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Credit: University of Texas at San Antonio
Millions of couples who have difficulty conceiving can be relieved by new research being conducted by scientists from the University of Texas at San Antonio. The researchers developed a high-resolution genetic map showing how men produce sperm. Their efforts could help solve genetic problems related to male fertility, a major cause of design problems.
The researchers' findings reveal detailed information about genes that are turned on or off in stem cells that eventually turn into spermatozoa. These data could provide physicians with a crucial insight into sperm development in a patient, a perspective that was lacking until now.
Brian Hermann, a researcher at UTSA, believes that this new knowledge could change the game by revealing what can go wrong in men with infertility.
"We have adopted a new forward-thinking approach up to the level of individual cells to understand all the changes in which genes are used to make sperm in the testes." This had not been possible before and prevented progress toward treating male infertility, "said Hermann, a professor of biology and director of the UTSA Center for Genomics.
The results appear in the November 6 edition of the scientific journal, Cell reports. Professors Hermann and John R. McCarrey led the group, which included researchers from UTSA and from across the country.
Together, the team has built a comprehensive digital library of cell types needed for sperm production in mice and humans. They examined more than 62,000 cells and identified 11 different gene expression profiles; their work even led to the discovery of rare and new cells for which little data had previously been reported. The research, which began in early 2014, was funded by the Kleberg Foundation, the Hurd Foundation, and the National Institutes of Health (NIH).
According to the NIH, reproductive problems in men contribute to at least half of the cases of infertility in couples. Many cases of male infertility are treated with medication. Some even require surgery. Yet in nearly half of these same cases, the reasons for male infertility are unknown.
The UTSA digital roadmap was constructed using the sequencing of genes expressed in germ cells. The researchers used high-tech machines that allow scientists to examine tens of thousands of individual cells and produce the gene library expressed in each cell in one to two days. The method also used advanced bioinformatics, data analysis to decode gene expression data generated from cells.
The UTSA's individualized approach to profiling gene expression at a cell level is what makes this work different. The previous methods were based on cell group analysis, but when grouped into experiments, the differences between the individual cells are averaged and thus obscured. Therefore, the new UTSA approach provides important data that can help discover the biology underlying how sperm is produced and what can go wrong in men with infertility.
"That's how we find the needles in the haystack," Hermann said. "We were not previously able to separate different cells with different functions, so in order to understand exactly how they are different, we looked at individual cells instead of the conventional method of grasping them all in different ways. block as a group. "
UTSA's new digital gene expression library offers many scientific applications. This could help improve clinical diagnoses in men with infertility because their "signatures" of gene expression will be different from those of normal men now described in this new database. The UTSA resource can also provide a foundation to help innovate the next generation of male contraception and even potentially develop sperm outside the body.
The researchers hope that the methodology can also be applied to other biological processes in the body to discover new information on which to base new approaches to diagnose, treat or prevent a wide variety of diseases.
"It has been decades since we dreamed of taking the most primitive cells of the testicle and converting them into sperm in a petri dish, but that never worked," Hermann said. "If anyone wants to generate sperm in a box, he wants to know how similar these cells are to those found naturally in the body." The data we generated now provides a library of references for purposes comparison. "
Explore further:
One study describes a drug that could prevent infertility in cancer patients
More information:
Brian P. Hermann et al., The Unicellular Transcriptome of Spermatogenesis in Mammals, Spermatogonial Stem Cells to Spermatids, Cell reports (2018). DOI: 10.1016 / j.celrep.2018.10.026
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