You are here

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 infection by HIV and other sexually transmitted viruses including Zika virus, on reproductive health, as well as to serve as biomarkers of human disease.

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.

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

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

Funding Sources for Project

NIH R21 AI116252 “Characterization of gallic acid as a novel HIV microbicide candidate” (PI Roan)
NIH R21 AI122821 “Characterization of exosomes from semen of uninfected and HIV-infected men” (PI Roan)
NIH P50 HD055764 “Origins and biological consequences of human infertility” (PI Giudice)
NIH R15 GM123447 "Molecular basis of adaptation in seminal proteins of human and other primates" (PI Jensen-Seaman)
NIH R00 “Exploring the role of semen amyloids in promoting HIV infection and fertilization” (PI Roan)

Selected Publications related to Project

1. Marques de Menezes E.G., Jang K., George A.F., Nyegaard M., Neidleman J., Inglis H.C., Danesh A., Deng X., Afshari A., Kim Y.H., Billaud J., Marson K., Pilcher C.D., Pillai S.K., Norris P.J., Roan N.R. Seminal plasma-derived extracellular vesicle fractions from HIV-infected men exhibit unique miRNA signatures and induce a pro-inflammatory response in cells isolated from the female reproductive tract. 2020. Journal of Virology

2. George A.F., Jang K.S., Nyegaard M., Neidleman J., Spitzer T.L., Xie G., Chen J.C., Herzig E., Laustsen A., Marques de Menezes E.G., Houshdaran S., Pilcher C.D., Norris P.J., Jakobsen M.R., Greene W.C., Giudice L.C., Roan N.R. Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling. 2020. Human Reproduction

3. Chen J.C., Johnson B.A., Erikson D.W., Piltonen T.T., Barragan F., Chu S., Kohgadai N., Irwin J.C., Greene W.C., Giudice L.C., Roan N.R. Seminal plasma induced global transcriptomic changes associated with cell migration, proliferation, and viability in endometrial epithelial cells and stromal fibroblasts. 2014. Human Reproduction

4. Usmani S.M., Zirafi O.Z., Müller A.J., Sandi-Monroy N., Yadav J.K., Meier C., Weil T., Roan N.R., Greene W.C., Walther P., Nilsson K.P.R., Hammarström P., Wetzel R., Pilcher C.D., Gagsteiger F., Fändrich M., Kirchhoff F., Münch J. Direct Visualization of HIV-enhancing endogenous amyloid fibrils in human semen. 2014. Nature Communications

5. Bergman P., Roan N.R., Römling U., Bevins C.L., Münch J. Amyloid formation: functional friend or fearful foe? 2016. J Intern Med

6. LoRicco J.G., Xu C.S., Neidleman J., Bergkvist M., Greene W.C., Roan N.R.*, Makhatadze G.I.* Gallic acid is an antagonist of semen amyloid fibrils that enhance HIV-1 infection. *Co-corresponding authors. 2016. J Biol Chem

7. Roan N.R., Sandi-Monroy N., Kohgadai N., Usmani S.M., Hamil K.G., Neidleman J., Montano M., Standker L., Rocker A., Cavrois M., Rosen J., Marson K., Smith J.F., Pilcher C.D., Gagsteiger F., Sakk O., O’Rand M., Lishko P.V., Kirchhoff F., Münch J., Greene W.C. Semen amyloids participate in human spermatozoa selection and clearance. 2017. Elife

8. Müller J.A., Harms M., Krüger F., Groß R., Joas S., Hayn M., Dietz A.N., Lippold S., von Einem J., Schubert A., Michel M., Mayer B., Cortese M., Jang K.S., Sandi-Monroy N., Deniz M., Ebner F., Vapalahti O., Otto M., Bartenschlager R., Herbeuval JP, Schmidt-Chanasit J., Roan N.R., Münch J. Semen inhibits Zika virus infection of cells and tissues from the anogenital region. 2018. Nature Communications