Effect of Pyrimethamine on DNA Synthesis of Germ Cells in Mice Testis

Lee, Sang Kon; Lee, Jong Sup; Kim, Kyung Ahn; Cho, Jin Seon

Abstract

Pyrimethamine(PYR) produces reversible infertility in mice. The antifertility effect of PYR is due to its antifolate action. PYR causes male infertility in Balb C mice in a dose dependent manner. The present study was performed to determine DNA synthesis of germ cell in mice treated with PYR. For 6-8 weeks adult Balb C mice were administered a PYR dose of 100mg- 200mg/ kg/day suspended in vegetable oil.10 control mice received only vegetable oil without PYR. After 7 weeks administration 28.6% of mice(4/14) administered a PYR dosage of 100mg/kg were infertility, whereas all of those(4/4), 200mg/kg/day were infertile. Morphologic changes of the testis induced by orally administered PYR were spermatogenic arrest and depopulation of germ cell. The incorporation of thymidine into DNA of germ cells was studied by using autoradiography after intraperitoneal injection of 15 Ci of methyl-3H-thymidine. Synthesis of DNA takes place in interphase and early prophase of mitotic phase of germ cell. The synthesis of DNA in spermatogonia reduced in all stage of spermatogenesis in mice treated with PYR due to spermatogenic arrest, compared with that of control mice. These results suggest that reduced synthesis of DNA in spermatogonia by PYR administration caused hypospermatogenesis. PYR represents further approach toward development of male contraceptive.