Unit for Basic and Applied Microbiology, School of Natural Sciences , Autonomous University of Queretaro , Avenida de las Ciencias S/N, Queretaro 76230, Mexico.
Department of Pathology , Instituto Mexicano del Seguro Social , Queretaro 76000, Mexico.
R Soc Open Sci. 2016 Mar 9;3(3):150419. doi: 10.1098/rsos.150419. eCollection 2016 Mar.
An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly 'protective' effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions.
在过去的二十年中，在加利福尼亚海岸搁浅的自由放养加利福尼亚海狮中，观察到转移性泌尿生殖道癌的发病率异常高。在相对无污染的加利福尼亚湾，尚未报告海狮病例。我们调查了来自加利福尼亚湾的 60 只海狮（n=57 只幼崽和 3 只成年雌性）的生殖器上皮转化的发生情况，并检查了先前发现与泌尿生殖道癌相关的病毒病原体感染是否导致了这种改变。我们还探讨了 MHC 类 II 基因表达对转化的贡献。在 42％的幼崽和 67％的成年雌性中观察到细胞改变，例如鳞状细胞异型性（ASC），非典型鳞状细胞意义不明（ASCUS）和低级别鳞状上皮内病变。在雄性幼崽中，正常的生殖器上皮比雌性幼崽更常见。ASC 在年龄较大的幼崽中发生的可能性是五倍。上皮改变与潜在致癌的海狮 I 型γ疱疹病毒（OtHV-1）感染无关，但 ASCUS 在有明显和严重炎症的幼崽中更为常见。外周抗原呈递白细胞中 MHC 类 II DRB 基因座（Zaca DRB-D）的表达显示 ASC 具有轻微的“保护”作用。我们提出，加利福尼亚海狮生殖器上皮的转化在年轻动物中相对常见，随年龄增长而增加，可能是由未识别的病原体感染引起的。特定 MHC 类 II 基因的表达，提示向免疫效应物呈递特定抗原肽，似乎降低了转化的风险。我们的研究首次证明，加利福尼亚海狮生殖道上皮的转化相对常见，甚至在早期，这引发了有关不同地理区域海狮癌症检测和修复成功的差异的问题。
