09 Jun Possible Sperm Related Cause of Male Infertility Identified
MedicalResearch.com Interview with:
Tomer Avidor-Reiss, Ph.D.
Professor, College of Natural Sciences and Mathematics
Department of Biological Sciences
University of Toledo
Toledo, OH 43606
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Most dividing cells in the body need exactly two centrioles for normal cell division and development. Abnormalities in centriole number can cause cancer and devastating developmental defects. Because of this importance of centriole number and because all cells originate from the zygote – the product of the sperm and egg – it makes sense that the zygote should possess two centrioles, as well.
However, the egg does not contain any centrioles, so the sperm is the sole contributor of the centrioles; and yet, it is currently thought that the sperm contains only one centriole. This is problematic because supposedly that leaves the zygote with only one centriole, even though it must propagate cells with two centrioles. In the past, we found that insect sperm have an atypical centriole that escaped discovery because it is so different. We therefore hypothesized that humans may also have an atypical sperm centriole.
Our new paper shows that in human sperm there exists, in addition to the known centriole, a second centriole that deviates from the typical structural and composition that is expected from a centriole. Although it looks very different from any centriole ever described, we found that it functions in an in vitro functional assay. Furthermore, during fertilization, it performs the functions traditionally associated with centrioles. Together, this resolves a 50-year-long debate regarding the centrioles of human sperm; the sperm contains two functional centrioles, despite that one is atypical.
MedicalResearch.com: What should readers take away from your report?
Response: The sperm has two functional centrioles, which is more consistent with what we have seen across evolution. Across evolution, from flies and beetles to cattle and humans, the sperm contains two centrioles, despite that their structure varies. This shows that centrioles can deviate from their traditional structure and still perform their typical functions.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: This work opens a lot of doors regarding the diagnostics and treatments of infertility, spontaneous abortion and developmental diseases. Our previous work in fruit flies shows that defects in a similar atypical centriole causes infertility and developmental delays, and together with our most recent work, this suggests that the human atypical centriole may be instrumental in many reproductive diseases. Interestingly, we think that men with defects in this structure may fall into the “idiopathic infertile couple” diagnosis, and therefore may not have any viable treatments available to them. Furthermore, intracytoplasmic sperm injection (ICSI), the most common treatment for male infertility, may not necessarily overcome defects in the atypical centriole. In order to investigate this, we look forward to examining the atypical centriole in men who fall into different fertility diagnoses to determine if defects are correlated with certain types of infertility. If the atypical centriole is implicated in infertility, it may be possible to approach new therapies for these couples, such as pharmaceuticals or the new three-parent baby approach.
In addition, because this atypical centriole is responsible for nucleating the sperm’s tail, and because it is unique to the sperm, this atypical centriole may be an interesting target for contraception research.
MedicalResearch.com: Is there anything else you would like to add?
Response: This work started with an unexpected observation during basic research in flies demonstrating the importance of using simple model animals to assist in human medicine.
This work has been possible due to a large network of inquisitive and determined collaborators spanning four states and two countries, in addition to the centrosome, cytoskeleton and reproductive biology communities. Furthermore, super-resolution microscopy (HyVolution, SIM, STED, and STORM), correlative light and electron microscopy, high pressure freeze substitution microscopy, in vitro fertilization, and in vitro functional assays were crucial for this discovery. This work shows that impactful research requires teamwork and cutting-edge methods.
Emily L. Fishman, Kyoung Jo, Quynh P. H. Nguyen, Dong Kong, Rachel Royfman, Anthony R. Cekic, Sushil Khanal, Ann L. Miller, Calvin Simerly, Gerald Schatten, Jadranka Loncarek, Vito Mennella, Tomer Avidor-Reiss. A novel atypical sperm centriole is functional during human fertilization. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04678-8
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