Expression of aquaporins in the efferent ductules, sperm counts, and sperm motility in estrogen receptor-α deficient mice fed lab chow versus casein

Estrogens play an important role in the male reproductive tract, and this is especially so for the efferent ductules, where of alpha-estrogen receptors (ER alpha) have been localized. Mice deficient in ER alpha (alpha ERKO mice) are infertile, and the effect appears to be due in part to retention of water at the level of the efferent ductules. In the present study, we examined the consequences of ERa deletion on the distribution of certain aquaporins (AQPs), water protein channels, in the efferent ductules and on sperm numbers and motility. In addition, the effects of feeding mice a regular lab chow diet, which contains phytoestrogens, known to affect male reproductive tract functions, and a casein diet, which lacks phytoestrogens, were also assessed. Light microscope immunolocalizations of AQP-1 and AQP-9 revealed dramatic reduction and patchier staining in aERKO mice with distal areas of the efferent ductules being more affected than proximal areas. No other changes in immunolocalizations were noted as a consequence of diet. Computer-assisted sperm analyses demonstrated a 62% reduction in cauda epididymal sperm/ml in aERKO mice fed lab chow, whereas 87% fewer sperm/ml were observed in aERKO mice fed casein, suggesting an enhanced role for sperm production and concentration in a diet containing phytoestrogens. All sperm motility parameters were altered to some degree in aERKO mice fed lab chow, Alterations in sperm motility parameters were also detected, but were less dramatic in aERKO mice fed casein. These data suggest that the decrease in AQP expression in the efferent ductules of alpha ERKO mice contributes in part to water retention in this tissue, eventually leading to backflow of water into the testis, with subsequent decreases in sperm concentration and motility. The data also suggest that phytoestrogens, which are present in regular lab chow, can influence the male reproductive tract with and without the presence of ERa, promoting efferent ductule and epididymal functions when ER alpha is expressed, but inhibiting these same functions when ER(x is missing. Taken together the data underscore the importance of estrogens and ER alpha in maintaining sperm maturation and preventing male infertility.