完全型圆头精子症患者精子表型、致病基因及辅助生殖治疗结局分析  

Analysis of sperm phenotype,pathogenic genes and assisted reproductive therapy outcomes in patients with total globozoospermia

作　　者：李耀宣 张小慧[1] 李大文[1] 黄悦悦[1] 王世凯[1] 覃捷[1] 毛献宝[1] 李政达 韦娉嫔 陈良师 施文 薛林涛[1] Li Yaoxuan;Zhang Xiaohui;Li Dawen;Huang Yueyue;Wang Shikai;Qin Jie;Mao Xianbao;Li Zhengda;Wei Pinpin;Chen Liangshi;Shi Wen;Xue Lintao(Reproductive Medical and Genetic Center,the People's Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China)

机构地区：[1]广西壮族自治区人民医院生殖医学与遗传中心,南宁530021

出　　处：《中华生殖与避孕杂志》2024年第1期67-72,共6页Chinese Journal of Reproduction and Contraception

基　　金：广西卫健委项目(S2021052);广西自然科学基金面上项目(2023GXNSFAA026011)。

摘　　要：目的探讨完全型圆头精子症患者临床表型、精子形态特征及辅助生殖技术治疗的效率。方法收集2019年11月至2022年5月期间在广西壮族自治区人民医院生殖医学与遗传中心就诊的完全型圆头精子症患者(完全型圆头精子症组),采集外周血进行遗传学检测,全外显子测序挖掘致病基因,并对精液常规、精子形态及超微结构进行分析;全部患者均接受了卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)联合人工卵子激活(artificial oocyte activation,AOA)治疗。选取同日取卵的行常规ICSI周期患者作为对照组,并采用时差动态监测系统监测发育全程动态参数,分析2组受精及胚胎发育效率、发育动力学参数及临床治疗结局。结果完全型圆头精子症组4例,对照组9例。完全型圆头精子症患者均合并精子活力低下、精子DNA碎片率升高,精子形态及顶体荧光染色均显示头部呈小圆形伴顶体区缺失;透射电子显微镜下圆头精子头部顶体完全缺失且多见核质松散、空泡化等异常,颈部线粒体鞘数量减少且排列杂乱,鞭毛轴丝“9+2”结构多见异常。4例患者中1例为DPY19L2基因纯合缺失,1例为DPY19L2基因新发纯合移码变异。完全型圆头精子症组受精率、双原核受精率、第3天优质胚胎率、第6天囊胚形成率、第6天优质囊胚形成率与对照组差异均无统计学意义(均P>0.05);完全型圆头精子症组胚胎发育早期时间参数第二极体释放时间、原核消失时间,2至6-细胞各时期时间显著早于对照组且差异均有统计学意义(均P<0.05),2组胚胎分裂模式差异无统计学意义(P>0.05)。4例完全性圆头精子症患者中,2例新鲜胚胎移植各活产健康男婴1名,2例解冻周期移植活产健康男婴、女婴各1名。结论完全型圆头精子症患者精子形态学异常表型特征明显,ICSI联合AOA是有效的辅助生殖治疗手段。Objective To analyze the clinical phenotype,sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center,the People's Hospital of Guangxi Zhuang Autonomous Region.Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes.Semen characteristics,sperm morphology and ultrastructure were analyzed.Four patients were treated with intracytoplasmic sperm injection(ICSI)combined with artificial oocyte activation(AOA).Conventional ICSI cycles(n=9)were selected as control group,and the development dynamic parameters were monitored by Time-lapse.The fertilization and embryo development parameters,developmental dynamic parameters and clinical outcomes were analyzed between the two groups.Results Four patients were complicated with low sperm motility and increased sperm DNA fragmentation.Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome.By the transmission electron microscope,it was observed that round-headed spermatozoas were lacked of acrosome completely,loose chromatin structure,vacuolation and other abnormal changes in the head,mitochondrial sheath in neck were reduced arranged in disorder,and the structure of"9+2"of the flagellar axial filament was incomplete.Of the 4 patients,1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene.There were no significance differences in fertilization rate,two pronuclei fertilization rate,day 3 high-quality embryo rate,day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group(all P>0.05).The developmental dynamic parameters as the time at which the second polar body is extruded,the time when both(or the las

关 键 词：精子注射 细胞质内 延时成像 圆头精子症 卵子人工激活 

分 类 号：R714.8[医药卫生—妇产科学]