Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-03T11:34:58.677Z Has data issue: false hasContentIssue false
  • English
  • Français

Testosterone measured from amniotic fluid and maternal plasma shows no significant association with directional asymmetry in newborn digit ratio (2D:4D)

Published online by Cambridge University Press:  31 October 2018

G. Richards Open the ORCID record for G. Richards [Opens in a new window] ,
M. Gomes  and
T. Ventura
G. Richards*
Affiliation:
Centre for Research on Play in Education, Development & Learning, Faculty of Education, University of Cambridge, Cambridge, UK Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK
M. Gomes
Affiliation:
Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon, Portugal
T. Ventura
Affiliation:
Hospital Centre of Central Lisbon EPE, Rua Viriato, NOVA Medical School|Faculdade de Ciências Médicas, Campo Mártires da Pátria, Lisbon, Portugal
*
Address for correspondence: G. Richards, School of Psychology, Newcastle University, Ridley Building 1, Queen Victoria Road, Newcastle upon Tyne, NE1 7RU, UK. E-mail: gareth.richards@ncl.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Foetal sex hormones can have powerful and far-reaching effects on later phenotype. However, obtaining accurate measurements is difficult for ethical reasons, and researchers often employ proxy variables to examine their effects. The relative length of the second and fourth fingers (digit ratio or 2D:4D) is frequently used for this purpose, as it is hypothesized to index variance in prenatal androgen and oestrogen exposure. Most studies employing this method examine digit ratio for the right hand (R2D:4D) and/or left hand (L2D:4D), though the mean value (M2D:4D) (i.e., the average of R2D:4D and L2D:4D) and directional asymmetry (D[R–L]) (i.e., R2D:4D minus L2D:4D) are also commonly used. As no published studies have examined M2D:4D or D[R-L] in relation to testosterone measured from amniotic fluid, we conducted a secondary analysis of data published by Ventura et al. The sample comprises 106 mothers from Portugal who underwent amniocentesis during the second trimester and their neonates. Newborn M2D:4D was negatively correlated with amniotic testosterone in females (P<0.05) but not in males; no significant association was observed between amniotic testosterone and D[R–L] in either sex. In addition, we examined testosterone measured from maternal circulation during the second trimester, and found that it was not a significant predictor of M2D:4D or D[R–L] in male or female infants. Further research should aim to measure the ratio of testosterone to oestradiol present in amniotic fluid and maternal plasma, to examine whether either is a predictor of digit ratio variables at different stages of postnatal development.

Keywords

amniocentesisasymmetry2D:4Ddigit ratiotestosterone
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 3 , June 2019 , pp. 362 - 367
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Manning, JT, Scutt, D, Wilson, J, Lewis-Jones, DI. The ratio of 2nd to 4th digit length: a predictor of sperm numbers and levels of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 1998; 13, 3000–3004.CrossRefGoogle Scholar
2. Wilson, GD. Finger-length as an index of assertiveness in women. Pers Ind Diff. 1983; 4, 111–112.CrossRefGoogle Scholar
3. Manning, JT. Digit Ratio: A Pointer to Fertility, Behavior, and Health. 2002. Rutgers University Press: New Brunswick, NJ.Google Scholar
4. Manning, JT. The Finger Ratio. 2008. Faber & Faber: London, UK.Google Scholar
5. Manning, JT, Bundred, PE. The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 2000; 54, 855–857.CrossRefGoogle ScholarPubMed
6. Hönekopp, J, Watson, S. Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand. Am J Hum Biol. 2010; 22, 619–630.CrossRefGoogle ScholarPubMed
7. Austin, EJ, Manning, JT, McInroy, K, Mathews, E. A preliminary investigation of the associations between personality, cognitive ability and digit ratio. Pers Ind Diff. 2002; 33, 1115–1124.CrossRefGoogle Scholar
8. Voracek, M. Who wants to believe? Associations between digit ratio (2D:4D) and paranormal and superstitious beliefs. Pers Ind Diff. 2009; 47, 105–109.CrossRefGoogle Scholar
9. Saino, N, Rubolini, D, Romano, M, Boncoraglio, G. Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus). Naturwissenschaften. 2007; 94, 207–212.CrossRefGoogle Scholar
10. Talarovičová, A, Kršková, L, Blažeková, J. Testosterone enhancement during pregnancy influences the 2D:4D ratio and open field motor activity of rat siblings in adulthood. Horm Behav. 2009; 55, 235–239.CrossRefGoogle ScholarPubMed
11. Zheng, Z, Cohn, MJ. Developmental basis of sexually dimorphic digit ratios. Proc Natl Acad Sci U S A. 2011; 108, 16289–16294.CrossRefGoogle ScholarPubMed
12. Brown, WM, Hines, M, Fane, BA, Breedlove, SM. Masculinized finger length patterns in human males and females with congenital adrenal hyperplasia. Horm Behav. 2002; 42, 380–386.CrossRefGoogle ScholarPubMed
13. Ciumas, C, Lindén Hirschberg, A, Savic, I. High fetal testosterone and sexually dimorphic cerebral networks in females. Cereb Cortex. 2008; 19, 1167–1174.CrossRefGoogle ScholarPubMed
14. Ökten, A, Kalyoncu, M, Yariş, N. The ratio of second- and fourth-digit lengths and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Early Hum Dev. 2002; 70, 47–54.CrossRefGoogle ScholarPubMed
15. Rivas, MP, Moreira, LMA, Santo, LDE, et al. New studies of second and fourth digit ratio as a morphogenetic trait in subjects with congenital adrenal hyperplasia. Am J Hum Biol. 2014; 26, 559–561.CrossRefGoogle ScholarPubMed
16. Buck, JJ, Williams, RM, Hughes, IA, Acerini, CL. In-utero androgen exposure and 2nd to 4th digit length ratio – comparisons between healthy controls and females with classical congenital adrenal hyperplasia. Hum Reprod. 2003; 18, 976–979.CrossRefGoogle ScholarPubMed
17. Berenbaum, SA, Korman Bryk, K, Nowak, N, Quigley, CA, Moffat, S. Fingers as a marker of prenatal androgen exposure. Endocrinology. 2009; 150, 5119–5124.CrossRefGoogle ScholarPubMed
18. van Hemmen, J, Cohen-Kettenis, PT, Steensma, TD, Veltman, DJ, Bakker, J. Do sex differences in CEOAEs and 2D:4D ratios reflect androgen exposure? A study in women with complete androgen insensitivity syndrome. Biol Sex Diff. 2017; 8, 11.CrossRefGoogle ScholarPubMed
19. Manning, JT, Kilduff, LP, Trivers, R. Digit ratio (2D:4D) in Klinefelter’s syndrome. Andrology. 2013; 1, 94–99.CrossRefGoogle Scholar
20. Baron-Cohen, S, Auyeung, B, Nørgaard-Pedersen, B, et al. Elevated fetal steroidogenic activity in autism. Mol Psychiatry. 2015; 20, 369–376.CrossRefGoogle ScholarPubMed
21. Baron-Cohen, S, Lutchmaya, S, Knickmeyer, R. Prenatal Testosterone in Mind. 2004. MIT Press: Cambridge, MA.CrossRefGoogle Scholar
22. Hönekopp, J. Digit ratio 2D:4D in relation to autism spectrum disorders, empathizing, and systemizing: a quantitative review. Autism Res. 2012; 5, 221–230.CrossRefGoogle ScholarPubMed
23. Manning, JT, Baron-Cohen, S, Wheelwright, S, Sanders, G. The 2nd to 4th digit ratio and autism. Dev Med Child Neurol. 2001; 43, 160–164.CrossRefGoogle ScholarPubMed
24. Milne, E, White, S, Campbell, R, et al. Motion and form coherence detection in autistic spectrum disorder: relationship to motor control and 2:4 digit ratio. J Autism Dev Disord. 2006; 36, 225–237.CrossRefGoogle ScholarPubMed
25. Teatero, ML, Netley, C. A critical review of the research on the extreme male brain theory and digit ratio (2D:4D). J Autism Dev Disord. 2013; 43, 2664–2676.CrossRefGoogle Scholar
26. Voracek, M. Digit ratio (2D:4D) as a marker for mental disorders: low (masculinized) 2D:4D in autism-spectrum disorders, high (feminized) 2D:4D in schizophrenic-spectrum disorders. Behav Brain Sci. 2008; 31, 283–284.CrossRefGoogle Scholar
27. Schieve, LA, Tian, L, Dowling, N, et al. Associations between the 2nd to 4th digit ratio and autism spectrum disorder in population-based samples of boys and girls: findings from the Study to Explore Early Development. J Autism Dev Disord. 2018; 48, 2379–2395.CrossRefGoogle ScholarPubMed
28. Richards, G. What is the evidence for a link between digit ratio (2D:4D) and direct measures of prenatal sex hormones? Early Hum Dev. 2017; 113, 71–72.CrossRefGoogle ScholarPubMed
29. Hickey, M, Doherty, DA, Hart, R, et al. Maternal and umbilical cord androgen concentrations do not predict digit ratio (2D:4D) in girls: a prospective cohort study. Psychoneuroendocrinology. 2010; 35, 1235–1244.CrossRefGoogle Scholar
30. Mitsui, T, Araki, A, Goudarzi, H, et al. Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children. PLoS One. 2015; 10, e0120636.CrossRefGoogle ScholarPubMed
31. Mitsui, T, Araki, A, Goudarzi, H, et al. Effects of adrenal androgens during the prenatal period on the second to fourth digit ratio in school-aged children. Steroids. 2016; 113, 46–51.CrossRefGoogle ScholarPubMed
32. Manning, JT, Kilduff, L, Cook, C, Crewther, B, Fink, B. Digit ratio (2D:4D): a biomarker for prenatal sex steroids and adult sex steroids in challenge situations. Front Endocrinol. 2014; 5, 9.Google ScholarPubMed
33. Hollier, LP, Keelan, JA, Jamnadass, ESL, et al. Adult digit ratio (2D:4D) is not related to umbilical cord androgen or estrogen concentrations, their ratios or net bioactivity. Early Hum Dev. 2015; 91, 111–117.CrossRefGoogle ScholarPubMed
34. Cohen-Bendahan, CCC, van de Beek, C, Berenbaum, SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev. 2005; 29, 353–384.CrossRefGoogle ScholarPubMed
35. Hollier, LP, Keelan, JA, Hickey, M, Maybery, MT, Whitehouse, AJO. Measurement of androgen and estrogen concentrations in cord blood: accuracy, biological interpretation, and applications to understanding human behavioral development. Front Endocrinol. 2014; 5, 64.CrossRefGoogle ScholarPubMed
36. Hines, M. Brain Gender. 2004. Oxford University Press: New York, NY.Google Scholar
37. van de Beek, C, Thijssen, JHH, Cohen-Kettenis, PT, van Goozen, SHM, Buitelaar, JK. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure? Horm Behav. 2004; 46, 663–669.CrossRefGoogle ScholarPubMed
38. Lutchmaya, S, Baron-Cohen, S, Raggatt, P, Knickmeyer, R, Manning, JT. 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Hum Dev. 2004; 77, 23–28.CrossRefGoogle ScholarPubMed
39. Ventura, T, Gomes, MC, Pita, A, Neto, MT, Taylor, A. Digit ratio (2D:4D) in newborns: influences of prenatal testosterone and maternal environment. Early Hum Dev. 2013; 89, 107–112.CrossRefGoogle ScholarPubMed
40. Manning, JT, Fink, B. Are there any “direct” human studies of digit ratio (2D:4D) and measures of prenatal sex hormones? Early Hum Dev. 2017; 113, 73–74.CrossRefGoogle ScholarPubMed
41. Barona, M, Kothari, R, Skuse, D, Micali, N. Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample. Mol Autism. 2015; 6, 68.CrossRefGoogle Scholar
42. Ventura, T, Gomes, MC, Carreira, T. Cortisol and anxiety response to a relaxing intervention on pregnant women awaiting amniocentesis. Psychoneuroendocrinology. 2012; 37, 148–156.CrossRefGoogle ScholarPubMed
43. Kulle, AE, Riepe, FG, Melchior, D, Hiort, O, Holterhus, PM. A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone, and dihydrotestosterone in pediatric blood samples: age- and sex-specific reference data. J Clin Endocrinol Metab. 2010; 95, 2399–2409.CrossRefGoogle ScholarPubMed
44. Manning, JT. Resolving the role of prenatal sex steroids in the development of digit ratio. Proc Natl Acad Sci U S A. 2011; 108, 16143–16144.CrossRefGoogle ScholarPubMed
45. Knickmeyer, RC, Woolson, S, Hamer, RM, Konneker, T, Gilmore, JH. 2D:4D ratios in the first 2 years of life: stability and relation to testosterone exposure and sensitivity. Horm Behav. 2011; 60, 256–263.CrossRefGoogle ScholarPubMed
46. Richards, G, Bellin, W, Davies, W. Familial digit ratio (2D:4D): associations in a general population sample from Wales. Early Hum Dev. 2017; 112, 14–19.CrossRefGoogle Scholar
47. Trivers, RL, Manning, JT, Jacobson, A. A longitudinal study of digit ratio (2D:4D) and other finger ratios in Jamaican children. Horm Behav. 2006; 49, 150–156.CrossRefGoogle ScholarPubMed
48. Faul, F, Erdfelder, E, Buchner, A, Lang, A-G. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009; 41, 1149–1160.CrossRefGoogle ScholarPubMed
49. Faul, F, Erdfelder, E, Lang, A-G, Buchner, A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007; 39, 175–191.CrossRefGoogle ScholarPubMed
50. Rodeck, CH, Gill, D, Rosenberg, DA, Collins, WP. Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid. Prenat Diagn. 1985; 5, 175–181.CrossRefGoogle ScholarPubMed
51. Manning, JT, Fink, B, Neave, N, Caswell, N. Photocopies yield lower digit ratios (2D:4D) than direct finger measurements. Arch Sex Behav. 2005; 34, 329–333.CrossRefGoogle ScholarPubMed
52. Ribeiro, E, Neave, N, Morais, RN, Manning, JT. Direct versus indirect measurement of digit ratio (2D:4D): a critical review of the literature and new data. Evol Psychol. 2016; 14, 1–8.CrossRefGoogle Scholar