High-temperature exposure during the early embryonic stage lowers core body temperature after growth via a hypothalamic Igfbp2-dependent mechanism

The mechanisms underlying individual differences in core body temperature (T_c) are unexplained by genetic factors and poorly understood. Here, we investigated whether the environmental temperature during early development affects postnatal T_c. Mouse embryos were cultured from pronuclear to blastocyst stage in either standard (37 °C) or high (38 °C) temperature, and the T_c of each grown-up adult was measured. The adult 38 °C-incubated mice showed lower T_c than the 37 °C group without changes in activity levels. In the hypothalamus of the 38 °C group, insulin-like growth factor 1 (Igf1) and IGF binding protein 2 (Igfbp2) gene expression increased. The decrease in T_c in the wild-type 38 °C group was alleviated by brain neuron-specific Igfbp2 knockout. This suggests that IGFBP2 binds to IGF-1 and, inhibits its binding to the receptor, thereby interfering with the thermogenic signaling of IGF-1. These results suggest that one of the factors determining individual postnatal T_c is the ambient temperature of embryos at an early developmental stage, which could affect epigenetic changes, such as DNA methylation, leading to alterations in the Igf1 and Igfbp2 gene expressions in adulthood.