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Review
. 2025 May 5:16:1589329.
doi: 10.3389/fimmu.2025.1589329. eCollection 2025.

Neutrophil extracellular traps in diseases of the female reproductive organs

Maria-Laura Morawiec  1 , Robert Kubina  2   3 , Sebastian Stępień  1 , Marta Smycz-Kubańska  1 , Patrycja Królewska-Daszczyńska  1 , Wioletta Ratajczak-Wrona  4 , Aleksandra Mielczarek-Palacz  1
Affiliations
Review

Neutrophil extracellular traps in diseases of the female reproductive organs

Maria-Laura Morawiec et al. Front Immunol. .

Abstract

Neutrophil extracellular traps (NETs) are physiologically released in response to pathogens, serving as a defense mechanism. However, excessive NET production has been implicated in various pathological conditions, including diseases of the female reproductive system. Recent studies highlight the significant role of neutrophils and NETs in cancer pathogenesis. Overproduction of NETs creates sites for tumor cell adhesion, promoting tumor cell proliferation, immune escape, and tumor progression. NET formation is associated with many diseases, including cancers of the female reproductive organs. Detection of NETs can be used as a prognostic tool for patients with diseases characterized by higher rates of NETs formation, such as cancer. In order to use NETs in diagnosis, it is possible to determine them directly or to determine NET components: extracellular DNA, citrullinated histones, NE or MPO. This review explores the role of neutrophils and NETs in the pathogenesis, diagnosis and treatment of breast, ovarian, cervical and endometrial cancer, premature lapse of ovarian function, cervicitis, endometriosis, pregnancy and pregnancy-related diseases.

Keywords: NETs; breast cancer; gynecological cancer; gynecological diseases; neutrophils.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Neutrophil granules The figure shows a neutrophil and the division of its granules, along with examples of substances that belong to them.
Figure 2
Figure 2
Neutrophils’ functions. The figure shows neutrophil functions, which include degranulation, phagocytosis, activation, formation of NETs, production of chemokines and cytokines, and crawling.
Figure 3
Figure 3
The role of pro-tumor and anti-tumor neutrophils The figure presents two neutrophil phenotypes: the anti-tumor phenotype (N1) and the pro-tumor phenotype (N2), and the role they may play in carcinogenesis.
Figure 4
Figure 4
NET structure. The figure presents the NET structure with the most important components that have been described.
Figure 5
Figure 5
Different types of NET formation. The figure shows the two basic types of NETs formation that we distinguish, lytic and vital, and the basic differences between them.
Figure 6
Figure 6
The positive and negative aspects of NETs. The figure depicts the positive aspects associated with NETs: trapping and neutralizing pathogens, their diagnostic and therapeutic potential, and the negative aspects associated with NETs, participation in various diseases, presented with their segregation.
Figure 7
Figure 7
Pro-cancer role of NETs. This figure shows pro-tumor features that are associated with NETS formation.
See this image and copyright information in PMC

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