Poster Presentation ESA-SRB Conference 2015

Differential maternal and paternal genome effects on circulating thyroid hormone concentrations and deiodinase expression in the midgestation fetus (#278)

Consuelo Estrella 1 2 , Karen L. Kind 1 3 , Greg S. Nattrass 4 , David J. Kennaway 1 5 , Stefan G. Hiendleder 1 2
  1. Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia
  2. JS Davies Epigenetics and Genetics Group, School ofAnimal and Veterinary Sciences, The Univeristy of Adelaide, Roseworthy, South Australia, Australia
  3. School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia
  4. Livestock and Farming Systems, South Australian Research and Development Institute, Roseworthy, South Australia, Australia
  5. Medical School, The University of Adelaide, Adelaide, South Australia, Australia

Deiodinases in placental and fetal tissues regulate the bioavailability of thyroid hormones and thus play an essential role in fetal growth.  Non-equivalence of maternal and paternal genomes, i.e., genomic imprinting, has been demonstrated in the thyroid axis1. Deiodinase 3 (DIO3) is expressed from the paternal allele only and converts thyroxine (T4) to reverse triiodothyronine (rT3), preventing overexposure of fetal tissues to triiodothyronine (T3).  DIO1 and DIO2 on the other hand, convert T4 to T3.  Genomic imprinting and other epigenetic mechanisms that lead to allelic imbalance can impact on estimated effects of genetic markers involved in thyroid hormone regulation.  Parental genome effects on fetal thyroid hormone levels and deiodinase expression have not been studied.  We have previously demonstrated that a bovine model with Bos taurus taurus and Bos taurus indicus genetics in purebred and reciprocal cross fetuses at midgestation (Day153) can dissect maternal and paternal genome effects on fundamental fetal characteristics2,3.  Here we show in the same resource (n=73) using linear models, that paternal genome affects umbilical cord plasma rT3 (P<0.001) and total T4 (P<0.001) levels, while maternal genome affects cord plasma free T4 (fT4) (P<0.001). Circulating T3 and fT3 levels were below assay sensitivity. Hepatic DIO1 transcript abundance was affected by maternal genome (P<0.001) and correlated with plasma fT4 (r=0.28, P<0.05) and rT3 (r=-0.26, P<0.05).  Renal DIO3 transcript was correlated with plasma fT4 (r=0.45, P<0.001) and rT3 (r=0.29, P<0.05), but was not affected by paternal genome.  Consistent with imprinted paternal expression, placental DIO3 transcript was affected by paternal genome (P<0.05), but was not correlated with circulating hormone, suggesting it is not a major contributor of fetal rT3.  In conclusion, we have demonstrated strong differential parental genome effects on thyroid hormones and correlated these with major regulators of thyroid hormone metabolism.

  1. HERNANDEZ, A., FIERING, S., MARTINEZ, E., GALTON, V. A. & ST. GERMAIN, D. 2002. The Gene Locus Encoding Iodothyronine Deiodinase Type 3 (Dio3) Is Imprinted in the Fetus and Expresses Antisense Transcripts. Endocrinology, 143, 4483-4486.
  2. XIANG, R., GHANIPOOR-SAMAMI, M., JOHNS, W. H., EINDORF, T., RUTLEY, D. L., KRUK, Z. A., FITZSIMMONS, C. J., THOMSEN, D. A., ROBERTS, C. T., BURNS, B. M., ANDERSON, G. I., GREENWOOD, P. L. & HIENDLEDER, S. 2013. Maternal and paternal genomes differentially affect myofibre characteristics and muscle weights of bovine fetuses at midgestation. PLOS ONE, 8, e53402.
  3. XIANG, R., LEE, A. M. C., EINDORF, T., JAVADMANESH, A., GHANIPOOR-SAMAMI, M., GUGGER, M., FITZSIMMONS, C. J., KRUK, Z. A., PITCHFORD, W. S., LEVITON, A. J., THOMSEN, D. A., BECKMAN, I., ANDERSON, G. I., BURNS, B. M., RUTLEY, D. L., XIAN, C. J. & HIENDLEDER, S. 2014. Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation. Journal of Bone and Mineral Research, 29, 2392–2404