Agents within a Developmental Complex Adaptive System: Intrauterine Male Hormones Influence Human Tooth Size and Shape

Agents within a Developmental Complex Adaptive System: Intrauterine Male Hormones Influence Human Tooth Size and Shape

F. Lam R. Yong S. Ranjitkar G.C. Townsend A.H. Brook 

School of Dentistry, University of Adelaide, Australia

Institute of Dentistry, Queen Mary University of London, England

1 October 2016
| Citation



Dental development is a complex adaptive system (CAS) in which genetic, epigenetic and environmental factors interact during different developmental stages to influence final tooth size and shape. From these complex interactions, a self-regulating and self-organising system emerges with spatiotemporal, multidimensional, multilevel and multifactorial components. The aim of this study was to quantify the influence of intrauterine male hormones on the mesiodistal dimension of permanent teeth by studying females from opposite-sex (OS) and same-sex (SS) twin pairs to explore dental development as a CAS. A custom-designed 2D image analysis system was used to measure the mesiodistal dimension from the occlusal view in each permanent tooth of 30 dizygotic OS and 30 dizygotic SS female twin pairs. Linear mixed models were used to quantify the differences in tooth size and shape. The mean mesiodistal tooth dimension was greater in the OS cohort for the majority of the permanent dentition. These findings reflected the complex interactions between genetic, epigenetic and environmental factors and their outcomes during development. The results indicated the transmission of the male hormones to the female in utero influencing her endocrine system, leading to epigenetic changes and so affecting gene expression. This demonstrated prenatal sex hormones as an environmental agent influencing multiple interactions within a developmental CAS.


complex adaptive systems, dental development, epigenetic, genetic, phenomics, prenatal sex hormones, sexual dimorphism, Y chromosome


[1] Brook, A.H., The dentition: the outcomes of morphogenesis leading to variations of tooth number, size and shape. Australian Dental Journal, 59, pp. 131–142, 2014.

[2] Brook, A., Brook O’Donnell, M., Hone, A., Hart, E., Hughes, T., Smith R. & Townsend, G., General and craniofacial development are complex adaptive processes influenced by diversity. 

Australian Dental Journal, 59S, pp. 13–22, 2014.

[3] Ribeiro, D.C., Brook, A.H., Hughes, T.E., Sampson, W.J. & Townsend, G.C., Intrauterine hormone effects on tooth dimensions. Journal of Dental Research, 92, pp. 425–431, 2013.

[4] Gilbert, S.F., Chromosomal Sex Determination in Mammals. Developmental Biology, 6th edn., Sinauer Associates: Sunderland, MA, 2001.

[5] Miller, E.M., Prenatal sex hormone transfer: a reason to study opposite sex twins. Personality and Individual Differences, 17, pp. 511–529, 1994.

[6] Townsend, G. & Brook, A., Genetic, epigenetic and environmental influences on dental development. Ortho Tribune, 3, pp. 4–6, 2008.

[7] Barros, S.P. & Offenbacher, S., Epigenetics: connecting environment and genotype to phenotype and disease. Journal of Dental Research, 88, pp. 400–408, 2009.

[8] Brook, A., Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Archives of Oral Biology, 54S, pp. 

3–17, 2009.

[9] Townsend, G., Hughes, T., Bockmann, M., Smith, R. & Brook, A., How studies of twins can inform our understanding of dental morphology. Frontiers of Oral Biology, 13, pp. 136–141, 2009.

[10] Bell, J.T. & Spector, T.D., A twin approach to unraveling epigenetics. Trends in Genetics, 27, pp. 116–125, 2011.

[11] Bernal, J.E., Duran, C. & Papiha, S.S., Transcriptional and epigenetic regulation of human microRNAs. Cancer Letters, 331(1), pp. 1–10, 2012.

[12] Yong, R., Ranjitkar, S., Townsend, G.C., Smith, R.N., Evans, A.R., Hughes, T.E., Lekkas, D. & Brook, A.H., Dental phenomics: advancing genotype to phenotype correlations in craniofacial research. Australian Dental Journal, 59, pp. 34–47, 2014.

[13] Houle, D., Govindaraju, D.R. & Omholt, S., Phenomics: the next challenge. Nature Reviews Genetics, 11, pp. 855–866, 2010.