Zinc Transport Differs in Rat Spermatogenic Cell Types and Is Affected by Treatment with Cyclophosphamide.
Adequate zinc levels are required for proper cellular functions and for male germ cell development. Zinc transport is accomplished by two families of zinc transporters, the ZIPs and the ZnTs, that increase and decrease cytosolic zinc levels, respectively. However, very little is known about zinc transport in the testis. Furthermore, whether cytotoxic agents such as cyclophosphamide (CPA), a known male germ cell toxicant, can affect zinc transport and homeostasis is unknown. We examined zinc transporter expression and zinc transport in pachytene spermatocytes (PS) and round spermatids (RS) in a normal state and after exposure to CPA. We observed differences in the expression of members of the ZnT and ZIP families in purified populations of PS and RS. We also observed that RS accumulate more zinc over time than PS. The expression of many zinc binding genes was altered after CPA treatment. Interestingly, we found that the expression levels of ZIP5 and ZIP14 were increased in PS from animals treated daily with 6 mg/kg CPA for 4 wk but not in RS. This up-regulation led to an increase in zinc uptake in PS but not in RS from treated animals compared to controls. These data suggest that CPA treatment may alter zinc homeostasis in male germ cells leading to an increased need for zinc. Altered zinc homeostasis may disrupt proper germ cell development and contribute to infertility and effects on progeny.
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Anne Marie
AM
Downey
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
Barbara F
BF
Hales
Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada Department of Obstetrics and Gynecology, McGill University, Montréal, Québec, Canada.
Bernard
B
Robaire
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013087:Spermatids / Q000187:drug effects / Q000378:metabolism*; D013090:Spermatocytes / Q000187:drug effects / Q000378:metabolism*; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D009153:Mutagens; C017800:zinc-binding protein; D003520:Cyclophosphamide; D015032:Zinc
chemotherapy; gene expression; immunosuppressant; male germ cells; pachytene spermatocytes; round spermatids; spermatogenesis; testis; toxicology; zinc; zinc transport