When breeding mice for taste-related studies, researchers at Philadelphia’s Monell Center were surprised to find they were unable to produce offspring that were simultaneously missing two taste-signaling proteins, TAS1R3 and GNAT3.
Writing today in the Proceedings of the National Academies of Sciences (PNAS), Monell’s Bedrich Mosinger, M.D., Ph.D., and his colleagues show that TAS1R3—a component of both the sweet and umami taste receptors—and GNAT3—which helps to convert the oral taste receptor signal into a nerve cell response—play a “crucial role in sperm development.”
“This paper highlights a connection between the taste system and male reproduction,” Dr. Mosinger said in a statement. “It is one more demonstration that components of the taste system also play important roles in other organ systems.”
Dr. Mosinger and his colleagues had previously shown that some taste genes could play functional roles in the stomach, intestines, pancreas, lungs, and brain, among other sites. But until now, these genes had never been associated with male reproduction.
Surprised by their finding that inactivation of TAS1R3 and GNAT3 caused sterility in male mice, the researchers proceeded to create new models. When they engineered mice missing genes for the murine versions of TAS1R3 and GNAT3, but which expressed the human form of the TAS1R3 receptor, they found the animals were fertile.
By adding the drug clofibrate to the animals’ diet, the human TAS1R3 receptor was blocked, and the animals became sterile because of fewer and malformed sperm. This sterility, the researchers note, was swiftly reversed once clofibrate—which belongs to a class of drugs that frequently are prescribed to treat lipid disorders such as high blood cholesterol or triglycerides —was removed from the animals’ diet.
As a result, Dr. Mosinger et al., suggested the common use of fibrates in modern medicine could be one factor contributing to rising rates of human male infertility.
“Like much good science, our current findings pose more questions than answers," said Monell’s Robert Margolskee, M.D., Ph.D., co-author on the study. "We now need to identify the pathways and mechanisms in testes that utilize these taste genes so we can understand how their loss leads to infertility."
“Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility” appeared online in PNAS July 1.