A mouse model of familial oligoasthenoteratozoospermia.

BACKGROUND Hrb is an HIV-1 Rev-binding/interacting protein and is a cofactor for Rev export pathway. Hrb interacts with Eps15 homology (EH) domain-containing proteins and is a component of EH network and functions in vesicle sorting. Earlier, we reported that Hrb-deficient male mice are infertile and that they show oligozoospermia. Their sperm lack acrosomes and present globozoospermia. The aim of this study was: (i) to investigate the additional defects in spermatogenesis in Hrb-deficient mice; and (ii) to investigate the effect of acrosomelessness on spermatid differentiation in Hrb-deficient mice. METHODS Hrb(-/-) testes, epididymides, spermatids and sperm were analyzed by histology and electron microscopy. Centrioles were analyzed in spermatids and sperm by indirect immunofluorescence technique. RESULTS Hrb(-/-) male mice exhibited multiple anomalies during meiosis and spermiogenesis that produced developmentally impaired sperm with unshaped or deformed nuclei, loss in cell polarity, intracellular flagellar coiling, multinucleation, supernumerary centrioles and multiflagellation. A total of 13.0% Hrb(-/-) sperm showed macrocephaly. The Hrb(-/-) sperm exhibited variation in head size and shape, disarranged cellular organelles, nuclear and cytoplasmic vacuolization, mitochondrial loss or scattering and no forward motility. CONCLUSIONS These aberrations, in Hrb(-/-) mouse spermatids and sperm, are reminiscent of human familial male infertility with oligoasthenoteratozoospermia syndrome. The Hrb-deficient mouse may be useful in understanding familial oligoasthenoteratozoospermia syndrome.