Shiraishi Koji, Matsuyama Hideyasu
Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
J Androl. 2012 Jan-Feb;33(1):66-73. doi: 10.2164/jandrol.110.011981. Epub 2011 Jan 27.
Microdissection testicular sperm extraction (micro-TESE) has revealed that spermatogenesis in nonobstructive azoospermia (NOA) patients is heterogeneous, even in the same testis, but there is no information regarding growth factors to support spermatogenesis. We investigated the involvement of epidermal growth factor (EGF)-like growth factors, which play important roles in cell proliferation and differentiation in NOA patients who underwent micro-TESE. Testicular samples were obtained from 5 fertile men (15 samples), 5 prostate cancer patients receiving maximum androgen blockade (10 samples), and 13 NOA patients who underwent micro-TESE (50 samples). The expression of the mRNA for EGF, heparin binding (HB)-EGF, amphiregulin, epiregulin, betacellulin, and transforming growth factor (TGF)-α were analyzed by real-time polymerase chain reaction analysis and adjusted using the expression of glyceraldehyde-3-phosphate dehydrogenase. Heterogeneous expression of these EGF-like growth factors were observed even in the same testis. The expression of HB-EGF, amphiregulin and TGF-α in NOA and prostate cancer patients was significantly lower than observed in fertile controls. In NOA patients, expression in the testicular sample comprising mature sperm was significantly higher than those without mature sperm, indicating that HB-EGF, amphiregulin, and TGF-α are considered to participate in creating a suitable niche for spermatogenesis. Considering the findings that ablation of gonadotropin inhibited and human chorionic gonadotropin stimulation increased these EGF-like growth factors, the expressions are presumably under gonadotropin regulation.
显微切割睾丸取精术（micro-TESE）已揭示，非梗阻性无精子症（NOA）患者的精子发生是异质性的，即使在同一睾丸中也是如此，但关于支持精子发生的生长因子尚无相关信息。我们研究了表皮生长因子（EGF）样生长因子在接受micro-TESE的NOA患者细胞增殖和分化中所起的作用。从5名有生育能力的男性（15份样本）、5名接受最大雄激素阻断治疗的前列腺癌患者（10份样本）以及13名接受micro-TESE的NOA患者（50份样本）获取睾丸样本。通过实时聚合酶链反应分析来检测EGF、肝素结合（HB）-EGF、双调蛋白、表皮调节素、β-细胞素和转化生长因子（TGF）-α的mRNA表达，并使用甘油醛-3-磷酸脱氢酶的表达进行校正。即使在同一睾丸中也观察到这些EGF样生长因子的异质性表达。NOA患者和前列腺癌患者中HB-EGF、双调蛋白和TGF-α的表达显著低于有生育能力的对照组。在NOA患者中，含有成熟精子的睾丸样本中的表达显著高于没有成熟精子的样本，这表明HB-EGF、双调蛋白和TGF-α被认为参与为精子发生创造合适的微环境。鉴于促性腺激素抑制和人绒毛膜促性腺激素刺激会增加这些EGF样生长因子的表达，推测这些表达受促性腺激素调节。
