Katagiri Yukiko, Neri Queenie V, Takeuchi Takumi, Moy Fred, Sills Eric Scott, Palermo Gianpiero D
The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, NY 10021, USA.
Int J Mol Med. 2006 Sep;18(3):405-13.
We determined the association of androgen receptor (AR) (CAG)n lengths among fertile and infertile males and offspring conceived by intracytoplasmic sperm injection (ICSI). Assessment of (CAG)n repeats in the AR was performed in a Caucasian population by gene sequencing in fertile men (n=13), infertile men (n=64), boys conceived after ICSI (n=21), and boys conceived naturally (n=11). In the AZF region of the Y chromosome, a total of 22 STSs were analyzed by multiplex PCR; selected spermatozoa were also analyzed by fluorescent in situ hybridization (FISH) for chromosomes 18, 21, X, and Y. The average age was 43.7+/-7 yr for infertile, 44.8+/-7 yr for fertile men, and 5.0+/-0.5 yr for the children. The mean (CAG)n was 22.2+/-3 for the infertile men and 19.3+/-5 for fertile controls. There was a significant difference in CAG repeat length in the severely oligo-/azoo-spermic men vs. controls (p=0.02). An inverse correlation was evident between CAG length and semen parameters. For ICSI male children, the AR (CAG)n lengths were 21.4+/-3.2 vs. 20.8+/-3.4 for boys conceived naturally. While all peripheral karyotypes of fertile and infertile men were normal, de novo gonosomal abnormalities were observed in the ICSI offspring. The incidence of Y microdeletions was 1.6% in infertile men; all the ICSI sons had an intact Y chromosome. In conclusion, severely oligo- and azoospermic men had longer CAG repeat length than fertile controls, suggesting that certain AR gene mutations may have a negative effect on spermatogenesis. An increased incidence of de novo gonosomal abnormalities was found in the ICSI offspring when compared to children conceived naturally. Our assessment of the polymorphic region of the AR gene, in the absence of other specific genomic abnormalities, suggests that the fertility of children conceived by ICSI may be conserved.
我们确定了可育和不育男性以及通过胞浆内单精子注射（ICSI）受孕的后代中雄激素受体（AR）（CAG）n长度的关联。通过基因测序对高加索人群中的可育男性（n = 13）、不育男性（n = 64）、ICSI受孕男孩（n = 21）和自然受孕男孩（n = 11）进行AR中（CAG）n重复序列的评估。在Y染色体的AZF区域，通过多重PCR分析了总共22个序列标签位点（STSs）；还通过荧光原位杂交（FISH）对所选精子进行了18号、21号、X和Y染色体分析。不育男性的平均年龄为43.7±7岁，可育男性为44.8±7岁，儿童为5.0±0.5岁。不育男性的平均（CAG）n为22.2±3，可育对照组为19.3±5。重度少精子症/无精子症男性与对照组的CAG重复长度存在显著差异（p = 0.02）。CAG长度与精液参数之间存在明显的负相关。对于ICSI男性儿童，AR（CAG）n长度为21.4±3.2，而自然受孕男孩为20.8±3.4。虽然可育和不育男性的所有外周核型均正常，但在ICSI后代中观察到了新发的性染色体异常。不育男性中Y微缺失的发生率为1.6%；所有ICSI儿子的Y染色体均完整。总之，重度少精子症和无精子症男性的CAG重复长度比可育对照组更长，这表明某些AR基因突变可能对精子发生有负面影响。与自然受孕儿童相比，ICSI后代中发现新发的性染色体异常发生率增加。我们对AR基因多态性区域的评估表明，在没有其他特定基因组异常的情况下，ICSI受孕儿童的生育能力可能得以保留。
