Aquat Toxicol 2020 Sep 01;226:105557. doi: 10.1016/j.aquatox.2020.105557.

Transcriptomic analysis identifies early cellular and molecular events by which estrogen disrupts testis differentiation and causes feminization in Xenopus laevis.

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Extensive studies have shown that estrogenic endocrine-disrupting chemicals (EDCs) can disrupt testis differentiation and even cause feminization in vertebrates. However, little is known about the mechanisms by which estrogenic EDCs disrupt testis differentiation. Here, we employed Xenopus laevis, a model amphibian species sensitive to estrogenic EDCs, to explore the molecular and cellular events by which 17β-estradiol (E2) disrupts testis differentiation and causes feminization. Following waterborne exposure to E2 from stage 45/46, genetically male X. laevis were confirmed to undergo testis differentiation inhibition and ovary differentiation activation at stages 52 and 53, ultimately displaying gonadal feminization at stage 66. Using a time-course RNA sequencing approach, we then identified thousands of differentially expressed transcripts (DETs) in genetically male gonad-mesonephros complexes at stages 48, 50 and 52 (the window for testis differentiation) between E2 treatment and the control. Enrichment analysis suggests alterations in cell proliferation, extracellular matrix, and cell motility following E2 exposure. Further verification by multiple methods demonstrated that E2 inhibited cell proliferation, disrupted extracellular matrix, and altered cell motility in the genetically male gonads compared with controls, implying that these events together contributed to testis differentiation disruptions and feminization in X. laevis. This study for the first time uncovered some of the early molecular and cellular events by which estrogen disrupts testicular differentiation and causes feminization in X. laevis. These new findings improve our understanding of the mechanisms by which estrogenic EDCs disrupt testicular differentiation in vertebrates.

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Species referenced: Xenopus laevis
Genes referenced: a2m acta4 actc1 amh anln arpc1a aurka c3 c5 c8b c9 ccl4 cd274 cd44 ceacam8 cfh cfi ckap2 cldn19 clu coro6 cyp19a1 dm-w dmrt1 f10 f13b f2 f5 fcn1 fga fgb fgg foxl2 itih2 kif15 kif20a kif2c masp1 masp2 myh13 myl11 mypn plg proc psmd10 rpl8 serpina1 serpinc1 sox9 synpo2 tacc3 tjp3 tpm1 umod.1 vtn zan
GO keywords: cell proliferation [+]
???displayArticle.antibodies??? Lama1 Ab1 Vtn ab1