Welter H, Huber A, Lauf S, Einwang D, Mayer C, Schwarzer J U, Köhn F M, Mayerhofer A
Anatomy III - Cell Biology, Ludwig Maximilian University, Schillerstrasse 42, 80336 Munich, Germany.
Anatomy III - Cell Biology, Ludwig Maximilian University, Schillerstrasse 42, 80336 Munich, Germany.
Mol Cell Endocrinol. 2014 Aug 5;393(1-2):171-8. doi: 10.1016/j.mce.2014.06.011. Epub 2014 Jun 24.
We observed that peritubular myoid cells in the human testis are immunoreactive for angiotensin II (AngII) receptors (AT1R) and explored AngII actions in cultured human testicular peritubular cells (HTPCs). In response to AngII they contracted within minutes. The AT1R-blocker losartan blocked contraction, implying involvement of AngII and AT1R in intratesticular sperm transport. AngII also significantly increased IL-6 mRNA levels and IL-6 secretion within hours and losartan again prevented this action. This suggests involvement in inflammatory processes, which may play a role in male infertility. AngII can be generated locally by mast cell (MC)-derived chymase (CHY), which cleaves AngI. In testicular biopsies from infertile men we found abundant MCs, which express CHY, within the wall of seminiferous tubules. In contrast, CHY-positive MCs are hardly found in normal human testis. Testicular inflammatory events may fuel processes resulting in impaired spermatogenesis. Therefore therapeutic interference with MCs, CHY or AT1R might be novel options in male infertility.
我们观察到，人类睾丸中的管周肌样细胞对血管紧张素II（AngII）受体（AT1R）具有免疫反应性，并研究了AngII在培养的人类睾丸管周细胞（HTPCs）中的作用。在AngII作用下，它们在数分钟内收缩。AT1R阻滞剂氯沙坦可阻断收缩，这意味着AngII和AT1R参与了睾丸内精子运输。AngII还在数小时内显著提高白细胞介素-6（IL-6）的mRNA水平和IL-6分泌，氯沙坦再次阻止了这一作用。这表明其参与了炎症过程，而炎症过程可能在男性不育中起作用。AngII可由肥大细胞（MC）衍生的糜酶（CHY）在局部产生，CHY可裂解血管紧张素I（AngI）。在不育男性的睾丸活检中，我们在生精小管壁内发现了大量表达CHY的MC。相比之下，在正常人类睾丸中几乎找不到CHY阳性的MC。睾丸炎症事件可能会加剧导致精子发生受损的过程。因此，对MC、CHY或AT1R进行治疗性干预可能是治疗男性不育的新选择。
