RESEARCHERS have developed a novel preclinical model that could accelerate the development of non-hormonal male contraceptives by demonstrating that a human fertility gene can rescue infertility in mice. The study focused on two testis-specific serine proteases—PRSS55 and TMPRSS12—both essential for male fertility in mice.
Using genetic engineering, scientists created transgenic mouse lines that express human PRSS55 or TMPRSS12 on infertile knockout backgrounds. Strikingly, human PRSS55—especially when modified with an intracellular 3xFLAG tag—successfully restored male fertility, with RES TM males producing offspring at levels comparable to healthy controls. This suggests that human PRSS55 can functionally substitute for its mouse counterpart and supports the use of the RES TM line as a reliable model for testing potential contraceptives targeting PRSS55.
However, the results were less promising for TMPRSS12. Despite successful mRNA expression, the human version of this gene failed to rescue fertility, with transgenic males showing impaired sperm motility and function. This outcome may be linked to differences in protein function between species or technical limitations in protein expression.
Overall, the study offers a critical step forward in contraceptive science by providing a validated animal model to test non-hormonal approaches targeting human sperm-specific proteins.
Reference
Sutton CM et al. Rescue of male infertility by human PRSS55 in transgenic mice establishes a contraceptive research model. Sci Rep. 2025;DOI: 10.1038/s41598-025-09604-9.
