Badran Wael A, Fahmy Ibrahim, Abdel-Megid Wael M, Elder Kay, Mansour Ragaa, Kent-First Marijo
The Egyptian In Vitro Fertilization and Embryo Transfer Centre, Hadayk El-Maadi, Cairo, Egypt.
J Androl. 2009 Jul-Aug;30(4):416-25. doi: 10.2164/jandrol.108.005843. Epub 2009 Jan 22.
Androgens play key roles in spermatogenesis, and they exert their effect via the androgen receptor (AR). The AR gene has a repetitive DNA sequence in exon 1 that encodes a polyglutamine tract. Instability in the glutamine (CAG) repeat unit length is polymorphic across ethnic groups. Previous studies of the relationship between the repeat unit length and male infertility have been contradictory. To establish the range of wild-type alleles in Egyptian men, we determined the range of repeat lengths in a population of normally fertile, ethnically selected Egyptian men. We also investigated the association between trinucleotide repeat length within the AR gene and male factor infertility in a population of ethnically selected Egyptian infertile men, who were compared with fertile, ethnic group-matched and age-matched controls. The study included 129 clinically selected infertile Egyptian men who were scheduled for intracytoplasmic sperm injection and 52 ethnically matched fertile controls. The experimental population was grouped according to sperm counts ranging from nonobstructive azoospermia to normozoospermia. The CAG repeat N-terminal domain region of the AR gene was amplified in peripheral blood DNA, and allele size was determined by fragment analysis. Allele size and single-nucleotide polymorphism and mutation rates were determined by sequencing individual amplified alleles. The mean CAG repeat length in the azoospermia group was 18.55 +/- 2.0; in the severe oligozoospermia group it was 18.21 +/- 3.42; in the oligozoospermia group it was 18.27 +/- 2.93; and in the infertile with normal sperm count group it was 17.72 +/- 2.0. In the control group, the mean CAG repeat length was 18.18 +/- 3.63. No significant correlation was found between CAG repeat length and the risk of male factor infertility in an ethnically defined population of Egyptian men. However, a significant and positive correlation between CAG repeat length and serum testosterone concentration was demonstrated. This suggests the involvement of epigenetic regulation linked to this region.
雄激素在精子发生过程中发挥关键作用，它们通过雄激素受体（AR）发挥作用。AR基因的外显子1中有一个重复的DNA序列，该序列编码一个多聚谷氨酰胺序列。谷氨酰胺（CAG）重复单元长度的不稳定性在不同种族群体中具有多态性。先前关于重复单元长度与男性不育之间关系的研究结果相互矛盾。为了确定埃及男性中野生型等位基因的范围，我们测定了一组经过种族筛选的正常生育埃及男性群体中的重复长度范围。我们还研究了AR基因内三核苷酸重复长度与经过种族筛选的埃及不育男性群体中男性因素不育之间的关联，并将这些不育男性与生育能力正常、种族匹配且年龄匹配的对照组进行比较。该研究纳入了129名临床筛选的计划接受卵胞浆内单精子注射的埃及不育男性以及52名种族匹配的生育能力正常的对照组。根据精子计数将实验人群分为从非梗阻性无精子症到正常精子症的不同组。在周边血DNA中扩增AR基因的CAG重复N端结构域区域，并通过片段分析确定等位基因大小。通过对单个扩增等位基因进行测序来确定等位基因大小、单核苷酸多态性和突变率。无精子症组的平均CAG重复长度为18.55±2.0；严重少精子症组为18.21±3.42；少精子症组为18.27±2.93；精子计数正常的不育组为17.72±2.0。对照组的平均CAG重复长度为18.18±3.63。在一个经过种族定义的埃及男性群体中，未发现CAG重复长度与男性因素不育风险之间存在显著相关性。然而，证实了CAG重复长度与血清睾酮浓度之间存在显著正相关。这表明与该区域相关的表观遗传调控参与其中。
