Sansone A, Isidori A M, Kliesch S, Schlatt S
Centre of Reproductive Medicine and Andrology, University Hospital of Münster, Albert-Schweitzer Campus 1, 48149, Münster, Germany.
Department of Experimental Medicine, Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, Italy.
Endocrine. 2020 Apr;68(1):215-221. doi: 10.1007/s12020-020-02210-x. Epub 2020 Feb 6.
In males, AMH is secreted by immature Sertoli cells; following exposure to endogenous androgens, Sertoli cells undergo a process of maturation which ultimately inhibits AMH expression to undetectable levels in the serum. However, expression of AMH receptor (AMHR-2) has never been studied in human testes, and high intratubular concentrations of AMH have been reported in recent literature. We therefore assessed expression of AMHR-2 in several testicular tissue samples by immunohistochemistry (IHC).
The IHC method was first validated on tissue samples from healthy human testis (n = 2) and from marmoset ovary (n = 1). The same method was then used for assessment on testicular histopathology specimens from patients with mixed atrophy (MA, n = 2), spermatogenetic arrest (SA, n = 2), Sertoli cell-only syndrome (SCO, n = 1), Klinefelter syndrome (KS, n = 1), and nonseminomatous germ cell tumors (NSGCT, n = 1). Tissue samples from two subjects at different pubertal stages (AndroProtect (AP), aged 5 and 14 years) with hematological malignancies were also retrieved.
In adult men, AMHR-2 was expressed on peritubular mesenchymal cells, with patterns closely mirroring α-smooth muscle actin expression. Similar patterns were preserved in almost all conditions; however, in nonseminomatous germ cell tumors the tissue architecture was lost, including AMHR-2 expression. More positive and diffuse staining was observed in tissue samples from prepubertal testes.
In specimens from both healthy and affected testes, AMHR-2 expression appears weaker in adult than in prepubertal tissue sections. The persistence of AMHR-2 expression seemingly hints at a possible effect of intratesticular AMH on the tubular walls.
在男性中,抗苗勒管激素(AMH)由未成熟的支持细胞分泌;在暴露于内源性雄激素后,支持细胞经历成熟过程,最终将AMH表达抑制至血清中无法检测到的水平。然而,AMH受体(AMHR - 2)在人类睾丸中的表达从未被研究过,并且最近的文献报道了睾丸内AMH浓度很高。因此,我们通过免疫组织化学(IHC)评估了几种睾丸组织样本中AMHR - 2的表达。
免疫组织化学方法首先在来自健康人类睾丸(n = 2)和狨猴卵巢(n = 1)的组织样本上进行验证。然后使用相同的方法对患有混合性萎缩(MA,n = 2)、生精停滞(SA,n = 2)、唯支持细胞综合征(SCO,n = 1)、克兰费尔特综合征(KS,n = 1)和非精原细胞瘤性生殖细胞肿瘤(NSGCT,n = 1)患者的睾丸组织病理学标本进行评估。还获取了两名处于不同青春期阶段(AndroProtect(AP),年龄分别为5岁和14岁)患有血液系统恶性肿瘤患者的组织样本。
在成年男性中,AMHR - 2在睾丸周围间质细胞上表达,其模式与α - 平滑肌肌动蛋白的表达密切相似。几乎在所有情况下都保留了类似的模式;然而,在非精原细胞瘤性生殖细胞肿瘤中,组织结构丧失,包括AMHR - 2的表达。在青春期前睾丸的组织样本中观察到更多阳性和弥漫性染色。
在健康和患病睾丸的标本中,AMHR - 2的表达在成人组织切片中似乎比青春期前组织切片中弱。AMHR - 2表达的持续存在似乎暗示睾丸内AMH对管壁可能有影响。