DECREASED EXPRESSION OF COLD-INDUCIBLE RNA-BINDING PROTEIN (CIRP) IN MALE GERM-CELLS AT ELEVATED-TEMPERATURE

Physiological scrotal hypothermia is necessary for normal spermatogene sis and fertility in mammals, Cirp is a recently identified cold-induc ible RNA-binding protein that is inducible at 32 degrees C in mouse so matic cells in vitro. Cirp is constitutively expressed in the testis o f mouse and structurally highly similar to RBM1, a candidate for the h uman azoospermia factor, To elucidate the role played by Cirp in sperm atogenesis, we investigated its expression levels during spermatogenes is and after heat stress, In the mouse testis, cirp mRNA was detected in tile germ cells, and the level varied depending on the stage of dif ferentiation. Also, a high level of Cirp protein was detected immunohi stochemically in the nucleus of primary spermatocytes, Expression of C irp was decreased in the GC-2spd(ts) mouse germ cell line when culture temperature was raised from 32 degrees C to 37 degrees C. When mouse testis was exposed to heat stress by experimental cryptorchidism or im mersion of the lower abdomen in warm (42 degrees C) water, the express ion of Cirp was decreased in the testis within 6 hours after either tr eatment. In human testis with varicocele analyzed immunohistochemicall y, germ cells expressed less Cirp protein than those in the testis wit hout varicocele, These results demonstrated that CIRP expression is do wn-regulated at elevated temperature in male germ cells of mice and hu mans. Analysis of Cirp expression in the testes will help elucidate th e molecular mechanisms leading to male infertility.