Brunelli Roberto, Papi Massimiliano, Arcovito Giuseppe, Bompiani Adriano, Castagnola Massimo, Parasassi Tiziana, Sampaolese Beatrice, Vincenzoni Federica, De Spirito Marco
Dipartimento di Scienze Ginecologiche, Perinatologia e Puericultura, Università di Roma La Sapienza, Italy.
FASEB J. 2007 Dec;21(14):3872-6. doi: 10.1096/fj.07-8189com. Epub 2007 Jul 2.
Human cervical mucus is a heterogeneous mixture of mucin glycoproteins whose relative concentration changes during the ovulatory phases, thereby producing different mucus aggregation structures that can periodically permit the transit of spermatozoa for fertilization. In preovulatory phase, mucus is arranged in compact fiber-like structures where sperm transit is hindered. Previously, through observations made of fixed and dehydrated samples, a permissive structure in the ovulatory phase was attributed to the larger diameters of pores in the mucus network. Instead, by means of atomic force microscopy, we can show, for the first time, that unfixed ovulatory mucus is composed by floating globules of mucin aggregates. This finding sheds new light on the mechanism that governs spermatozoa transit toward the uterine cavity. In addition, we demonstrate that the switch from globular ovulatory to fibrous preovulatory mucus largely depends on a pH-driven mechanism. Analysis of mucin 5B primary sequence, the main mucin in ovulatory mucus, highlights pH-sensitive domains that are associated to flexible regions prone to drive aggregation. We suggest an involvement of these domains in the fiber-to-globule switch in cervical mucus.
人类宫颈黏液是黏蛋白糖蛋白的异质混合物，其相对浓度在排卵阶段会发生变化，从而产生不同的黏液聚集结构，这些结构能够周期性地允许精子通过以实现受精。在排卵前阶段，黏液排列成紧密的纤维状结构，阻碍精子通过。此前，通过对固定和脱水样本的观察，排卵阶段的一种允许精子通过的结构被归因于黏液网络中较大的孔隙直径。相反，借助原子力显微镜，我们首次发现未固定的排卵黏液由黏蛋白聚集体的漂浮小球组成。这一发现为控制精子向子宫腔移动的机制提供了新的线索。此外，我们证明从球状的排卵黏液到纤维状的排卵前黏液的转变很大程度上取决于pH驱动机制。对排卵黏液中的主要黏蛋白黏蛋白5B一级序列的分析突出了与易于驱动聚集的柔性区域相关的pH敏感结构域。我们认为这些结构域参与了宫颈黏液中纤维到小球的转变。
