NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden.
Division of Neurogeriatrics, Department of Neurobiology Care Sciences & Society, Karolinska Institutet, 141 83 Huddinge, Sweden.
Cells. 2021 Jan 27;10(2):241. doi: 10.3390/cells10020241.
Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
对于尚未能够产生成熟精子的男性儿童癌症幸存者,生育力保存依赖于实验方法,如睾丸组织体外培养。尽管在人类睾丸组织体外培养中可以观察到体细胞成熟的最初步骤,但生殖细胞耗竭是一个常见的障碍。因此,了解精原干细胞(SSC)的生态位环境,特别是特定的成分,如曲细精管基底膜(BM),将有助于睾丸组织体外培养的进展。在这里,我们揭示了曲细精管 BM 从受孕后 6 周开始形成,表达层粘连蛋白α 1(LAMA1)和 IV 型胶原,这些成分在整个发育过程中作为关键成分持续存在。在青春期前的睾丸组织体外培养中,我们发现曲细精管 LAMA1 的表达随着培养时间的延长而被破坏和耗竭,与生殖细胞的丢失相关。这些发现强调了 LAMA1 对于人类 SSC 生态位的重要性及其对培养条件的敏感性。