睾丸发育不全综合症与雄激素受体基因多态性及相关围产因素的研究

Study on the relationship among testicular dysgenesis syndrome, androgen receptor gene polymorphism and associated perinatal factors

目的探讨睾丸发育不全综合症（testiculardysgenesissyndrome，TDS）的幼年期发病（尿道下裂、隐睾）与雄激素受体（Androgenreceptor，AR）基因CAG重复长度多态性改变及相关围产因素的关系。方法收集2009年5月至2010年12月共60例尿道下裂、隐睾32例（单侧29例，双侧3例，其中尿道下裂合并单侧隐睾6例）及正常对照组70例，采血提取基因组DNA，检测AR基因CAG重复序列次数；收集围产资料，包括＆JL出生时体重及胎龄、母亲分娩时年龄、母孕早期保胎史（黄体酮使用）、是否人工辅助生育、母亲职业、居住地、孕期患妊娠高血压情况，并进行统计分析。结果尿道下裂组和隐睾组CAG重复次数均明显大于对照组（P分别为0．008和0．028）；相关围产因素中，尿道下裂的发生与低出生体重（P=0．003）、母亲低分娩年龄（P=0．007）及孕早期黄体酮使用（P=0．000）有关。隐睾与母亲低分娩年龄（P=0．003）及从事农业生产（P=0．017）有关。结论TDS的发生与多因素相关，当AR基因CAG重复次数增加，合并其他相关危险因素，如低出生体重、年轻的母亲，尤其是孕期暴露于雌激素或抗雄激素物质，如黄体酮、杀虫剂等，可能使发生TDS的风险累加而致病．

Objective To explore the relationships among the occurrence oftesticular dysgenesis syndrome with hypospadias and cryptorchidism, the polymorphic androgen-receptor CAG repeat and associated perinatal factors. Methods Blood samples were collected from 60 hypospadias, 32 cryptorchidism （unilateral 29 and bilateral 3, 6 of them combined with hypospadias） and 70 normal boys as control between May 2009 and Dec 2010. CAG repeat lengths of androgen receptor were measured. The perinatal data collected included birth weight and gestational age; mother＇s age, history of tocolysis in early trimester （the use of progesterone）, assisted reproduction, mother＇s occupation, habitation and history of gestational hypertension. All data were statistically analyzed. Results The CAG repeat length of hypospadias and cryptorchidism were significantly longer than the control （P = 0. 008 and 0. 028 respectively）. Low birth weight of infants （P = 0. 003）, mother＇s age （P = 0. 007） and the use of progesterone （P = 0. 000） were found to be risk factors for hypospadias. Mothers age （P = 0. 003） and agriculturalactivities （P = 0. 017） were risk factors for cryptorchidism. Conclusions The occurrence oftesticular dysgenesis syndrome is associated with multiple factors. The AR gene CAG repeat length, low birth weight, young mother, especially exposure to estrogen, anti androgen substances, such as progesterone and pesticide all contribute to an increased risk of the occurrence of testicular dysgenesis syndrome.