Immune and regenerative mechanisms in the pathogenesis of vulvovaginal atrophy: proteomic analysis ofcervicovaginal fluid

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Objective: Exploration of the relationship between clinical and anamnestic data, the severity of VVA, and the results of proteomic analysis of CVF to identify protein biomarkers associated with atrophic changes, inflammation, immune response, and tissue regeneration in the age group of 50–70 years.

Materials and methods: The methodological foundation of this study was a comprehensive analysis integrating the clinical and anamnestic data and proteomic analysis of cervicovaginal fluid (CVF) from patients with vulvovaginal atrophy (VVA). The study included 32 women aged 50–70 years with vulvovaginal atrophy (VVA). The comprehensive analysis included the clinical and anamnestic data, cytological examination, HPV genotyping, and analysis of the protein content of CVF. Semi-quantitative proteomic analysis (HPLC-MS/MS) including protein identification and annotation was performed using the MaxQuant and STRING software packages.

Results: Proteomic analysis of CVF identified specific protein profiles indicating activation of inflammatory processes, impaired tissue regeneration, and neurobiological mechanisms of pain sensitization. These profiles involved protein groups associated with blood microparticles and translocation of SLC2A4, both of which play an important role in occurrence of atrophic changes. Changes in PGAM1, PGAM2, and PGAM4 suggest impaired energy metabolism and the extracellular matrix synthesis, adversely affecting the proliferative activity of epithelial cells. Impaired glycine-serine metabolism reduces collagen and glutathione synthesis contributing to loss of tissue elasticity and increased susceptibility to oxidative stress. Changes in synthesis of HSPA1A and HSPA1B are associated with impaired cellular adaptive responses and lead to accumulation of damaged proteins and enhanced apoptotic death of vaginal epithelial cells.

Conclusion: Proteomic analysis identified specific protein profiles indicating inflammatory activation, impaired tissue regeneration, and neurobiological pathways of pain sensitization.

作者简介

Natalia Starodubtseva

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

编辑信件的主要联系方式.
Email: n_starodubtseva@oparina4.ru
ORCID iD: 0000-0001-6650-5915

PhD (Bio), Head of the Laboratory of Clinical Proteomics

俄罗斯联邦, Moscow

Niso Nazarova

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_nazarova@oparina4.ru
ORCID iD: 0000-0001-9499-7654

Dr. Med. Sci., Leading Researcher

俄罗斯联邦, Moscow

Anastasia Devyatkina

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grinasta26@mail.ru
ORCID iD: 0009-0006-1742-7555

obstetrician-gynecologist, PhD student

俄罗斯联邦, Moscow

Alisa Tokareva

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alisa.tokareva@phystech.edu
ORCID iD: 0000-0001-5918-9045

PhD (Phys.-Math.), Specialist at the Laboratory of Clinical Proteomics

俄罗斯联邦, Moscow

Evgenii Kukaev

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Moscow Institute of Physics and Technology

Email: e_kukaev@oparina4.ru
ORCID iD: 0000-0002-8397-3574

PhD (Phys.-Math.), PhD, Senior Researcher at the Laboratory of Clinical Proteomics

俄罗斯联邦, Moscow; Dolgoprudny

Anna Bugrova

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences

Email: a_bugrova@oparina4.ru

PhD (Bio), Senior Researcher at the Laboratory of Proteomics of Human Reproduction, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Senior Researcher, Laboratory of Neurochemistry, Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

俄罗斯联邦, Moscow; Moscow

Alexander Brzhozovskiy

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Skolkovo Institute of Science and Technology

Email: agb.imbp@gmail.com

PhD (Bio), Senior Researcher at the Laboratory of Proteomics of Human Reproduction, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Junior Researcher at the Laboratory of Mass Spectrometry, Skolkovo Institute of Science and Technology

俄罗斯联邦, Moscow; Moscow

Elena Mezhevitinova

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: mejevitinova@mail.ru
ORCID iD: 0000-0003-2977-9065

Dr. Med. Sci., Leading Researcher at the Scientific and Polyclinic Department

俄罗斯联邦, Moscow

Elmira Dovletkhanova

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: eldoc@mail.ru
ORCID iD: 0000-0003-2835-6685

PhD, Senior Researcher at the Scientific and Polyclinic Department

俄罗斯联邦, Moscow

Maria Kepsha

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: m_kepsha@oparina4.ru
ORCID iD: 0000-0002-4201-1360

Junior Researcher, doctor at the Scientific and Polyclinic Department

俄罗斯联邦, Moscow

Vladimir Frankevich

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Siberian State Medical University, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
ORCID iD: 0000-0002-9780-4579

Dr. Sci. (Phys.-Math.), Deputy Director of the Institute of Translational Medicine

俄罗斯联邦, Moscow; Tomsk

Vera Prilepskaya

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_prilepskaya@oparina4.ru
ORCID iD: 0000-0003-3993-7629

Dr. Med. Sci., Professor, Honored Scientist of the Russian Federation, Head of the Scientific and Polyclinic Department

俄罗斯联邦, Moscow

Gennady Sukhikh

Academician V.I. Kulakov National Medical Research Centre For Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: sekretariat@oparina4.ru
ORCID iD: 0000-0002-7712-1260

Dr. Med. Sci., Professor, Academician of the RAS, Director

俄罗斯联邦, Moscow

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