Epididymis-specific RNase A family genes regulate fertility and small RNA processing.

How Does a Father's Lifestyle Impact His Offspring's Health? Researchers in the Sharma Lab are exploring a fascinating question: can a father's lifestyle—like diet, physical activity, or environmental exposures—affect the health of his children? Beyond the genes passed through DNA, there's another layer of information called epigenetic information, which might hold the answer. We are particularly focused on sperm, which carries more than just DNA. Tiny molecules like small RNAs in sperm may act as messengers of a father's lifestyle to his offspring. One big mystery is how these small RNAs are created and if they’re influenced by lifestyle factors. To investigate, the researchers studied a group of proteins in the epididymis (an organ where sperm matures) called RNase 9-12. Using genetically modified mice missing these proteins, they discovered two key findings: 1. Small RNA and Infertility: The absence of RNase 9-12 disrupted the production of small RNAs in sperm. These knockout mice had fewer small RNA fragments compared to normal mice. 2. Reduced Sperm Motility: The knockout mice also showed reduced sperm movement, linked to lower levels of a critical protein called ADAM3. This made them infertile in natural mating, as their sperm couldn’t reach the right spot in the female reproductive tract. Interestingly, these sperm could still fertilize eggs through in vitro fertilization, highlighting a specific motility issue. These results are exciting because they shed light on how a father’s environment and biology might influence sperm function and fertility. The Sharma Lab is now working to uncover more about the role of these proteins and how they help regulate sperm’s small RNA cargo. This research could eventually reveal new ways that lifestyle choices are biologically passed from one generation to the next.