A new study has identified a crucial enzyme, SKP1, that plays an essential role in the process of sperm development. The enzyme helps maintain chromosomal pairing during meiosis, the cell division process that produces sperm. This discovery could provide a breakthrough in treating certain types of male infertility, particularly in cases where men produce no sperm but still have sperm precursor cells, known as spermatogonia.
Meiosis, which takes about 14 days, includes a stage called pachytene, lasting about six days. During this time, chromosome pairs from the mother and father align and connect. In their study, researchers led by Wang found that SKP1 is vital for this alignment to continue. Without it, meiosis cannot proceed to the next stage, metaphase, where chromosomes are prepared for division.
Wang, a lead researcher in the study, highlighted that SKP1’s role in maintaining chromosomal integrity during meiosis could help treat male infertility. “Reproductive technologies like in vitro fertilization have been a game-changer, but they require sperm. If no sperm is present, donor sperm is the only option. However, if spermatogonia are available, they could be induced to undergo meiosis and produce sperm,” he said.
Wang also believes the discovery could help advance research into sperm development. Currently, scientists use animal models for such studies, as there is no cell culture system for producing sperm. “Manipulating SKP1 and understanding its role could lead to an in vitro system for creating sperm, which would significantly aid our research,” Wang added.
The study, published in Science Advances, is the result of nearly a decade of work led by Wang’s postdoctoral researcher, Yongjuan Guan, with support from former postdoc Mengcheng Luo. The team began focusing on SKP1 after screening for proteins in the area where chromosomes align during the pachytene stage of meiosis.
Prior research had shown that SKP1 is vital for cell division in all cells, not just in sperm and eggs. To study its role, the researchers created a mouse model where SKP1 could be turned off specifically in germ cells during adulthood. Without SKP1, the chromosomes in germ cells separated too early, preventing proper meiosis.
The team also explored SKP1’s role in female cells. They found that SKP1 is necessary for oocytes, the cells that develop into eggs, to maintain chromosome alignment. Oocytes without SKP1 developed misaligned chromosomes and many were eventually lost.
Looking forward, Wang and his team plan to explore how SKP1 interacts with other proteins to understand how it ensures the proper progression of meiosis. Their ultimate goal is to develop potential strategies for treating infertility and creating innovative lab techniques.
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