Vitamin A Deficiency Results in Meiotic Failure and Accumulation of Undifferentiated Spermatogonia in Prepubertal Mouse Testis
Vitamin A Deficiency Results in Meiotic Failure and Accumulation of Undifferentiated Spermatogonia in Prepubertal Mouse Testis
复制标题
DOI：
10.1095/biolreprod.110.086157
复制
发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Clagett-Dame, Margaret
中科院分区：
文献类型：
--
作者：
Li, Hui;Palczewski, Krzysztof;Clagett-Dame, Margaret
维生素A（视黄醇）是维持成年哺乳动物精子发生所必需的。在成年啮齿动物中，维生素A戒断后，生精上皮内的分化生殖细胞丢失，精子发生中断，可通过维生素A替代恢复。然而，维生素A是否在小鼠精子发生的第一轮生殖细胞的分化和减数分裂起始中起作用尚不清楚。在本研究中，我们发现，维生素A消耗显着降低睾丸表达的全反式视黄酸反应基因，Stra 8，并导致减数分裂失败，在青春期前缺乏卵磷脂：视黄醇酰基转移酶（Lrat），编码的主要酶在肝脏负责形成视黄酯。而不是经历正常的分化，生殖细胞积累在睾丸Lrat（-/-）小鼠维持维生素A缺乏的饮食。这些结果，连同我们以前的观察，生殖细胞未能进入减数分裂，并保持未分化的胚胎维生素A缺乏的卵巢，支持的假设，维生素A调节减数分裂I的卵子发生和精子发生在哺乳动物中的启动。
Vitamin A (retinol) is required for maintenance of adult mammalian spermatogenesis. In adult rodents, vitamin A withdrawal is followed by a loss of differentiated germ cells within the seminiferous epithelium and disrupted spermatogenesis that can be restored by vitamin A replacement. However, whether vitamin A plays a role in the differentiation and meiotic initiation of germ cells during the first round of mouse spermatogenesis is unknown. In the present study, we found that vitamin A depletion markedly decreased testicular expression of the all-trans retinoic acid-responsive gene, Stra8, and caused meiotic failure in prepubertal male mice lacking lecithin: retinol acyltransferase (Lrat), encoding for the major enzyme in liver responsible for the formation of retinyl esters. Rather than undergoing normal differentiation, germ cells accumulated in the testes of Lrat(-/-) mice maintained on a vitamin A-deficient diet. These results, together with our previous observations that germ cells fail to enter meiosis and remain undifferentiated in embryonic vitamin A-deficient ovaries, support the hypothesis that vitamin A regulates the initiation of meiosis I of both oogenesis and spermatogenesis in mammals.