyer et al, 1990;Slotkin et al, 1986;Weichsel & Clark, 1977;Williams & Hughes, 1978). Once the growth-retarding agent is removed there is resumption of growth rather than a rebound of growth activity.…”

Prenatal Zinc Treatment at the Time of Acute Ethanol Exposure Limits Spatial Memory Impairments in Mouse Offspring

“…In rodents, there are similarities in fetal outcome between prenatal Zn deficiency and prenatal ethanol exposure. These include increased fetal resorptions, low birth weight, and birth abnormalities (7)(8)(9)(10). These effects are potentiated during organogenesis (GD 7-12 in rodents, weeks 3-9 in humans), a period during early pregnancy critical for development and cell differentiation.…”

Zinc Supplementation Selectively Decreases Fetal Hepatocyte DNA Synthesis and Insulin-Like Growth Factor II Gene Expression in Primary Culture

“…It is difficult to compare other in vivo studies using dietary restriction of Zn with these direct, in vitro observations of the effects of provision of adequate Zn to proliferating fetal hepatocytes, In our experiments, provision of Zn in physiologic concentrations augmented DNA synthesis in nonhepatocytes, more in keeping with previous whole-animal studies. Also, careful analysis of studies in mice in which Zn deprivation was begun during pregnancy and continued throughout gestation demonstrated larger liver size in Zndeficient mice after birth than in Zn-sufficient, pair-fed controls (23). Other organs were not similarly affected (23).…”

“…Also, careful analysis of studies in mice in which Zn deprivation was begun during pregnancy and continued throughout gestation demonstrated larger liver size in Zndeficient mice after birth than in Zn-sufficient, pair-fed controls (23). Other organs were not similarly affected (23). It is likely that Zn may have direct effects on control of cellular growth through actions on specific DNA or RNA polymerases and other enzymes (2, 3) as well as indirect effects that may be mediated through regulation of transcription of important growth factors, such as the IGF.…”