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

Dr. Avidor-Reiss

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.  Continue reading

Step Closer To Treating Mitochondrial Diseases by Understanding How Embryos Digest Sperm

MedicalResearch.com Interview with:

Peter Sutovsky PhD Professor of Animal Science in the College of Agriculture, Food and Natural Resources University of Missouri Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine University of Missouri Health System

Dr. Peter Sutovsky

Peter Sutovsky PhD
Professor of Animal Science in the College of Agriculture, Food and Natural Resources
University of Missouri
Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine
University of Missouri Health System

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Strictly maternal inheritance of mitochondria, the cellular power stations, and mitochondrial genes that mitochondria harbor, is a major biological paradigm in mammals. Propagation of paternal, sperm-contributed mitochondrial genes, resulting in a condition called heteroplasmy, is seldom observed in mammals, due to post-fertilization elimination sperm mitochondria, referred to as “sperm mitophagy.” Our and others’ recent results suggest that this process is mediated by the synergy of ubiquitin–proteasome system (UPS) pathway that recycles outlived cellular proteins one molecule at a time, and autophagic pathway capable of engulfing and digesting an entire mitochondrion.

Here we demonstrate that the co-inhibition of the ubiquitin-binding autophagy receptor proteins SQSTM1, GABARAP, and UPS, and the UPS protein VCP dependent pathways delayed the digestion of sperm mitochondria inside the fertilized pig egg. By manipulating said proteins, we created heteroplasmic pig embryos with both the paternal and maternal mitochondrial genes. Such animal embryos that could be used as a biomedical model to research and alleviate certain forms of mitochondrial disease.

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Making sperm from stem cells in a dish

Researchers have found a way to turn mouse embryonic stem cells into sperm. This finding, reported in the journal Cell in a special online release on August 4th, opens up new avenues for infertility research and treatment. A Kyoto University team has coaxed mouse embryonic stem cells into sperm precursors, called primordial germ cells (PGCs), and shown that these cells can give rise to healthy sperm. The researchers say that such in vitro reconstitution of germ cell development represents one of the most fundamental challenges in biology.

When transplanted into mice that were unable to produce sperm normally, the stem cell derived PGCs produced normal-looking sperm, which were then used to successfully fertilize eggs. These fertilized eggs, when transplanted into a recipient mother, produced healthy offspring that grew into fertile male and female adult mice. The same procedure could produce fertile offspring from induced pluripotent stem cells that are often derived from adult skin cells.

“Continued investigations aimed at in vitro reconstitution of germ cell development, including the induction of female PGCLCs and their descendants, will be crucial for a more comprehensive understanding of germ cell biology in general, as well as for the advancement of reproductive technology and medicine,” the researchers wrote.