Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation

Abstract

Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8°C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecularmechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockoutmouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germcell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.-Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A.D., Lemonnier, L.,De Clerck, T., Bokhobza, A., Derouiche, S.,Dewailly, E., Slomianny, C., Mauduit,C., Benahmed,M., Roudbaraki,M., Jegou,B., Prevarskaya, N.,Bidaux, G. Cold/mentholTRPM8receptors initiate thecold-shockresponseandprotect germcellsfromcold-shock-inducedoxidation.