Assessment of apoptosis and cell proliferation in patients with intrauterine pathology: A prospective study

Background. In recent decades, the frequency of intrauterine pathology (IUP) has increased: endometrial hyperplasia and polyps, submucous uterine fibroids (SMUF), and other conditions that affect 38–72% of women of reproductive age. An imbalance in cell proliferation, differentiation, and death plays an important role in the pathogenesis of IUP.

Aim. To study and assess proteins regulating cell apoptosis and proliferation in patients of reproductive age with various IUPs.

Materials and methods. We analyzed the comprehensive examination data of 87 women of reproductive age (mean age 43.8±3.27 years) undergoing inpatient treatment at the N.V. Sklifosovsky Research Institute of Emergency Medicine from 2023 to 2024 with various IUPs. All patients underwent a general clinical and comprehensive instrumental examination (pelvic ultrasound, hysteroscopy, and/or hysteroresectoscopy with separate diagnostic curettage of the endocervix and endometrium and morphological examination of biopsy specimens). Plasma concentrations of proteins activating the external pathway of apoptotic cell death were measured: soluble Fas, soluble Fas ligand, and tumor necrosis factor-related apoptosis-inducing ligand. The growth factor levels were also measured: the main fibroblast growth factor, hepatocyte growth factor, and stem cell factor. A multiplex analysis was performed on the Luminex 200 platform (xMAP technology) using the MILLIPLEX MAP Human Circulating Cancer Biomarker Magnetic Bead Panel reagent kit. Based on the results of the morphological examination, patients were divided into four groups: Group 1 included 20 (22.9%) patients diagnosed with endometrial hyperplasia (EH) without atypia based on histological examination; Group 2 included 44 (50.6%) patients with endometrial polyps (EP); Group 3 included 16 (18.4%) patients with EP and concomitant EH without atypia; Group 4 included 7 (8.0%) patients with type 0–II SMUF according to the European Society of Hysteroscopy Classification of Submucous Fibroids with a node size of up to 3.5 cm. The comparison group for assessing the apoptosis of blood lymphocytes included 20 healthy females (HW) of reproductive age.

Results. In patients with EH without atypia and EP, dysregulation of cellular homeostasis was observed due to a change in the balance of factors of cell apoptosis and proliferation. A decrease in the concentration of apoptosis trigger factors and an increase in soluble Fas, which functions as a "trap," is associated with abnormal induction of programmed death of endometrial cells. Also, the decrease in factors activating cell apoptosis may be due to decreased growth factors involved in physiological regeneration. In patients with SMUF, no changes in the regulation of apoptotic cell death were detected, while a decrease in stem cell growth factor was noted.

Conclusion. The comprehensive use of instrumental methods improves the accuracy of diagnosis of various nosological forms of IUP. The analysis of the results supports further studies in patients with various types of IUP after surgical treatment and restoration of the menstrual cycle during the outpatient follow-up.