Toxicological Sciences
Toxicological Sciences
5 years ago

Differential Effects of Exposure to Single versus a Mixture of Endocrine-Disrupting Chemicals on Steroidogenesis Pathway in Mouse Testes.

Moreno, Castañeda-Zegarra, Cruz-Fernandes, Del Mazo, Larriba, Rodriguez-Fernandez, Buñay, Patiño-Garcia
Endocrine-disrupting chemicals (EDCs) generate reproductive dysfunctions affecting the biosynthesis of steroid hormones and genes of the steroidogenic pathway. EDCs effects are mainly reported as a result of exposure to single compounds. However, humans are environmentally exposed to a mixture of EDCs. Herein, we assess chronic exposure to single alkylphenols and phthalates versus a mixture in mouse testes histology and steroidogenesis. Pregnant mice were exposed through drinking water to: 0.3 mg/Kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP), 0.05 mg/Kg-BW/day of each alkylphenol (NP, OP), or their mixture, covering from 0.5 post-coital day to weaning, continuing in the male offspring each exposure until adulthood (60 days old). Body and relative testis weight were increased in mixture-exposed mice along with histological alterations. Intratesticular testosterone (T) changed only in mice exposed to DBP, whereas estradiol (E2) levels were altered in all groups (except BBP). mRNA levels of genes encoding hormones of the steroid pathway (Cyp11a1, Hsd3b1, Cyp17a1 and Cyp19a1), cholesterol transporters (Star), and transcriptional factors (Sp1) showed that mice exposed to single or mixed compounds had alterations in at least two transcripts. However, none of the different types of exposure induced changes in all transcripts. In addition, changes at the mRNA or protein levels with single compounds were not always the same as those with a mixture. In conclusion, the effects of a chronic exposure to a mixture of EDCs on the expression of genes and proteins of the steroidogenic pathway and hormonal status were different from those exposed to single EDC.

Publisher URL: http://doi.org/10.1093/toxsci/kfx200

DOI: 10.1093/toxsci/kfx200

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