Thyroid hormone receptor gene expression in first trimester human fetal brain

Area of Science:

• Developmental biology
• Neuroendocrinology
• Molecular biology

Background:

• Maternal thyroid hormone is vital for fetal brain development.
• Thyroid hormone nuclear receptor (TR) proteins are present in the fetal brain.
• The specific TR isoforms and their developmental roles in early human pregnancy are not fully understood.

Purpose of the Study:

• To investigate the ontogeny of TR isoforms and splice variants in the first trimester human fetal brain.
• To determine the expression patterns of TR isoforms during early human development.

Main Methods:

• Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was used.
• Human fetal brain samples from the first trimester (n=9) were analyzed.
• Expression levels of TRbeta1, TRalpha1, c-erbAalpha2, and c-erbAalpha3 variants were quantified.

Main Results:

• TRbeta1, TRalpha1, and c-erbAalpha2 isoforms were detected from 8.1 weeks gestation.
• A splice variant, c-erbAalpha3, was also identified.
• TRalpha-derived transcripts showed coordinate expression and an 8-fold increase between 8.1 and 13.9 weeks gestation.
• TRbeta1 exhibited a more complex expression pattern with a potential nadir between 8.4 and 12.0 weeks gestation.

Conclusions:

• The TRalpha1 isoform plays a significant role in mediating maternal thyroid hormone action during first trimester human fetal brain development.
• Specific TR isoforms show distinct temporal expression patterns during early human neurodevelopment.