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Prenatal Stress as a Modifier of Associations between Phthalate Exposure and Reproductive Development: results from a
Emily S Barrett1, Lauren E Parlett2, Sheela Sathyanarayana3,4
1Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Insights
Prenatal phthalate exposure was linked to shorter anogenital distance (AGD) in infant males, but only when mothers experienced no prenatal stress. This suggests prenatal stress may alter how phthalates affect male genital development.
Area of Science:
- Environmental health
- Reproductive toxicology
- Developmental biology
Background:
- Prenatal exposure to phthalates, such as diethylhexyl phthalate (DEHP), is linked to adverse male reproductive tract development, including reduced anogenital distance (AGD).
- Anogenital distance (AGD) serves as a key indicator of prenatal androgen exposure and may be influenced by maternal stress during pregnancy.
- The interactive effects of prenatal phthalate exposure and maternal stress on infant AGD remain largely unexplored.
Purpose of the Study:
- To investigate whether prenatal exposure to stressful life events (SLEs) modifies the association between prenatal phthalate exposure and infant anogenital distance (AGD).
Main Methods:
- Urine samples from 738 pregnant women in the first trimester were analyzed for phthalate metabolites, including diethylhexyl phthalate (DEHP) and its sum (ΣDEHP).
- Maternal reports of stressful life events (SLEs) during pregnancy were collected, categorizing women into 'lower' (0 SLEs) and 'higher' (1+ SLEs) stress groups.
- Adjusted multiple regression models were used to assess the relationship between phthalate concentrations and infant AGD, stratified by infant sex and maternal stress level.
Main Results:
- In male infants of mothers in the lower stress group, higher first-trimester ΣDEHP concentrations were inversely associated with both anoscrotal distance (AGD-AS) and anopenile distance (AGD-AP).
- Conversely, in male infants of mothers in the higher stress group, the associations between ΣDEHP and AGD measures were predominantly positive and not statistically significant.
- No significant associations between prenatal phthalate metabolites and AGD were observed in female infants.
Conclusions:
- The observed inverse association between prenatal phthalate exposure and male genital development (AGD) was evident only in infants born to mothers reporting no prenatal stressful life events.
- These findings indicate a potential interaction between prenatal phthalate exposure and maternal stress, which may collectively influence fetal development of the male reproductive tract.
- Further research is warranted to elucidate the complex interplay between environmental exposures and stress during gestation on reproductive health outcomes.
Background:
Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs).
Methods:
Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress group) using adjusted multiple regression interaction models.
Results:
In the lower stress group, first trimester ΣDEHP was inversely associated with two measures of male AGD: anoscrotal distance (AGD-AS; β = -1.78; 95% CI -2.97, -0.59) and anopenile distance (AGD-AP; β = -1.61; 95% CI -3.01, -0.22). By contrast, associations in the higher stress group were mostly positive and non-significant in male infants. No associations were observed in girls.
Conclusions:
Associations between prenatal phthalate exposure and altered genital development were only apparent in sons of mothers who reported no SLEs during pregnancy. Prenatal stress and phthalates may interact to shape fetal development in ways that have not been previously explored.
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