Prenatal zinc deficiency: influence on heart morphology and distribution of key heart proteins in a rat model.
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 alpha-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.
Lopez
Veronica
V
Department of Nutrition, University of California, Davis, One Shields Ave., Meyer Hall, Davis, CA 95616, USA.
Keen
Carl L
CL
Lanoue
Louise
L
D000199:Actins / Q000378:metabolism; D000818:Animals; D018959:CD57 Antigens / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D004435:Eating; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D050991:GATA4 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009432:Neural Crest / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000172:deficiency*
D000199:Actins; D018959:CD57 Antigens; D018031:Connexin 43; D050991:GATA4 Transcription Factor; D015032:Zinc; C498862:Acta2 protein, rat