新理论或可彻底改变子宫内膜异位症的治疗方法

2021-05-12 Sunny MedSci原创

关于子宫内膜异位症表型的四个问题:系统发育史、发展、机制和适应性意义,对该疾病风险的进化和机制基础进行了首次分析和综合。

NEJM

子宫内膜异位症(endometriosis)是指有活性的内膜细胞种植在子宫内膜以外的位置而形成的一种女性常见疼痛性妇科疾病。 子宫内膜异位通常涉及卵巢,输卵管和盆腔的组织。 目前对此病发病的机制有多种说法,其中被普遍认可的是子宫内膜种植学说。

近日,加拿大西蒙弗雷泽大学生物科学系Bernard Crespi教授团队发表在《进化,医学和公共卫生》(Evolution, Medicine and Public Health)上的研究提出的新理论表明,睾酮在其发展中起着关键作用。这项研究可能对该疾病的诊断和治疗产生直接影响,为全世界患有子宫内膜异位症的女性带来希望。

子宫内膜异位症是由子宫内膜组织在子宫外生长引起的,通常是在盆腔区域,它会引起疼痛、炎症和不孕。但是为什么一些妇女会得这种病,而另一些则不会,这一点仍然不清楚。

新的研究基于最近的研究发现,与没有子宫内膜异位症的妇女相比,患有子宫内膜异位症的妇女在其母亲的子宫内的胎儿在相对较低的睾酮条件下发育。

该研究围绕尼古丁·丁伯格(Niko Tinbergen)关于表型的四个问题:系统发育史,发展,机制和适应性意义,对人类子宫内膜异位症风险的进化和机制基础进行了首次分析和综合。子宫内膜异位症的特征在于子宫外子宫内膜组织的增生,其系统发育根源于三个因果关系的演变:

(1)高侵袭性胎盘形成;

(2)自发性而非由植入驱动的子宫内膜蜕膜化;

(3 )频繁发生广泛的雌激素驱动的子宫内膜增生和炎症,继而发生大量月经出血。

子宫内膜异位症通过这些特征得到加强,并且似乎是由相对较低水平的产前和产后睾酮驱动的。睾酮会影响正在发育的下丘脑-垂体-卵巢(HPO)轴,在低水平时,它会导致生殖和生理表型的轨迹改变,在极端情况下会介导子宫内膜异位的症状。相比之下,从以前的研究中知道多囊卵巢综合征主要是由产前和产后睾酮偏高引起的,并且它证明了一组与子宫内膜异位症中发现的表型相反的表型。子宫内膜异位症风险由产前低睾酮引起,并涉及某些生殖表型的极端表达的假说得到了遗传学、发育、内分泌学、形态学和生活史的一系列证据的支持。

廷伯格根(Tinbergen)关于理解子宫内膜异位症及其相关表型的演变风险,发展,适应性意义和机制的四个问题的摘要。

最终,此处描述和评估的假设导致了许多可检验的预测,并对子宫内膜异位症的治疗和研究具有直接的意义。

根据研究人员的理论,这种低睾酮 "编码"了妇女发育中的生殖系统,使其表现出与子宫内膜异位症有关的独特特征,包括月经初潮提早,月经周期短,对疼痛高度敏感,炎症高,以及控制排卵和月经周期的激素水平改变。

研究人员发现他们的理论得到了文献中一系列显著数据的支持,从遗传学和发育到内分泌学、形态学、生活史和进化生物学,从而为与子宫内膜异位症有关的特征提供了第一个全面的解释。该理论可以解释几乎所有子宫内膜异位症的症状都是早期低睾酮的下游效应。

加拿大研究主席、SFU生物科学教授Bernard Crespi说:"早期发育中的低睾酮是已知的子宫内膜异位症最强的相关因素,其影响可以解释大多数子宫内膜异位症的症状,更重要的是,这个新理论对子宫内膜异位症的诊断和治疗有直接影响。",他与研究生Natalie Dinsdale是这项工作的共同作者。

Crespi指出,在对子宫内膜异位症的研究中,睾酮显然被忽视了,因为它通常被认为是一种 "男性"激素,尽管已知它对女性也有关键影响。

亚利桑那州立大学人类进化和社会变革学院的助理教授Ben Trumble称赞作者超越了二元激素的盲点,普遍情况下研究者把雌性激素作为一种女性激素,把睾丸激素作为一种男性激素,这是非常常见的,但实际上,这两种激素在所有人类中都是极为重要的,因此,这项研究的创新在于研究了能影响妇女健康的全部性激素。

通过对调节女性HPO轴的主要激素的影响,来确定产前睾丸激素如何介导子宫内膜异位和PCOS风险的模型。

这些模型显示了产前睾酮水平升高与降低对女性HPO轴发育的影响如何介导PCOS和子宫内膜异位症的风险,以及这些影响如何产生每种疾病的症状。

这项工作将子宫内膜异位症确立为一种发展性内分泌疾病,起源于生命的早期。它也阐明了子宫内膜异位症与多囊卵巢综合征的关系,多囊卵巢综合征是由产前睾丸激素水平过高而不是过低引起的。该研究显示,多囊卵巢综合征在其病因,相关因素和主要症状上与子宫内膜异位症基本相反。因此,这项工作应有助于改变我们对这两种疾病的理解。

原文出处:

The evolutionary biology of endometriosis.DOI:https://doi.org/10.1093/emph/eoab008

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    2021-05-12 SR~young海东

    医学进步

    0

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