The human endometrium undergoes dynamic hormonal and structural changes throughout the menstrual cycle. Their aim is to create an environment essential for embryo implantation. Successful implantation depends on the proper composition of the endometrial microenvironment, including cytokine synthesis and local immune responses. During the first trimester, uterine natural killer (uNK) cells play a key role in regulating trophoblast invasion, vascular remodelling, and establishing embryo tolerance, with nitric oxide (NO) also contributing to these processes. The study aimed to evaluate the expression patterns of NOS2 and NOS3 and their relationship to the infiltration of endometrium by uterine natural killer (uNK) cells during different menstrual phases. The endometrial tissue samples representing proliferative, early secretory, late secretory, menstrual, and hypersecretory phases were analysed by immunohistochemistry and fluorescence microscopy. NOS2 and NOS3 showed distinct cyclic patterns. NOS3 expression peaked in the early secretory phase, supporting tissue remodelling, while NOS2 expression increased progressively, reaching its maximum in the late secretory and menstrual phases. The number of uNK cells paralleled NOS2 expression, with a positive correlation suggesting a possible NO-related immunomodulatory mechanism. Elevated NOS2 expression and increased clustering of CD56+ uNK cells were observed in some cases of proliferative endometrium, possibly reflecting phase-inappropriate immune activation. These findings indicate that NOS activity and uNK cell dynamics may jointly contribute to the cyclic regulation of the endometrial microenvironment. Understanding NOS regulation and its hormonal and immune interactions may offer new insights into implantation mechanisms.

Institute of Pathological Anatomy Faculty of Medicine Comenius University in Bratislava Slovak Republic

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