Immunological aspects of uterine contractility during pregnancy and childbirth
Ivanova E.D., Baev O.R.
To maintain and successfully complete pregnancy, the maternal immune system undergoes strictly determined local and systemic changes. The development of transcriptomic, epigenomic, proteomic, and cytomic technologies enables a more detailed study of the complex mechanisms underlying immune adaptations during gestation. For a long time, the regulation of uterine tone was viewed primarily from the perspective of endocrine and neurohumoral control. However, the accumulated evidence suggests that the immune system plays an equally important role in modulating the contractile activity of the myometrium.
The review examines current understanding of the physiological role of aseptic inflammation in the initiation of labor, including the phenotypic switch of macrophages to the pro-inflammatory M1 type, increased expression of cytokines (IL-6, IL-1b, TNF-α) and the activation of TLR-dependent signaling pathways. It is emphasized that placental macrophages perform a dual function, namely morphogenetic and immune, by participating in angiogenesis and the remodeling of placental blood vessels, while their low reactivity in the first trimester is aimed at preventing damaging inflammation. Particular attention is paid to the mechanisms that limit an excessive inflammatory response: the CD163 receptor and its soluble form as a marker of the activation of M2 anti-inflammatory macrophages, as well as histidine metabolism, which exerts anti-inflammatory effects via carnosine and ensures the sensitivity of β-adrenoceptors in the myometrium. It has been shown that an imbalance in the CD163/histidine system leads to a disruption in the coordination between pro- and anti-inflammatory signaling and, consequently, to changes in uterine contractile function.
An imbalance between pro- and anti-inflammatory factors is regarded as a key factor in the pathogenesis of a wide range of obstetric complications: poor progress in labor, preterm birth, pregnancy loss and postpartum hemorrhage. For example, data are presented on the high prognostic significance of CD163 (AUC=0.969) and the combination of histidine with CD163 (AUC=0.926) in relation to the risk of postpartum hemorrhage.
Conclusion. An understanding of the immune mechanisms regulating uterine contractility opens new prospects for risk stratification, early diagnosis, and the development of pathogenetically grounded approaches to the prevention of complications associated with impaired myometrial tone.
Authors’ contributions. Baev O.R., Ivanova E.D. – developing the concept, literature review, writing the text, editing the article.
Conflicts of interest. Authors declare lack of the possible conflicts of interests.
Funding. The study was conducted without sponsorship.
Generative Artificial Intelligence. No generative artificial intelligence technologies were used in the preparation of this article.
For citation: Ivanova E.D., Baev O.R. Immunological aspects of uterine contractility during pregnancy and childbirth.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (9): 5-10 (in Russian)
https://dx.doi.org/10.18565/aig.2026.144
Keywords
uterine contractility
immune regulation
uterine tone
spontaneous labor
CD163
histidine
histamine
β-alanine
DPYD
cytokines
labor abnormalities
preterm birth
pregnancy loss
postpartum hemorrhage
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Received 28.04.2026
Accepted 03.09.2026
About the Authors
Ekaterina D. Ivanova, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, 117997, Russia, Moscow Ac. Oparina str., 4, +7(977)909-08-29, katrina.dip.13@gmail.com, https://orcid.org/0009-0006-0016-4701Oleg R. Baev, Dr. Med. Sci., Professor, Head of the 1st Maternity Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, 117997, Russia, Moscow Ac. Oparina str., 4; Professor at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), 119991, Russia, Moscow, Trubetskaya str., 8, build. 2, o_baev@oparina4.ru, https://orcid.org/0000-0001-8572-1971
Corresponding author: Ekaterina D. Ivanova, katrina.dip.13@gmail.com
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