Preconception Zinc Deficiency Disrupts Postimplantation Fetal and Placental Development in Mice1

Abstract

Zinc is an essential nutrient for optimal fertility, but the effects of preconception zinc deficiency on postimplantation development are not known. Female mice were fed a control or a zinc-deficient diet (ZDD) for 4-5 days before ovulation (preconception). Embryonic and/or placental development were evaluated on Days 3.5, 6.5, 10.5, 12.5, and 16.5 of pregnancy. The findings show a decrease in embryo length (31%, Day 10.5; 13%, Day 12.5; 10%, Day 16.5) and weight (23%, Day 16.5) in embryos from mothers fed a ZDD preconception. Zinc deficiency also caused a high incidence of pregnancy loss (46%, Day 10.5; 34%, Day 12.5; 51%, Day 16.5) compared to control (2%, Day 10.5; 7%, Day 12.5; 9%, Day 16.5). ZDD embryos transferred to normal recipients were 38% smaller and implantation rate was only 10% compared to 40% for controls. Trophoblast cell differentiation and implantation on Day 6.5 of pregnancy were compromised by preconception zinc deficiency. On Day 12.5 of pregnancy, placenta weight and area of fetal placenta were decreased 37% and 31%, respectively, by preconception zinc deficiency. Consistent with a smaller fetal placenta, expression of key placental transcripts, including Ar, Esx1, Syna, Tfeb, Dlx3, and Gcm1 mRNA, but not Ctsq mRNA, were decreased 30%-70% in the ZDD group. Preconception zinc deficiency caused 41%-57% of embryos to exhibit delayed or aberrant neural tube development, as examined by light microscopy and magnetic resonance imaging. Collectively, the findings provide evidence for the importance of preconception zinc in promoting optimal fertility and oocyte developmental potential.

Association between Maternal Zinc Status, Dietary Zinc Intake and Pregnancy Complications: A Systematic Review

“…There is consistent evidence in animal models that maternal dietary zinc deficiency during pregnancy reduces fetal growth [16,17,18,19]. From the studies that measured maternal zinc intake during pregnancy reviewed here, a possible relationship between low zinc intake (≤54% of the recommended 11 mg/day) and decreased infant birthweight may exist in human populations.…”

“…The importance of zinc to the growth of the fetus is demonstrated by the active transport of zinc across the placenta into the fetal circulation resulting in higher cord blood concentrations compared to those in the maternal circulation [11,12,13,14]. Rodent models of severe maternal zinc deficiency show increased rates of fetal loss and congenital malformations in the surviving fetuses [15] as well as reduced fetal growth [16,17,18], lower implantation rates and impaired placental growth [19], all highlighting the teratogenic effects of zinc deficiency in pregnancy.…”

Micronutrient deficiencies in pregnancy worldwide: health effects and prevention

“…51 Among a variety of roles played by zinc to support pregnancy, 52 zinc deficiency was found to impede placental development, including trophoblast differentiation, placental size, weight, and protein expression in a mouse model of periconceptional zinc deficiency. 53 …”

Maternal control of early embryogenesis in mammals

“…In women, low body weight due to dietary restriction is linked to reduced fertility and results in significant changes in gonadotropin hormones to levels similar to those in women with ovarian insufficiency (Bates 1985). Mice on a zinc-deficient diet produced smaller fetuses and are prone to neural tube defects (Tian et al 2014). In such animals, histone methylation was decreased in oocytes and retained in the maternal pronucleus after fertilization (Tian and Diaz 2013).…”