Organic and inorganic zinc show similar regulatory effects on the expression of some germ cell specific markers induced in bone marrow mesenchymal stem cells after treatment with retinoic acid
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Chemical approaches and small molecules are considered as an inseparable part of regenerative medicine and stem-cell-based therapies. Zinc (Zn) is a well-known trace element essential for normal spermatogenesis and has a regulatory role on the expression of several genes in different tissues of the body. This study determines and compares the effects of organic (acetate, ZnA) and inorganic Zinc (sulfate, ZnS) on the expression of a number of germ cell (GC)-specific genes in retinoic acid (RA)-treated ram bone marrow mesenchymal stem cells (BM-MSCs). First, BM-MSCs were treated with 10 μM RA for 21 days, real-time RT-PCR and immunocytochemistry (ICC) confirmed the expression of the markers in treated cells. Then, in vitro-derived GCs were treated with 1 μM of either ZnS or ZnA for one week. Treatment of in vitro-derived GCs with ZnA significantly downregulated all tested genes. ZnS treatment also induced a significant downregulation in Piwil2 and Vasa, and a moderate decrease in ITG b1 and Oct4 expression levels. Cells treated with ZnS or ZnA showed almost similar gene expression patterns. Zn treatments appeared to make in vitro-derived GCs return to a state similar to the untreated MSCs. We also studied the effects of simultaneous use of RA and one of zinc ions on BM-MSCs. The results showed that presence of organic or inorganic zinc in culture medium containing RA inhibited BM-MSCs to differentiate into GCs. This study showed a new dimension of zinc effect on stem cells which will be really helpful for establishment of novel strategies for Zn applications.
KeywordsMesenchymal stem cells Germ cell markers In vitro-derived germ cells Retinoic acid Zinc acetate Zinc sulfate
Bone marrow mesenchymal stem cells
Mesenchymal stem cells
Reverse transcription polymerase chain reaction
This study was supported financially by research grants from Royan Institute (grant No: 160) and Damghan University in collaboration with Babol University of Medical Sciences.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
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