摘要/Abstract
摘要： 目的 ·探究常染色体显性多囊肾病（ autosomal dominant polycystic kidney disease, ADPKD）致男性生殖障碍的机制以及分析辅助生殖技术的治疗结局。方法 ·对在上海交通大学医学院附属国际和平妇幼保健院行遗传咨询的 8例男性 ADPKD患者利用高通量测序进行基因诊断；手淫法收集 ADPKD患者及同时期行孕前咨询的正常男性的精液，分析精液参数；透射电子显微镜观察精子超微结构。选择进行胚胎植入前遗传学检测（ preimplantation genetic testing，PGT）的 7例 ADPKD患者与同一时期进入 PGT周期的 7例女性肌萎缩蛋白（ dystrophin, DMD）基因变异携带者，回顾性分析比较辅助生殖治疗结局。结果 · 8例 ADPKD患者均为多囊蛋白 1（polycystin 1，PKD1）基因杂合变异，精子运动参数（前向运动精子百分率、曲线速度、直线速度、平均路径速度、头侧摆幅度）远低于正常男性，表现为不同程度的少弱精子症，其中 1例严重少弱精子症的 ADPKD患者伴有双侧精囊囊肿。透射电子显微镜可见精子鞭毛的中央微管缺失和周围双联微管排列不齐。 ADPKD患者与女性 DMD基因携带者相比， PGT周期获卵数、受精率、卵裂率、有效胚胎率和优质胚胎率等差异均无统计学意义，但 ADPKD患者更易发生早期流产。结论 · ADPKD患者所致男性生殖障碍可能与精子鞭毛结构异常和精囊囊肿等因素相关，且 PKD1基因变异可能对胚胎着床及早期发育存在一定影响。
关键词: 常染色体显性多囊肾病, 多囊蛋白 1, 男性生殖障碍, 胚胎植入前遗传学检测
Abstract:
Objective · To explore the potential mechanism of male reproductive failure in autosomal dominant polycystic kidney disease (ADPKD) patients and analyze the outcomes of assisted reproductive technology treatment. Methods · Next-generation sequencing was performed for genetic diagnosis of 8 ADPKD patients, who came to International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, for genetic counseling. The semen of ADPKD patients and normal males who came for pre-pregnancy consultation was collectedmasturbation for sperm analysis. The ultrastructure of sperm was observedtransmission electron microscopy. Outcomes of 7 patients with ADPKD who chose preimplantation genetic testing (PGT) were compared with those of 7 patients who were dystrophin (DMD) gene mutation carriers, undergoing the PGT in the same period. Results · Eight patients with ADPKD were heterozygous for polycystin 1 (PKD1) gene. Key parameters of sperm motion including progressive motility sperm percentage, curvilinear velocity, straight-line velocity, average path velocity, amplitude of lateral head displacement were much lower than those of normal semen, showing mild to severe oligozoospermia. One ADPKD patient with severe oligoathenospermia manifested bilateral seminal vesicle cysts. Transmission electron microscopy showed that the central microtubules of the sperm flagella of ADPKD patients were absent and the surrounding double microtubules were disorganized. There was no significant difference in the number of eggs, fertilization rate, cleavage rate, effective embryo rate and excellent embryo rate between the ADPKD patients and the DMD gene mutation carriers, but the ADPKD patients were prone to early abortion. Conclusion · Male reproductive failure causedADPKD may be related to many factors such as abnormal structure of sperm flagella and genital cysts. Further, PKD1 mutation may play a role in embryo implantation and early development.
Key words: autosomal dominant polycystic kidney disease (ADPKD), polycystin 1 (PKD1), male reproductive failure, preimplantation genetic texting (PGT)
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