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

Sci Rep. 2024 Dec 3;14(1):29586. doi: 10.1038/s41598-024-80252-1.

Abstract

The mechanisms underlying individual differences in core body temperature (Tc) are unexplained by genetic factors and poorly understood. Here, we investigated whether the environmental temperature during early development affects postnatal Tc. Mouse embryos were cultured from pronuclear to blastocyst stage in either standard (37 °C) or high (38 °C) temperature, and the Tc of each grown-up adult was measured. The adult 38 °C-incubated mice showed lower Tc 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 Tc 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 Tc 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.

Keywords: Core body temperature; IGF binding protein 2; Insulin-like growth factor 1.

MeSH terms

  • Animals
  • Body Temperature
  • Embryo, Mammalian / metabolism
  • Embryonic Development / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Hot Temperature
  • Hypothalamus* / embryology
  • Hypothalamus* / metabolism
  • Insulin-Like Growth Factor Binding Protein 2* / genetics
  • Insulin-Like Growth Factor Binding Protein 2* / metabolism
  • Insulin-Like Growth Factor I* / genetics
  • Insulin-Like Growth Factor I* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor I