Studies on the hormone and cytokine producing function of human cumulus cells and its interrelation with fertility in polycystic ovarian syndrome

Cumulus cells (CC) are the specialized layer of follicular cells that are in close contact with the oocyte. They are considered as indirect markers of the oocyte quality. Changes of these cells suggest a damage of the ovary. Determination of cytokines in cumulus cell culture may predict the chance for the conception and development of pregnancy. The objective of the present study was to obtain a primary culture of CC from healthy donors and patients with polycystic ovarian syndrome (PCOS), to identify the most significant differences in production of key cytokines in the CC monocultures of patients and healthy individuals in order to predict the results of in vitro fertilization. Materials and methods: the cell culture technique was used, i.e., cumulus cells of healthy donors and patients with polycystic ovary syndrome were obtained by transvaginal puncture of follicles in the in vitro fertilization (IVF) program. This procedure does not affect the rights of embryo, since the CC are not used at the stage of IVF procedure and intracytoplasmic sperm injection (Ethical Committee Protocol No. 9 of May 16, 2022). IL-6, IL-10, IFNγ and progesterone parameters were tested in adhesive cultures of CC by ELISA technique on days 1, 3, 7 of in vitro experiments. Results: We revealed a continuous secretion of progesterone, IL-6, IL-10, IFNγ in adhesive monocultures of CC. In the patients with PCOS, we have found a sharp increase of progesterone level in cultural media (p < 0.01) on the 7^th day, By contrast, the initially increased progesterone levels proved to be significantly decreased in donors on the 7^th day of culture. Moreover, in the culture of CC from patients with PCOS (7^th day of the experiment), the values of IL-6, IL-10 increased only two-fold compared with 30-fold increase of these cytokines in healthy donors (p < 0.01). At the same term, we have observed a threefold decrease in IFNγ in the CC cultures of PCOS patients (p_1-7 < 0.01; p < 0.05) compared with cultured controls, which showed a 20-fold increase (p_1-7 < 0.01), thus determining differences in total cytokine balance and, probably, influencing the pregnancy prognosis. Conclusion: Significant multidirectional changes of cytokine levels in the culture of cumulus cells of the patients with PCOS and in healthy individuals may be regarded as determining factors in formation of blastocyst and preservation of the embryo. A further in vitro research on the production of cytokines and sex steroids by CC is especially important on day 5 to 7, when the oocytes are selected for entry into the in vitro fertilization cycle. The study of morpho-functional properties of little-studied cumulus cells using the cell culture technique will enable us for a deeper study on the mechanisms of disturbed folliculogenesis in PCOS, and, thereby, improve the reproductive prognosis in this disorder.