Semen amyloids participate in spermatozoa selection and clearance

Author:

Roan Nadia R12ORCID,Sandi-Monroy Nathallie34,Kohgadai Nargis12,Usmani Shariq M5,Hamil Katherine G6ORCID,Neidleman Jason12,Montano Mauricio2,Ständker Ludger37,Röcker Annika3,Cavrois Marielle28,Rosen Jared9,Marson Kara10,Smith James F1,Pilcher Christopher D10,Gagsteiger Friedrich4,Sakk Olena11,O’Rand Michael6,Lishko Polina V9ORCID,Kirchhoff Frank3,Münch Jan3,Greene Warner C2812

Affiliation:

1. Department or Urology, University of California San Francisco, San Francisco, United States

2. Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, United States

3. Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

4. Kinderwunsch-Zentrum, Ulm, Germany

5. The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, United States

6. Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, United States

7. Core Facility Functional Peptidomics, Ulm University, Ulm, Germany

8. Department of Medicine, University of California San Francisco, San Francisco, United States

9. Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, United States

10. HIV / AIDS Division, San Francisco General Hospital, University of California San Francisco, San Francisco, United States

11. Core Facility Transgenic Mice, Medical Faculty, Ulm University, Ulm, Germany

12. Department of Microbiology and Immunology, University of California, San Francisco, United States

Abstract

Unlike other human biological fluids, semen contains multiple types of amyloid fibrils in the absence of disease. These fibrils enhance HIV infection by promoting viral fusion to cellular targets, but their natural function remained unknown. The similarities shared between HIV fusion to host cell and sperm fusion to oocyte led us to examine whether these fibrils promote fertilization. Surprisingly, the fibrils inhibited fertilization by immobilizing sperm. Interestingly, however, this immobilization facilitated uptake and clearance of sperm by macrophages, which are known to infiltrate the female reproductive tract (FRT) following semen exposure. In the presence of semen fibrils, damaged and apoptotic sperm were more rapidly phagocytosed than healthy ones, suggesting that deposition of semen fibrils in the lower FRT facilitates clearance of poor-quality sperm. Our findings suggest that amyloid fibrils in semen may play a role in reproduction by participating in sperm selection and facilitating the rapid removal of sperm antigens.

Funder

National Institutes of Health

U.S. Department of Defense

Deutsche Forschungsgemeinschaft

European Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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