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Globular structure of human ovulatory cervical mucus

Roberto Brunelli^*,1, Massimiliano Papi^,1, Giuseppe Arcovito, Adriano Bompiani, Massimo Castagnola^,,||, Tiziana Parasassi^¶, Beatrice Sampaolese^||, Federica Vincenzoni and Marco De Spirito^,2

^* Dipartimento di Scienze Ginecologiche, Perinatologia e Puericultura, Università di Roma La Sapienza, Italy;

Istituto di Fisica and

Istituto di Biochimica e Biochimica clinica, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy;

Istituto Scientifico Internazionale "Paolo VI," Rome, Italy; and

^|| Istituto per la Chimica del Riconsimento Molecolare and

^¶ Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy

²Correspondence: Istituto di Fisica, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy. E-mail: m.despirito{at}rm.unicatt.it

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.—Brunelli, R., Papi, M., Arcovito, G., Bompiani, A., Castagnola, M., Parasassi, T., Sampaolese, B., Vincenzoni, F., De Spirito, M. Globular structure of human ovulatory cervical mucus.

Key Words: atomic force microscopy • hydrophobicity • MUC5B • recurrence analysis.