A Critical Enzyme For Sperm Formation Could Be A Target For Treating Male Infertility
Arthur T Knackerbracket has found the following story:
While some of our body's cells divide in a matter of hours, the process of making sperm, meiosis, alone takes about 14 days from start to finish. And fully six of those days are spent in the stage known as the pachytene, when pairs of chromosomes from an individual's mother and father align and connect.
"This stage is really important, because the pair needs to be aligned for the exchange of genetic material between those two chromosomes," says P. Jeremy Wang, a biologist in Penn's School of Veterinary Medicine. "If anything goes wrong at this stage, it can cause a defect in meiosis and problems in the resulting sperm, leading to infertility, pregnancy loss, or birth defects."
In a new paper in Science Advances, Wang and colleagues have identified an enzyme that plays a crucial role in maintaining this chromosomal pairing during the pachytene stage of meiosis. Without this protein, named SKP1, meiosis cannot proceed to metaphase, the next major developmental stage involved in generating sperm cells.
The finding may help overcome hurdles that have stood in the way of treating certain forms of male infertility, in which a man makes no sperm but in whom sperm's precursor cells, spermatogonia, can be found.
"Reproductive technologies like in vitro fertilization have made a huge difference for infertile patients, but the male needs to have at least some sperm," says Wang. "If the male has no sperm, then the only option is to use donor sperm. But if you can find these spermatogonia, the pre-meiotic germ cells, they could be induced to go through meiosis and make sperm. So SKP1 could be part of the solution to ensuring meiosis continues."
Wang is also hopeful that his finding could aid in basic research on sperm development that his and many other labs pursue. "Right now we use animals to do our research; we don't have a cell culture system to produce sperm," he says. "Manipulating SKP1 and the pathway in which it acts could allow us to set up an in vitro system to produce sperm artificially, which would be a boon for our studies."
[...] "Now that we know SKP1 is required, we're looking for the proteins it interacts with upstream and downstream so we can study this pathway," says Wang.
Journal Reference:
Yongjuan Guan, N. Adrian Leu, Jun Ma, LukiA Chmital, Gordon Ruthel, Jordana C. Bloom, Michael A. Lampson, John C. Schimenti, Mengcheng Luo, P. Jeremy Wang. SKP1 drives the prophase I to metaphase I transition during male meiosis. Science Advances, 2020; 6 (13): eaaz2129 DOI: 10.1126/sciadv.aaz2129
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