Germ cell depletion in recipient testis has adverse effects on spermatogenesis in orthotopically transplanted testis pieces via retinoic acid insufficiency
Germ cell depletion in recipient testis has adverse effects on spermatogenesis in orthotopically transplanted testis pieces via retinoic acid insufficiency
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DOI：
10.1038/s41598-020-67595-1
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发表时间：
2020-07
影响因子：
4.6
通讯作者：
A. Tsuchimoto;Masaaki Tone;N. Ogonuki;Masashi Hada;A. Ogura;S. Takashima
中科院分区：
文献类型：
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作者：
A. Tsuchimoto;Masaaki Tone;N. Ogonuki;Masashi Hada;A. Ogura;S. Takashima
精原干细胞移植成功的关键是去除受者睾丸中的生殖细胞。然而，我们发现这种处理对原位移植的供体睾丸组织的精子发生有不利影响。在供体组织中，生殖细胞中的视黄酸（RA）8（STRA 8）表达刺激的频率降低，表明精子发生所必需的RA信号在生殖细胞耗竭的受体睾丸中减弱。在这种情况下，生殖细胞耗竭减少了睾丸Aldh 1a 2的表达，这是负责睾丸RA合成，而Cyp 26 b1，这是负责睾丸RA代谢，即使在生殖细胞耗竭后仍然表达，这表明RA合成/代谢比的改变。这些结果表明，RA不足是供体精子发生缺陷的原因之一。事实上，重复RA管理显着改善供体精子生成产生生育后代没有任何副作用。这些发现可能有助于改善男性的生育能力保护技术，特别是预防青春期前癌症患者化疗引起的医源性不孕。
Germ cell depletion in recipient testes is indispensable for successful transplantation of spermatogonial stem cells. However, we found that such treatment had an adverse effect on spermatogenesis of orthotopically transplanted donor testis tissues. In the donor tissue, the frequency of stimulated by retinoic acid (RA) 8 (STRA8) expression was reduced in germ cells, suggesting that RA signalling indispensable for spermatogenesis was attenuated in germ cell-depleted recipient testes. In this context, germ cell depletion diminished expression of testicularAldh1a2, which is responsible for testicular RA synthesis, whileCyp26b1, which is responsible for testicular RA metabolism, was still expressed even after germ cell depletion, suggesting an alteration of the RA synthesis/metabolism ratio. These observations suggested that RA insufficiency was one of the causes of the defective donor spermatogenesis. Indeed, repetitive RA administrations significantly improved donor spermatogenesis to produce fertile offspring without any side effects. These findings may contribute to improving fertility preservation techniques for males, especially to prevent iatrogenic infertility induced by chemotherapy in prepubertal cancer patients.