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Fertility impairment with defective spermatogenesis and steroidogenesis in male zebrafish lacking androgen receptor.

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      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 androgen receptor knockout would lead to incomplete spermatogenesis and a lowered serum testosterone levels in mice, resulting in azoospermia and infertility. However, the precise physiological role of ar in controlling fertility of male fish is still poorly understood. In this study, we have established an ar knockout zebrafish line by transcription activator-like effectors nucleases (TALENs). Homozygous ar mutant 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 the ar mutant fish. These mature spermatozoa could fertilize healthy oocytes, albeit with a lower fertilization rate, by in vitro fertilization. Moreover, the expression levels of most steroidogenic genes in the testes were significantly elevated in the ar mutants. In contrast, the levels of estradiol and 11-ketotestosterone (11-KT) were significantly decreased in the ar mutants, indicating that steroidogenesis was defective in the mutants. Furthermore, the protein level of LHβ in the serum decreased markedly in the ar mutants when compared with wild-type fish, probably due to the positive feedback from the diminished steroid hormone levels. In summary, our results provided unequivocal in vivo evidence for the requirement of functional ar in maintaining normal spermatogenesis and steroidogenesis, in ensuring normal fertility in male zebrafish.

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      [1 ] State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
      [2 ] South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, China.
      [3 ] School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
      [4 ] School of Biomedical Sciences Core Laboratory, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, China.
      Biol. Reprod.
      Biology of reproduction
      Oxford University Press (OUP)
      Dec 06 2017
      29228103 4705880 10.1093/biolre/iox165


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