Description
- Abstract:
- Exposure to excess retinoic acid (RA) disrupts the development of the mammalian testicular seminiferous cord. However, the molecular events surrounding RA-driven loss of cord structure have not previously been examined. To investigate the mechanisms associated with this adverse developmental effect, fetal rat testes were isolated on gestational day 15, after testis determination and the initiation of cord development, and cultured in media containing all-trans RA (ATRA; 10−8 to 10−6 M) or vehicle for 3 days. ATRA exposure resulted in a concentration-dependent decrease in the number of seminiferous cords per testis section and number of germ cells, assessed by histopathology and immunohistochemistry. Following 1 day of culture, genome-wide expression profiling by microarray demonstrated that ATRA exposure altered biological processes related to retinoid metabolism and gonadal sex determination. Real-time RT-PCR analysis confirmed that ATRA enhanced the expression of the key ovarian development gene Wnt4 and the antitestis gene Nr0b1 in a concentration-dependent manner. After 3 days of culture, ATRA-treated testes contained both immunohistochemically DMRT1-positive and FOXL2-positive somatic cells, providing evidence of disrupted testicular cell fate maintenance following ATRA exposure. We conclude that exogenous RA disrupts seminiferous cord development in ex vivo cultured fetal rat testes, resulting in a reduction in seminiferous cord number, and interferes with maintenance of somatic cell fate by enhancing expression of factors that promote ovarian development.
- Notes:
- This research is supported by the National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program P42ES013660
Access Conditions
- Use and Reproduction
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- Attribution 4.0 International (CC BY 4.0)
Citation
Spade, Daniel J., Dere, Edward, Hall, Susan J., et al.,
"Supplementary data from 'All-Trans Retinoic Acid Disrupts Development in Ex Vivo Cultured Fetal Rat Testes. I: Altered Seminiferous Cord Maturation and Testicular Cell Fate'"
(2018).
Brown Superfund Data Products, Brown University Open Data Collection, Brown Superfund Project 1: Molecular Biomarkers for Assessing Testicular Toxicity Digital Archive.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:947808/
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Brown Superfund Data Products
This collection contains data sets, code, and documentation files associated with the Brown University Superfund Research Program's investigators and research projects.... -
Brown University Open Data Collection
This collection contains open and public access data sets created by Brown University faculty and student researchers. Increasingly, publishers and funders are requiring that protocols, data sets, documentation and code underlying publications be retained and preserved in repositories, their locations …... -
Brown Superfund Project 1: Molecular Biomarkers for Assessing Testicular Toxicity Digital Archive
This archive is for the long-term preservation and public dissemination of data and digital research products collected and created by researchers associated with Brown University Superfund Research Program Project 1: "Molecular Biomarkers for Assessing Testicular Toxicity". Project Leader: Kim Boekelheide, …...