Seminal Plasma Factors

Semen, in contrast to other human bodily fluids, contains multiple types of amyloid fibrils under non-diseased conditions. We have demonstrated that these fibrils potently enhance infection by HIV and other sexually transmitted viruses, and characterized the mechanisms by which they do so. We are conducting studies to characterize the physiological function of these fibrils, by assessing how they signal to sperm cells and cells of the female reproductive tract. The effects of seminal plasma components other than semen fibrils are also being characterized both for their effects on HIV infection, reproductive health, as well as to serve as biomarkers of human disease.

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plasma items

The top image shows the ability of semen fibrils (white) to promote HIV infection by facilitating the binding of HIV (red) to cellular targets (blue). Image generated by W. Mothes, J. Luna, and P. Uchil, and used as cover image by Journal of Virology (Roan et al (2009) J Virol 83:73). The bottom image shows electron micrographs of human sperm cells in the absence (left) or presence (right) of semen fibrils. Semen fibrils, in the extracellular space surrounding the sperm cells, directly interact with the sperm membrane (arrows) and affect their activity.

Human spermatozoa before & after entrapment by semen fibrils

Video of sperm interacting with semen fibrils

Panel A shows human sperm cells were attached onto coverslips and examined for motility by live microscopy. Panel B shows these same four spermatozoa 10 minutes after perfusion with purified semen fibrils. The immobilization of spermatozoa by the fibrils is reversible, and promotes disposal of excess or defective sperm cells by phagocytes infiltrating the female reproductive tract. Video generated in collaboration with Polina Lishko (U.C. Berkeley).

Roan et al, Elife. 2017 Jun 27;6. pii: e24888

 

Fibril-associated spermatozoa internalized by macrophage

Video of fibril-associated sperm engulfed by macrophage

Macrophages labeled with a membrane dye (green) were incubated with sperm cells (red) for 3 h in the presence of semen fibrils and then imaged by confocal microscopy. This video demonstrates how semen fibrils can promote phagocytosis of sperm cells by macrophages. Video generated by Nargis Kohgadai and Mauricio Montano (UCSF and the J. David Gladstone Institutes).

Roan et al, Elife. 2017 Jun 27;6. pii: e24888