TY - JOUR
T1 - The effect of zinc on human trophoblast proliferation and oxidative stress
AU - Jankovic-Karasoulos, Tanja
AU - McAninch, Dale
AU - Dixon, Clare
AU - Leemaqz, Shalem Y.L.
AU - François, Maxime
AU - Leifert, Wayne R.
AU - McCullough, Dylan
AU - Ricciardelli, Carmela
AU - Roberts, Claire T.
AU - Bianco-Miotto, Tina
N1 - Funding Information:
The research was funded by the National Health and Medical Research Council (NHMRC) Project Grant ( GNT1161079 ) awarded to CTR who is also supported by a NHMRC Investigator Grant ( GNT1174971 ).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/4
Y1 - 2021/4
N2 - Adequate Zinc (Zn) intake is required to prevent multiple teratogenic effects however deviations from adequate Zn intake, including high maternal Zn status, have been linked to increased incidence of pregnancy complications, including those associated with inadequate placentation. Using placental trophoblast HTR8/SVneo cells and first trimester human placental explants (n = 12), we assessed the effects of varying Zn concentrations on trophoblast proliferation, viability, apoptosis and oxidative stress. Compared to physiologically normal Zn levels (20 µM), HTR-8/SVneo cell proliferation index was significantly lower in the presence of physiologically elevated (40 µM; P = .020) and supra-physiological (80 µM; P = .007) Zn. The latter was also associated with reduced proliferation (P = .004) and viability (P < .0001) in cultured placental explants, but not apoptosis. Reactive oxygen species production in HTR8/SVneo cultures was significantly higher in the presence of 80 µM Zn compared to all physiologically relevant levels. Oxidative stress, induced by an oxidizing agent menadione, was further exacerbated by high (80 µM) Zn. Zn did not affect lipid peroxidation in either HTR8/SVneo cells or placental explants or antioxidant defense mechanisms that included glutathione reductase and superoxide dismutase. Further study should focus on elucidating mechanisms behind impaired trophoblast proliferation and increased oxidative stress as a result of elevated Zn levels.
AB - Adequate Zinc (Zn) intake is required to prevent multiple teratogenic effects however deviations from adequate Zn intake, including high maternal Zn status, have been linked to increased incidence of pregnancy complications, including those associated with inadequate placentation. Using placental trophoblast HTR8/SVneo cells and first trimester human placental explants (n = 12), we assessed the effects of varying Zn concentrations on trophoblast proliferation, viability, apoptosis and oxidative stress. Compared to physiologically normal Zn levels (20 µM), HTR-8/SVneo cell proliferation index was significantly lower in the presence of physiologically elevated (40 µM; P = .020) and supra-physiological (80 µM; P = .007) Zn. The latter was also associated with reduced proliferation (P = .004) and viability (P < .0001) in cultured placental explants, but not apoptosis. Reactive oxygen species production in HTR8/SVneo cultures was significantly higher in the presence of 80 µM Zn compared to all physiologically relevant levels. Oxidative stress, induced by an oxidizing agent menadione, was further exacerbated by high (80 µM) Zn. Zn did not affect lipid peroxidation in either HTR8/SVneo cells or placental explants or antioxidant defense mechanisms that included glutathione reductase and superoxide dismutase. Further study should focus on elucidating mechanisms behind impaired trophoblast proliferation and increased oxidative stress as a result of elevated Zn levels.
KW - Zinc
KW - oxidative stress
KW - placenta
KW - proliferation
KW - trophoblasts
UR - http://www.scopus.com/inward/record.url?scp=85099628632&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2020.108574
DO - 10.1016/j.jnutbio.2020.108574
M3 - Article
C2 - 33388345
AN - SCOPUS:85099628632
SN - 0955-2863
VL - 90
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
M1 - 108574
ER -