No Evidence of Impact of Genetic Sex on Hyperthermia-Induced Neural Tube Defects in Chicken Embryos

In mammals, cranial neural tube defects (NTDs) are more likely to occur in females. It has been proposed that the sex bias in NTDs was due to the presence of the inactive X chromosome in the somatic cells of female embryos and that the inactive X acted as a heterochromatic sink, competing for silencing factors with the rest of the genome. Such competition increased the likelihood of abnormal gene regulation. To test this hypothesis, we used an animal model that lacks dosage compensation, the chicken Gallus gallus. If the heterochromatic sink hypothesis was correct, no sex bias will be found in chicken embryos with cranial NTDs.

We used in ovo heat treatment to induce NTDs in chicken embryos and PCR genotyping to determine embryos' genetic sex. Embryo phenotypes were examined using a dissecting microscope. Embryos were staged according to Hamburger and Hamilton criteria and scored for NTDs.

We observed a statistically significant increase in NTDs following heat treatment (38.1% in the treatment group vs. 5.9% in the control group), but no sex bias. Next, we asked if heat treatment led to a developmental delay and found a significant association between the numbers of somite pairs and heat treatment and a reduced number of somites in the chicken embryos with cranial NTDs.

In ovo hyperthermia during the developmental window when the neural tube is formed dramatically increases the rate of NTDs and delays the development of chicken embryos. However, there is no sex bias with respect to NTD risk.