Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.
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 molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse 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 germ cell 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., Jégou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Anne-Sophie
AS
Borowiec
Pharmacologie Fondamentale et Clinique de la Douleur, INSERM, U1107, Neuro-Dol, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France;
Benoit
B
Sion
INSERM, U1085-Irset, Campus de Beaulieu, Rennes, France;
Frédéric
F
Chalmel
INSERM, U1085-Irset, Campus de Beaulieu, Rennes, France;
Antoine
A
D Rolland
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Loïc
L
Lemonnier
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Tatiana
T
De Clerck
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Alexandre
A
Bokhobza
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Sandra
S
Derouiche
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Etienne
E
Dewailly
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Christian
C
Slomianny
Centre Méditerranéen de Médecine Moléculaire (C3M), Team 5, INSERM, U1065, Nice, France; and.
Claire
C
Mauduit
Centre Méditerranéen de Médecine Moléculaire (C3M), Team 5, INSERM, U1065, Nice, France; and.
Mohamed
M
Benahmed
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Morad
M
Roudbaraki
INSERM, U1085-Irset, Campus de Beaulieu, Rennes, France;
Bernard
B
Jégou
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France;
Natalia
N
Prevarskaya
Physiologie Cellulaire (PHYCEL), INSERM, U1003, Université Lille, Lille, France; Laboratoire de Physique des Lasers, Atomes et Molécules (PhLAM), UMR8523, Biophotonic Team, Villeneuve d'Ascq, France gabriel.bidaux@univ-lyon1.fr.
Gabriel
G
Bidaux
D000818:Animals; D003080:Cold Temperature; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000502:physiology*
D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C492297:TRPM8 protein, mouse
apoptosis; hypothermia; spermatogenesis