Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.
Front Endocrinol (Lausanne). 2022 Jun 9;13:892342. doi: 10.3389/fendo.2022.892342. eCollection 2022.
An system to study testicular maturation in rats, an important model organism for reproductive toxicity, could serve as a platform for high-throughput drug and toxicity screening in a tissue specific context. maturation of somatic cells and spermatogonia in organ culture systems has been reported. However, this has been a challenge for organoids derived from dissociated testicular cells. Here, we report generation and maintenance of rat testicular organoids in microwell culture for 28 days. We find that rat organoids can be maintained only at lower than ambient O tension of 15% and organoids cultured at 34°C have higher somatic cell maturation and spermatogonial differentiation potential compared to cultures in 37°C. Upon exposure to known toxicants, phthalic acid mono-2-ethylhexyl ester and cadmium chloride, the organoids displayed loss of tight-junction protein Claudin 11 and altered transcription levels of somatic cell markers that are consistent with previous reports in animal models. Therefore, the microwell-derived rat testicular organoids described here can serve as a novel platform for the study of testicular cell maturation and reproductive toxicity .
一种研究大鼠睾丸成熟的系统，作为生殖毒性的重要模式生物，可以作为在组织特异性背景下进行高通量药物和毒性筛选的平台。已经有报道称体细胞和精原细胞在器官培养系统中的成熟。然而，这对于从分离的睾丸细胞衍生的类器官来说是一个挑战。在这里，我们报告了在微井培养中维持大鼠睾丸类器官 28 天的方法。我们发现，只有在低于 15%的环境氧张力下，大鼠类器官才能维持生长，并且在 34°C 下培养的类器官具有更高的体细胞成熟和精原细胞分化潜力，而在 37°C 下培养的类器官则没有。在暴露于已知的有毒物质邻苯二甲酸单-2-乙基己酯和氯化镉后，类器官显示出紧密连接蛋白 Claudin 11 的丢失，以及体细胞标志物转录水平的改变，这与动物模型中的先前报道一致。因此，这里描述的微井衍生的大鼠睾丸类器官可以作为研究睾丸细胞成熟和生殖毒性的新平台。
