Prenatal zinc deficiency: Influence on heart morphology and distribution of key heart proteins in a rat model

Veronica Lopez, Carl L Keen, Louise Lanoue

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The etiology of congenital heart disease is multifactorial, with genetics and nutritional deficiencies recognized as causative agents. Maternal zinc (Zn) deficiency is associated with an increased risk for fetal heart malformations; however, the contributing mechanisms have yet to be identified. In this study, we fed pregnant rats a Zn-adequate diet (ZnA), a Zn-deficient (ZnD), or a restricted amount of Zn adequate diet (RF) beginning on gestation day (GD) 4.5, to examine whether increased cell death and changes in cardiac neural crest cells (NCC) play a role in Zn deficiency-induced heart defects. Fetuses were collected on GD 13.5, 15.5, and 18.5 and processed for GATA-4, FOG-2, connexin-43 (Cx43), HNK-1, smooth muscle α-actin (SMA) and cleaved caspase-3 protein expression. Fetuses from ZnA-fed dams showed normal heart development, whereas fetuses from dams fed with the ZnD diet exhibited a variety of heart anomalies, particularly in the region of the outflow tract. HNK-1 expression was lower than normal in the hearts of GD13.5 and 15.5 ZnD fetuses, particularly in the right atrium and in the distal tip of the interventricular septum. Conversely, Cx43 immunoreactivity was increased throughout the heart in fetuses from ZnD dams compared to fetuses from control dams. The distribution and intensity of expression of SMA, GATA-4, FOG-2, and markers of apoptosis were similar among the three groups. We propose that Zn deficiency induced alterations in the distribution of Cx43 and HNK-1 in fetal hearts contribute to the occurrence of the developmental heart anomalies.

Original languageEnglish (US)
Pages (from-to)238-255
Number of pages18
JournalBiological Trace Element Research
Volume122
Issue number3
DOIs
StatePublished - Jun 2008

Fingerprint

Zinc
Rats
Fetus
Connexin 43
Nutrition
Diet
Fetal Heart
Dams
Proteins
Smooth Muscle
Actins
Pregnancy
Muscle
Neural Crest
Heart Atria
Malnutrition
Caspase 3
Heart Diseases
Cell Death
Mothers

Keywords

  • Cardiac neural crest cells
  • Cell death
  • Connexin 43
  • Heart development
  • HNK-1
  • Nutrition
  • Rat
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Inorganic Chemistry
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Biochemistry, Genetics and Molecular Biology(all)
  • Endocrinology

Cite this

Prenatal zinc deficiency : Influence on heart morphology and distribution of key heart proteins in a rat model. / Lopez, Veronica; Keen, Carl L; Lanoue, Louise.

In: Biological Trace Element Research, Vol. 122, No. 3, 06.2008, p. 238-255.

Research output: Contribution to journalArticle

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