Taste genes linked to male fertility

Taste and fertility may seem like two completely unrelated areas, but according to scientists at the Monell Chemical Senses Center, two proteins involved in oral taste detection also play an important role in sperm development.

In a paper published in the Proceedings of the National Academy of Sciences, the researchers noted that TAS1R3, a component of both the sweet and umami (amino acid) taste receptors, and GNAT3, a molecule needed to convert the oral taste receptor signal into a nerve cell response, are “strongly expressed in testis and sperm, but their functions in these tissues were previously unknown.”

These functions became known when the researchers were breeding mice for taste-related studies. They were unable to produce offspring that were simultaneously missing the two taste-signalling proteins, with fertility being affected in the males.

The research team then engineered mice that were missing genes for the mouse versions of TAS1R3 and GNAT3 but expressed the human form of the TAS1R3 receptor; these mice were fertile. But when the human TAS1R3 receptor was blocked in the mice by adding the drug clofibrate to their diet, thus leaving the mice without any functional TAS1R3 or GNAT3 proteins, the males became sterile due to malformed and fewer sperm. The sterility was reversed after clofibrate was removed from the diet.

Previous Monell studies have shown that clofibrate is a potent inhibitor of the human TAS1R3 receptor. It also belongs to a class of drugs (fibrates) that are often prescribed to treat lipid disorders such as high blood cholesterol. Meanwhile, the structurally related phenoxy herbicides, used in agriculture, also block the human TAS1R3 receptor. With the new findings in mind, the paper’s lead author, Dr Bedrich Mosinger, speculates that these compounds could be negatively affecting human fertility.

The next step, says co-author Dr Robert Margolskee, is to “identify the pathways and mechanisms in testes that utilise these taste genes so we can understand how their loss leads to infertility.” But although he says the findings currently “pose more questions than answers,” they are expected to provide immense assistance in the field of reproduction. Not only could low sperm quality (as a result of fibrates and phenoxy compounds) be treated, but it could also be deliberately kept down as a form of contraception.