Maternal stress retards fetal development in mice with transcriptome-wide impact on gene expression profiles of the limb

Abstract

The environment of a pregnant mother has a life-long impact on later life of offspring. Maternal stress is known to cause low birth weight and programs several physiological dysfunctions in offspring. However, the direct effects of maternal stress on the developing fetus remain largely unknown. The present study focused on the effect of chronic maternal stress on the developmental program and its molecular mechanisms. Pregnant mice were given 6-hour immobilization stress every day from 8.5 days post coitum. Fetal body weight was significantly decreased by maternal stress throughout development. Importantly, developmental events were retarded in the stressed fetuses. Around embryonic day 13.5 (E13.5), the developmental increment of somite numbers was delayed, although this difference recovered by E15.5. Limb bud formation and regression of interdigital webbing were also retarded by approximately 0.5 days. Subsequently, transcriptomes of developing limbs were analyzed by cDNA microarrays. Approximately, one-tenth of detected transcripts were significantly influenced by maternal stress. Q-PCR AQ analyses further demonstrated that the expression of a subset of limb development-associated genes, including Igf1, Aldh1a2, and Acta1, was changed in the stressed fetus. In conclusion, our findings suggest that maternal stress can retard limb and somite development in mice, with profound impacts on the developmental genetic program of limb.

Keywords::

• Maternal stress
• environmental programing
• embryonic development
• developmental retardation
• gene expression
• growth retardation

Acknowledgements

This work was supported by the Korea Ministry of Education, Science, and Technology (MEST) through the Brain Research Center of the 21st Century Frontier Research Program, and by the National Research Foundation of Korea (NRF; 2010-0020566). H. K. Choe and S. Chung were supported by Brain Korea 21 Research Fellowships from the Korea MEST.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.