Institute for Anatomy, University of Veterinary Medicine Hannover, Hannover, Germany.
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Histol Histopathol. 2019 May;34(5):525-535. doi: 10.14670/HH-18-058. Epub 2018 Nov 7.
Impairment of blood-testis barrier integrity can be observed during inflammation, infection, trauma and experimental autoimmune orchitis, which is inducible in rodents. In the present study, an initially fertile two-year-old Beagle dog was presented with a decline in total sperm number resulting in azoospermia within five months, verified by twice-monthly semen analyses. The dog was clinically healthy with bilateral small testes and showed normal thyroid function. Bacterial cultures of semen were negative and serum biochemical analyses showed no abnormal findings. To determine causes of azoospermia, the dog was castrated. Histological examinations of hematoxylin-eosin stained testicular sections revealed impaired spermatogenesis, seminiferous tubules with spermatogenic arrest or Sertoli-cell-only syndrome as well as focal interstitial and even intratubular lymphocytic infiltrations. Germ cell sloughing, apoptosis and giant cells were also observed in some tubules. Subsequent immunostainings of smooth-muscle-actin, claudin3, claudin11 and connexin43 demonstrated, for the first time, a mechanical and functional disruption of the tubular wall and alterations of blood-testis barrier proteins in these tubules. Presence of claudin3 and claudin11 in canine testis was confirmed using RT-PCR and sequencing and/ or Western-blot analyses. All findings suggested a possible spontaneous autoimmune orchitis to be the underlying cause for the observed azoospermia.
在炎症、感染、创伤和实验性自身免疫性睾丸炎期间,可以观察到血睾屏障完整性的损害,这种损害在啮齿动物中是可诱导的。在本研究中,一只最初具有生育能力的两岁比格犬出现总精子数量下降,导致五个月内无精子症,这通过每月两次的精液分析得到证实。该犬临床健康,双侧睾丸较小,甲状腺功能正常。精液的细菌培养为阴性,血清生化分析也未发现异常。为了确定无精子症的原因,对该犬进行了去势手术。对经苏木精-伊红染色的睾丸切片进行组织学检查显示,精子发生受损,生精小管出现精子发生停滞或支持细胞综合征,以及局灶性间质和甚至管内淋巴细胞浸润。在一些小管中还观察到生殖细胞脱落、凋亡和巨细胞。随后的平滑肌肌动蛋白、闭合蛋白 3、闭合蛋白 11 和连接蛋白 43 的免疫染色首次表明,这些小管的管壁出现了机械和功能障碍,以及血睾屏障蛋白发生改变。使用 RT-PCR 和测序和/或 Western blot 分析证实了闭合蛋白 3 和闭合蛋白 11 在犬睾丸中的存在。所有发现均提示观察到的无精子症可能是自身免疫性睾丸炎的潜在原因。