- Amyloid fibrils
found in protein mis-folding diseases have a normal function in reproductive
amyloid fibrils found in seminal that are
known to enhance HIV infection also regulate phagocytosis of damaged
- Targeting fibrils
for the development of HIV microbicide may hinder natural sperm selection
Seminal plasma or fluid consists of several proteins and
recently has been identified to contain protein aggregates called amyloid
. These are protein fragments known to enhance HIV
sexually transmitted viral infections by promoting fusion of viruses to the
cellular targets. However a recent study provides evidence to their
physiological function. Published in eLIFE,
the study signifies the role
of amyloid fibrils in apoptosis or phagocytosis of damaged spermatozoa.
‘Amyloid fibrils present in the seminal fluid plays an important role in entrapping spermatozoa and promoting phagocytosis of damaged ones.’
protein fragments that form aggregates in the seminal fluid. Generally found in
diseases that are caused as a result of protein mis-folding, they have also
been identified in the semen of healthy men. Until now the seminal plasma is
the only known human biological fluid to contain endogenous amyloid fibrils.
Previously known to only enhance HIV
, it is now evident that they also play a vital role in selective
inhibition of damaged spermatozoa.
Determination of physiological role of amyloid fibrils
The similarities between HIV fusion to host cell and sperm
fusion to oocyte led researches to hypothesize that fibrils promote
fertilization. When this was tested through success rates of in
or IVF, it was observed that the physiologically
present concentrations of fibrils suppressed IVF. When live cell imaging was
performed to understand the mechanism in mice, it was noticed that the fibrils
prevented sperm fusion to the oocyte by entrapping the spermatozoa. The same was indicative of human spermatozoa on computer
assisted sperm analysis (CASA).
The entrapment is facilitated by limiting the motility of the
sperm either partially or completely. On further studying the characteristics
of the entrapped spermatozoa, it was noted that semen amyloids predominantly
entrap sperms that are morphologically abnormal or defective. The research team
was also able to conclude that the entrapped sperms are preferentially and
efficiently degraded by the immune cells in the female reproductive tract
Applications based on the newly hypothesized function of
multiple sperms from fertilizing the egg, in case of which increased
polyploidy may effect embryonic development negatively.
as a quality controller to ensure only the fittest sperm reaches the site
manufacturers must consider the positive role of amyloid fibrils in
reproductive biology before developing HIV microbicides (for STD
prevention) that target the fibrils present in the semen.
- Nadia R Roan, Nathallie Sandi-Monroy, Nargis Kohgadai,Shariq M Usmani, Katherine G Hamil, Jason Neidleman, Mauricio Montano, Ludger Ständker, Annika Röcker, Marielle Cavrois, Jared Rosen, Kara Marson, James F Smith, Christopher D Pilcher, Friedrich Gagsteiger, Olena Sakk, Michael O'Rand, Polina V Lishko, Frank Kirchhoff, Jan Münch, Warner C Greene. (2017) Semen amyloids participate in spermatozoa selection and clearance. doi:10.7554/eLife.24888
- Semen amyloids participate in spermatozoa selection and clearance - (https:elifesciences.org/articles/24888)