Fertility impairment with defective spermatogenesis and steroidogenesis in male zebrafish lacking androgen receptor
Fertility impairment with defective spermatogenesis and steroidogenesis in male zebrafish lacking androgen receptor
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缺乏雄激素受体的雄性斑马鱼的生育能力受损，精子发生和类固醇生成缺陷
DOI：
10.1093/biolre/iox165
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发表时间：
2018
影响因子：
3.6
通讯作者：
Liu Xiaochun
中科院分区：
文献类型：
--
作者：
Tang Haipei;Chen Yu;Wang Le;Yin Yike;Li Gaofei;Guo Yin;Liu Yun;Lin Haoran;Cheng Christopher H. K.;Liu Xiaochun
雄激素受体（AR）在调节男性生育中的关键作用在过去的二十年中引起了广泛的研究关注。以往的研究表明，AR基因敲除会导致小鼠精子发生不完全，血清睾酮水平降低，导致无精子症和不育。然而，对于鱼体控制雄鱼生育力的确切生理作用，人们仍然知之甚少。本研究利用转录激活因子样效应子核酸酶基因构建了一个敲除斑马鱼的细胞系。在自然交配试验中，发现睾丸较小的同精突变雄鱼不育。有趣的是，在突变鱼中观察到少量的成熟精子。这些成熟精子可以与健康卵母细胞体外受精，但受精率较低。此外，睾丸中大多数类固醇基因的表达水平在突变体中显著升高。相反，突变体中雌二醇和11-酮睾酮（11-KT）水平显著降低，表明突变体中类固醇合成缺陷。此外，与野生型相比，突变体的血清LHβ蛋白水平显著降低，这可能是由于类固醇激素水平降低的正反馈。
The pivotal role of androgen receptor (AR) in regulating male fertility has attracted much research attention in the past two decades. Previous studies have shown that total AR knockout would lead to incomplete spermatogenesis and lowered serum testosterone levels in mice, resulting in azoospermia and infertility. However, the precise physiological role ofarin controlling fertility of male fish is still poorly understood. In this study, we have established anarknockout zebrafish line by transcription activator-like effectors nucleases. Homozygousarmutant male fish with smaller testis size were found to be infertile when tested by natural mating. Intriguingly, a small amount of mature spermatozoa was observed in thearmutant fish. These mature spermatozoa could fertilize healthy oocytes, albeit with a lower fertilization rate, byin vitrofertilization. Moreover, the expression levels of most steroidogenic genes in the testes were significantly elevated in thearmutants. In contrast, the levels of estradiol and 11-ketotestosterone (11-KT) were significantly decreased in thearmutants, indicating that steroidogenesis was defective in the mutants. Furthermore, the protein level of LHβ in the serum decreased markedly in thearmutants when compared with wild-type fish, probably due to the positive feedback from the diminished steroid hormone levels.