Editors' ChoiceMALE INFERTILITY

Cilial agitation prevents sperm agglutination

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Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaaw5323
DOI: 10.1126/scitranslmed.aaw5323

Abstract

Agitating cilia produce fluid turbulence to prevent sperm from clogging testicular tubules.

Male and female factors account for similar proportions of infertility cases, yet the cause of male infertility in many cases is unknown. One potential cause of infertility was thought to be a failure of cilia to propel spermatozoa from the testis through the efferent ductules (ED) and into the epididymis, where they mature into fertilizing sperm. A study by Yuan et al. has now disrupted the previously unproven belief that the role of cilia in the ED is to directly propel sperm along these tubules.

The authors used a variety of mouse models to characterize the interaction between ED cilia and spermatozoa. They primarily focused on two miRNA clusters, miR-34b/c and miR-449, which the authors have previously shown to cause loss of functional cilia when knocked out in mice, resulting in male infertility. In knockout mice, the authors identified agglutinated sperm plugs that led to ED obstruction and back pressure in the testis, resulting in failed spermatogenesis. They recapitulated the contribution of back pressure to spermatogenic disruption by ligating the ED tubules and also rescued normal spermatogenesis in knockout mice by relieving the pressure caused by agglutinated sperm.

Next, they investigated why cilial dysmotility resulted in spermatozoal agglutination. As fluid reabsorption by nonciliated cells in the narrow ED tubules increases spermatozoal concentration 25-fold, keeping spermatozoa moving to prevent them from clumping together is especially important. The authors performed imaging in isolated ciliated cells, intact ED, and smooth muscle cells to capture beat patterns and fluid dynamics in real time. Unexpectedly, instead of displaying coordinated movement, the cilia beat asynchronously in different directions and at different frequencies (2 to 8 Hz). The authors showed that this action largely serves to keep spermatozoa in suspension and therefore prevent spermatozoa from agglutinating. Further, they revealed that coordinated contraction of the smooth muscle cells of the ED—not the cilia themselves—pushed the spermatozoa along the tubule to the epididymis.

This study uncovered striking differences in cilial movement and function in the male reproductive tract compared with the female reproductive tract or the lung, where egg cells or inhaled particles are swept along by coordinated cilial movement. These findings may change the way the field approaches cases of infertility in those with cilial motility problems and suggest that certain cases of male infertility could be treated by relieving testicular back pressure.

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