o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague-Dawley rats

- o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats.
- o,p′-DDT and EE have different kinetics in uterine wet weight induction.
- o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice.
- 1256 genes were differentially expressed by both ligands in both species.
- Only 51 genes had species-specific uterine expression.

1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague-Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy.