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Amniotic fluid testosterone: relationship with cortisol and gestational age
P Sarkar1, K Bergman, N M Fisk
1Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK. pampasarkar@aol.com
Insights
Prenatal testosterone exposure, measured in amniotic fluid, is higher in male fetuses and correlates with cortisol levels. Amniotic fluid testosterone did not change with gestational age in the second and third trimesters.
Area of Science:
- Reproductive endocrinology
- Developmental biology
- Prenatal programming
Background:
- Prenatal testosterone exposure influences future reproductive and non-reproductive behaviors.
- Prenatal stress outcomes may overlap with testosterone exposure effects.
- Amniotic fluid serves as a biomarker for fetal exposure, particularly when fetal blood sampling is infrequent.
Purpose of the Study:
- To investigate the relationship between amniotic fluid testosterone and cortisol levels.
- To examine the influence of fetal gender on these hormone levels.
- To assess the correlation with gestational age during the second and third trimesters.
Main Methods:
- Collected paired amniotic fluid and maternal plasma samples from 264 pregnant women (15-37 weeks gestation).
- Measured total testosterone and cortisol in amniotic fluid via radioimmunoassay.
- Assessed maternal plasma testosterone levels concurrently.
Main Results:
- Male fetuses exhibited significantly higher amniotic fluid testosterone levels than female fetuses.
- No significant relationship was found between amniotic fluid testosterone and gestational age in either sex.
- Amniotic fluid testosterone showed a positive correlation with amniotic fluid cortisol in both male and female fetuses.
Conclusions:
- Amniotic fluid testosterone levels remained stable throughout the second and third trimesters, challenging theories of an early fetal testosterone peak.
- The positive correlation between amniotic fluid cortisol and testosterone suggests a potential co-exposure or linked mechanism.
- These findings highlight the complex interplay of hormones during fetal development and their potential long-term programming effects.
Introduction:
Foetal exposure to testosterone is increasingly implicated in the programming of future reproductive and non-reproductive behaviour. Some outcomes associated with prenatal exposure to testosterone may be predicted from exposure to prenatal stress, suggesting a link between them. The peak serum levels of testosterone in the foetus are thought to be around 14-18 weeks' gestation, and we explored testosterone levels at different gestations. Although best investigated in foetal plasma, this is now difficult because of the decline in frequency of foetal blood sampling; in this study, we used amniotic fluid as a biomarker to investigate foetal exposure.
Aims:
To investigate the relationship between amniotic fluid testosterone, amniotic fluid cortisol, foetal gender, and gestational age.
Methods:
Paired amniotic fluid and maternal plasma samples were collected from 264 pregnant women undergoing amniocentesis between 15 and 37 weeks' gestation (median 17 weeks [119 days]). Total testosterone and cortisol in amniotic fluid, and total plasma testosterone (maternal) were measured by radioimmunoassay.
Results:
Amniotic fluid testosterone levels were higher in male than in female foetuses, with a median (interquartile range) of 0.85 nmol/l (0.60-1.17 nmol/l) and 0.28 nmol/l (0.175-0.45 nmol/l), respectively. No relationship between amniotic fluid testosterone and gestational age was detected in either sex. Amniotic fluid testosterone correlated positively with amniotic fluid cortisol in both sexes (r = 0.30 male foetuses, r = 0.33 female foetuses, P < 0.001 for both), and remained significant in multivariate analysis.
Conclusion:
Testosterone in amniotic fluid did not change with gestation in the second and third trimester, raising questions about the timing of the reported early peak in the male foetus. The positive correlation between cortisol and testosterone in amniotic fluid suggests that increased foetal exposure to cortisol may also be associated with increased exposure to testosterone.
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