Abstract
Polyamines are known to play important roles in the proliferation and differentiation of many types of cells. Although considerable amounts of polyamines are synthesized and stored in the testes, their roles remain unknown. Ornithine decarboxylase antizymes (OAZs) control the intracellular concentration of polyamines in a feedback manner. OAZ1 and OAZ2 are expressed ubiquitously, whereas OAZ-t/OAZ3 is expressed specifically in germline cells during spermiogenesis. OAZ-t reportedly binds to ornithine decarboxylase (ODC) and inactivates ODC activity. In a prior study, polyamines were capable of inducing a frameshift at the frameshift sequence of OAZ-t mRNA, resulting in the translation of OAZ-t. To investigate the physiological role of OAZ-t, we generated OAZ-t–disrupted mutant mice. Homozygous OAZ-t mutant males were infertile, although the polyamine concentrations of epididymides and testes were normal in these mice, and females were fertile. Sperm were successfully recovered from the epididymides of the mutant mice, but the heads and tails of the sperm cells were easily separated in culture medium during incubation. Results indicated that OAZ-t is essential for the formation of a rigid junction between the head and tail during spermatogenesis. The detached tails and heads were alive, and most of the headless tails showed straight forward movement. Although the tailless sperm failed to acrosome-react, the heads were capable of fertilizing eggs via intracytoplasmic sperm injection. OAZ-t likely plays a key role in haploid germ cell differentiation via the local concentration of polyamines.
Highlights
As many as 15% of human couples [1] are infertile, and male infertility is associated with about half of these cases
Ornithine decarboxylase antizymes (OAZs) protein is translated by programmed +1 frameshifting to inhibit ornithine decarboxylase (ODC) activity and the OAZ–ODC complex drives the rapid degradation of ODC by the 26S proteasome [10,11,12,13,14,15]
Ornithine decarboxylase antizymes (OAZs) are enzymes that control the concentration of polyamines in cells
Summary
As many as 15% of human couples [1] are infertile, and male infertility is associated with about half of these cases. One of them (TISP15) encoded the Ornithine decarboxylase antizyme (OAZ) known to control the intracellular concentration of polyamines [3,4]. Full-length TISP15, known as OAZ in testis (OAZ-t/OAZ3), was expressed in haploid germ cells [4,5]. Polyamines, such as putrescine, spermidine, and spermine, are essential for cell proliferation and differentiation via binding to nucleic acids as cations [6,7]. The RNA expression of somatic OAZ1 was decreased during the later stages of haploid germ cell differentiation [4]. Further analysis of OAZ-t revealed that polyamines are capable of inducing a frameshift at the frameshift sequence in OAZ-t mRNA
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