Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients

Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients
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不育患者睾丸管周细胞收缩标记蛋白部分缺失

DOI:
10.1111/j.2047-2927.2012.00030.x
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发表时间:
2013
期刊:
影响因子:
4.5
通讯作者:
Mayerhofer A
Mayerhofer A
中科院分区:
医学2区
文献类型:
--
作者:
Welter H;Kampfer C;Lauf S;Feil R;Schwarzer JU;Köhn FM;Mayerhofer A

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睾丸小管壁纤维化重构在精子发生受损引起的男性不育中很常见。我们假设,这种形态变化见证了构建这一壁的细胞,即小管周围平滑肌样细胞的潜在根本改变状态。这可能包括这些细胞收缩能力的丧失,从而成为男性不育的一个因素。在这些病例中,小管壁上的免疫细胞增加,因此可能涉及局部免疫细胞相关因子,包括前列腺素(PG)代谢物。为了在人类中探索这些点,我们使用了睾丸活检,其中精子发生正常和精子发生受损的小管彼此相邻[混合萎缩(MA)],正常活检和培养的人类睾丸小管周围细胞。通过免疫组织化学可以很容易地检测到收缩所必需的蛋白质,肌球蛋白重链(MYH11),钙钙蛋白(Cal)和松弛,cGMP依赖性蛋白激酶1 (cGKI),并且在正常精子发生的活检的所有小管周围细胞中均匀分布。在所有活检中,血管平滑肌细胞也被染色,并作为重要的内在对照,这表明在精子发生受损的MA样本中,染色仅限于少数小管周围细胞或不存在。当精子发生正常时,可见常规的小管周围染色。这种模式提示复杂的调节影响,面对MA患者相同的全身激素情况,可能是由局部睾丸微环境引起的。PG代谢物15dPGJ2可能代表了这样一个因素,它降低了精子发生受损/未受损患者小管周围细胞中的Cal蛋白水平。有文献记载的MA患者小管周围平滑肌样细胞的表型转换可能会损害受累的精管收缩和放松的能力,现在必须将其视为男性不育复杂事件的一部分。
Fibrotic remodelling of the testicular tubular wall is common in human male infertility caused by impaired spermatogenesis. We hypothesized that this morphological change bears witness of an underlying fundamentally altered state of the cells building this wall, that is, peritubular smooth muscle‐like cells. This could include a loss of the contractile abilities of these cells and thus be a factor in male infertility. Immune cells are increased in the tubular wall in these cases, hence local immune cell‐related factors, including a prostaglandin (PG) metabolite may be involved. To explore these points in the human, we used testicular biopsies, in which tubules with normal spermatogenesis and impaired spermatogenesis are next to each other [mixed atrophy (MA)], normal biopsies and cultured human testicular peritubular cells. Proteins essential for contraction, myosin heavy chain (MYH11), calponin (Cal) and relaxation, cGMP‐dependent protein kinase 1 (cGKI), were readily detected by immunohistochemistry and were equally distributed in all peritubular cells of biopsies with normal spermatogenesis. In all biopsies, vascular smooth muscle cells also stained and served as important intrinsic controls, which showed that in MA samples when spermatogenesis was impaired, staining was restricted to only few peritubular cells or was absent. When spermatogenesis was normal, regular peritubular staining became obvious. This pattern suggests complex regulatory influences, which in face of the identical systemic hormonal situation in MA patients, are likely caused by the local testicular micromilieu. The PG metabolite 15dPGJ2 may represent such a factor and it reduced Cal protein levels in peritubular cells from patients with/without impaired spermatogenesis. The documented phenotypic switch of peritubular, smooth muscle‐like cells in MA patients may impair the abilities of the afflicted seminiferous tubules to contract and relax and must now be considered as a part of the complex events in male infertility.
睾丸收缩细胞和精子运输。
DOI: 10.1016/s0015-0282(16)42909-2
发表时间: 1977
影响因子: 6.7
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混合性萎缩患者的人类睾丸活检中的肥大细胞:数量、异质性以及环氧合酶 2 和前列腺素 D2 合酶的表达增加。
DOI: 10.1016/j.fertnstert.2011.05.035
发表时间: 2011
影响因子: 6.7
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肌球蛋白重链功能的分子遗传学解析
DOI: 10.1016/0092-8674(90)90583-z
发表时间: 1990
期刊: Cell
影响因子: 64.5
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精索静脉曲张男性睾丸中的管周肌样细胞:超微结构、免疫组织化学和定量研究
DOI: 10.1111/j.1365-2559.1992.tb00426.x
发表时间: 1992
期刊: Histopathology
影响因子: 6.4
作者:
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通讯作者: Ricardo Paniagua
DOI: 10.1093/humrep/der077
发表时间: 2011-06-01
期刊: HUMAN REPRODUCTION
影响因子: 6.1
作者:
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通讯作者: Middendorff, R.