Maternal exposure to high temperature in fish induces intergenerational emotional and cognitive disorders, associated with dysregulation of neurodevelopment genes in eggs and progeny

Female fish are known to be sensitive to temperature during reproduction, but the long-term consequences on offspring adaptive behaviour and their underlying intergenerational mechanisms remain unknown. We studied the intergenerational consequences of female rainbow trout (Oncorhynchus mykiss) exposure to high (17°C) or normal temperature (12°C) on offspring behavioural phenotypes. We also analysed genome-wide gene expression in eggs and embryos to elucidate the mechanisms by which thermal maternal exposure impacts offspring behaviour. Here we show that a thermal maternal stress induces emotional and cognitive disorders in offspring. Fear responses to a novel environment were inhibited in 17°C offspring indicating global emotional blunting. Thermal stress in mothers also decreased spatial learning abilities in progeny. Behavioural phenotypes were associated with the dysregulation of several genes known to play major roles in neurodevelopment. This is especially true for auts2, a key gene for neurodevelopment in fish and mammals, more specifically neuronal migration and neurite extension, and critical for the acquisition of neurocognitive function in fish and mammals. In addition to auts2, our analysis revealed the dysregulation of another neurodevelopment gene (dpysl5) as well as genes associated with human cognitive disorders (arv1, plp2). Our study also revealed major differences in maternal mRNA abundance in the eggs following maternal exposure to high temperature indicating that some of the observed intergenerational effects are mediated by maternally-inherited mRNAs accumulated in the egg. Together, our observations shed new light on the intergenerational determinism of fish behaviour and associated underlying mechanisms. They also stress the importance of maternal history on fish adaptive capacities in a context of global climate changes. Two-year old females rainbow trout were exposed to either 12°C (12°C group, standard reproduction conditions) or 17°C (17°C group, high suboptimal temperature) for six weeks before ovulation. The temperature of 17°C was selected because it is known to induce a dramatic decrease in embryonic survival {Aegerter, 2004 #2630}. For each group, 30 marked (external tag placed on the dorsal fin) females were kept in 2.5 m3 tanks (2 x 2 x 0.62 m, length × width × water height). In the 17°C group, females initially reared at 12°C were acclimated for five days to an increase of 1°C/day until 17°C. For three weeks preceding ovulation, females were checked every two-three days to detect ovulation. In both experimental group, eggs originating from four simultaneously ovulating females of each group were collected and fertilized using a pool of sperm collected from four males held at 12°C. Fertilization was performed immediately in both groups in order to avoid any bias on subsequent behavioural phenotypes that would have been induced by differences during embryo development. For each of the eight females, fertilizations of 800 eggs were performed at 10°C using the medium ActiFish (IMV, L'Aigle, France; 100 ml ActiFish + 400 ml water) and fertilized eggs were distributed within a tray (20 x 50 cm) in two incubators (10 x 10 cm) (approximately 400 eggs/incubator and two incubators/tray) supplied with 10°C flow-though recycled water. Each tray was covered with a lid to avoid exposure to light.