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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Early-life phthalate mixture exposure and reproductive hormone levels during minipuberty
Viola Trevisani1,2, Laura Lucaccioni2, Federico Starace3
1PhD program in Clinical and Experimental Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Insights
Early exposure to phthalates (PAEs) alters infant reproductive hormones during minipuberty. This study found PAE mixtures significantly impact urinary hormone levels in a sex-specific manner, highlighting a critical window for endocrine disruption.
Area of Science:
- Environmental Health
- Endocrinology
- Pediatrics
Background:
- Phthalates (PAEs) are widespread endocrine-disrupting chemicals (EDCs) with known prenatal effects.
- The impact of PAEs during early postnatal life, particularly during minipuberty (infant HPG axis activation), is less understood.
- Minipuberty is a crucial period for endocrine programming.
Purpose of the Study:
- To investigate the association between early-life exposure to PAEs and urinary reproductive hormone levels in infants during minipuberty.
- To assess sex-specific effects of PAE exposure on the hypothalamic-pituitary-gonadal (HPG) axis.
- To evaluate the impact of PAE mixtures on hormonal profiles.
Main Methods:
- Longitudinal study of infants from the Modena birth cohort with urine sampling at birth, 3, and 6 months.
- Measurement of urinary PAE metabolites and reproductive hormones (uLH, uFSH, uT, uE).
- Statistical analysis using Spearman correlations, linear regression, and mixture models (WQS regression, quantile g-computation).
Main Results:
- PAE metabolites were detected in nearly all infant urine samples, indicating widespread exposure.
- Positive associations were observed between PAE exposure and urinary hormone levels in a sex-specific manner.
- In males, PAEs were linked to increased uFSH and uT; in females, associations with uFSH and uE were noted at later timepoints.
- Mixture analyses identified MnBP, MBzP, and ΣDEHPm as key contributors, with results consistent across different analytical methods.
Conclusions:
- Early-life exposure to PAE mixtures is associated with sex-specific alterations in reproductive hormone levels during infant minipuberty.
- Minipuberty represents a sensitive developmental window for endocrine disruption by PAEs.
- Further research is needed to understand the long-term implications of these early hormonal changes for reproductive health.
Background:
Phthalates (PAEs) are ubiquitous endocrine-disrupting chemicals (EDCs) with well-documented prenatal effects, while their impact during early postnatal life remains less understood. Minipuberty, a transient activation of the hypothalamic-pituitary-gonadal (HPG) axis in early infancy, represents a critical window of endocrine programming. This study aimed to investigate the association between early-life exposure to PAEs and urinary reproductive hormone levels during minipuberty in healthy term-born infants.
Methods:
This longitudinal study included infants from the Modena birth cohort with repeated urine sampling at birth (T0), 3 (T3), and 6 months (T6). Urinary concentrations of PAE metabolites (MMP, MEP, MnBP, MBzP, ΣDEHPm) and urine reproductive hormones (uLH, uFSH, uT and uE) were measured. Associations were assessed using sex-stratified Spearman correlations, single-pollutant linear regression models, and mixture approaches, including Weighted Quantile Sum (WQS) regression and quantile g-computation (qgcomp).
Results:
PAE metabolites were evaluated in 162 infants and detected in nearly all samples, confirming widespread exposure. Consistent positive associations emerged between PAE exposure and urinary hormone levels. In males, increasing levels of metabolites were significantly associated particularly with increased uFSH and uT, at all timepoints. In females, associations were more evident at T3 and T6, mainly involving uFSH and uE. Mixture analyses confirmed these findings and identified MnBP, MBzP, and ΣDEHPm as the main contributors. Results were consistent across methods, highlighting a mixture association beside an isolated compound-specific findings.
Conclusion:
Early-life exposure to PAE mixtures is associated with sex-specific alterations in reproductive hormone levels during minipuberty. These findings highlight minipuberty as a sensitive window for endocrine disruption and underscore the importance of considering chemical mixtures in environmental health research. However, further studies are needed to determine whether these early hormonal perturbations may have implications for long-term reproductive development and health.
