Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure.
Level 5 - mechanism / opinion, no new human data
Animal research investigating in utero exposure effects in rats.
PubMed 17462840 · doi:10.1016/j.toxlet.2007.03.004
What was done
Pregnant Sprague-Dawley (SD) and Wistar rats were exposed in utero to di(2-ethylhexyl) phthalate (DEHP) at 750 mg/kg/day during gestational days 14 to 18 (the window of sexual differentiation). Researchers evaluated male offspring for reproductive tract malformations (epididymal agenesis and gubernacular lesions) and assessed fetal testosterone (T) levels, insulin-like peptide 3 (insl3) mRNA expression, and the insl3-to-T ratio to examine differences in fetal Leydig cell response between strains.
What was found
In utero DEHP exposure resulted in starkly different lesion profiles between strains: - Epididymal lesions occurred in 67% of SD male offspring compared to 8% of Wistar male offspring. - Gubernacular lesions occurred in 64% of Wistar male offspring compared to 0% of SD male offspring. - Fetal SD males exhibited higher insl3 mRNA expression and lower testosterone levels relative to Wistar males. - The ratio of insl3 mRNA to testosterone differed between treated SD and Wistar fetuses, indicating greater disruption of the steroidogenic pathway in the SD strain.
Why it matters
The study demonstrates that genetic background significantly alters the phenotypic manifestation of phthalate syndrome in animal models, likely through strain-specific differences in fetal Leydig cell function and vulnerability.
Limits
The study was conducted in rodents using a high exposure dose (750 mg/kg/day), limiting direct translation to human risk. The abstract does not report the total number of litters or offspring evaluated, nor does it provide exact quantitative values or confidence intervals for testosterone and insl3 mRNA measurements. Long-term adult functional outcomes were not reported in the abstract.
Cited by
- supports National Toxicology Program studies showed that prenatal exposure to phthalates causes male rodent offspring to develop less male-typical genital tracts, known as 'the phthalate syndrome.'