Acquisition of volume regulatory response of sperm upon maturation in the epididymis and the role of the cytoplasmic droplet

In certain cases of infertility in domestic species, and in the homozygous c-ros tyrosine kinase knockout mouse, males are infertile as a result of unopposed sperm swelling. This induces flagellar angulation, preventing their normal migration in the female tract. Angulation always occurs at the site of the cytoplasmic droplet located in mature sperm at the annulus (midpiece - principal piece junction). This article reviews the literature on the fate of the sperm's cytoplasmic droplet and suggests a role for it in volume regulation. A hypothesis is presented that during epididymal transit sperm acquire osmolytes accumulated by the epididymal epithelium. This is possibly driven by a mechanism of regulatory volume increase invoked by the hypertonicity of epididymal luminal fluid. These osmolytes are subsequently used for regulatory volume decrease after ejaculation into the relatively hypotonic female tract. Study of the mechanisms of sperm volume regulation may highlight new contraceptive leads.