精子纤维鞘发育不良的形态学和遗传学初步研究(附3例报道)

A preliminary study on morphology and genetics of dysplasia of the fibrous sheath (3 cases report)

目的 分析纤维鞘发育不良患者精子形态学特点,探寻其致病基因.方法 对3例表现为严重弱精子症的患者进行光镜下精液分析,通过扫描电镜和透射电镜进一步明确其超微结构特点.候选基因精子鞭毛蛋白2（SPEF2）和减数分裂特异性蛋白1（MNS1）全外显子测序,分析可能的致病突变位点.结果 3例患者均表现为100％（或接近）不活动精子,精子存活率26.0％～80.0％.光镜和扫描电镜下可见无尾、粗短尾、卷尾和不规则尾等严重畸形,DFS缺陷精子分别占99.5％,97.5％和79.5％.透射电镜表现为精子鞭毛纤维鞘等多种结构组装异常,伴有中心微管缺失（59％～78％）和动力蛋白臂缺失.MNS1和SPEF1基因外显子未见病理性突变.结论 DFS是严重弱精子症原因之一,根据形态学特点可以诊断;遗传学病因有待研究.

Objective To analyze the sperm morphological characteristics of dysplasia of the fibrous sheath （DFS）, and explore the possible genetic origin. Methods Three patients with DFS were identified among severe asthenospermia cases, and their semen samples were collected. Ultra-structural features of semen were studied by scanning and transmission electron microscopy （SEM and TEM）. Exons of candidate genes MNS 1 and SPEF2 were sequenced to search the mutations. Results Analysis of semen samples from all the three patients showed 100% （or nearly） immotility in sperms, and 26%-80% viability in sperms. The morphological assessment under light and SEM presented severe distorted sperm tails, such as absence, short and thick, coiled, and irregular. The affected spermatozoa were 99.5%, 97.5% and 79.5% respectively. In TEM assays, most spermatozoa showed disorganized fibrous sheath, accompanied by distortion of various cytoskeletal components. The absence of central microtubules （59% to 78%） and dynein arms were observed. No likely pathogenic variants in MNS1 and SPEF2 were identified. Conclusion DFS is one cause of severe asthenospermia, and the genetic origin deserves further study.