Polyamines and regulation of spermatogenesis: selective stimulation of late spermatogonia in transgenic mice overexpressing the human ornithine decarboxylase gene.

Abstract

Polyamines are believed to participate in the induction of cell growth, differentiation, and proliferation, but their role in spermatogenesis has remained obscure. Two transgenic mouse lines (K2 and K15) that overexpress the human ornithine decarboxylase (ODC) gene coding for a rate-controlling enzyme in polyamine biosynthesis and, hence, contain high levels of tissue putrescine have been used to study the stage-specific role of ODC in spermatogenesis. In K2 mice with 30-fold testicular ODC overexpression, [3H]thymidine incorporation at stages I-VI of the cycle of the seminiferous epithelium was significantly above the control level. This may reflect a specific stimulation of DNA synthesis in type A4, intermediate, and type B spermatogonia. The K15 mice that have about 70-fold ODC overexpression showed an elevation of DNA synthesis only at stage V of the cycle, suggesting a specific dependence of type B spermatogonia on putrescine. In K15 mice, [3H]thymidine incorporation of stage VIII tubule segments was decreased, suggesting that excess amounts of putrescine selectively inhibit meiotic DNA synthesis. We propose that putrescine has strictly selective local stimulatory and inhibitory actions during spermatogenic DNA synthesis, and that its excess amounts ultimately may lead to decreased fertility.

Polyamines in spermiogenesis: Not now, darling

“…Targeted ODC expression in keratinocytes leads to skin cancer (20). Of greatest relevance to the paper here under discussion, transgenic mice that overexpress ODC in multiple organs exhibit male infertility and disorganization of testicular architecture (21). In mice with 70-fold excess testicular ODC, microscopic analysis shows a reduced number of meiotic and particularly postmeiotic cells.…”

Spermine Synthesis Is Required for Normal Viability, Growth, and Fertility in the Mouse

“…The striking effect of the availability of spermine on the testis, which is likely to account for the infertility of the Gy mice, provides evidence that this polyamine may be needed in some specialized cell types. In this context it is noteworthy that: (a) transgenic mice overexpressing ornithine decarboxylase show an age-related decrease in testicular function (39) and that (b) testicular germ cells express antizyme-3, a novel form of antizyme that regulates polyamine synthesis in a stage-related manner (40).…”

Activation of Polyamine Catabolism Profoundly Alters Tissue Polyamine Pools and Affects Hair Growth and Female Fertility in Transgenic Mice Overexpressing Spermidine/SpermineN 1-Acetyltransferase

“…Even though the exact mechanism(s) leading to ovarian hypofunction and infertility of the female members of the present transgenic animals overexpressing SSAT is not known, it is of interest to note that a testicular overexpression of ODC in transgenic mice caused disturbances of spermatogenesis (13) ultimately leading to male infertility (14). Thus, as in the skin, increases in putrescine could play a role in mediating the effects on ovarian function.…”