Macrophages: a double-edged sword in female reproduction and disorders
Abstract Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue b...
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Nature Publishing Group
2025-02-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-025-01392-6 |
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| author | Mira Park Yeon Sun Kim Haengseok Song |
| author_facet | Mira Park Yeon Sun Kim Haengseok Song |
| author_sort | Mira Park |
| collection | DOAJ |
| description | Abstract Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue breakdown and repair without scarring. Owing to their phagocytic activity, macrophages, key players in innate immunity, are thought to play crucial roles in the endometrium. Endometrial macrophages actively participate in various stages of reproductive tissue remodeling, particularly during decidualization and pregnancy establishment. Traditionally considered simple bystanders that clear debris to prevent autoimmune responses in tissue homeostasis, macrophages are now recognized as main actors with broad functional plasticity that allows them to fine tune the balance between pro- and anti-inflammatory responses during tissue inflammation, remodeling and repair. Homeostatic balance is determined by the sum of various mediators produced by two distinctly polarized macrophage subpopulations. The biased polarization of tissue-resident macrophages may contribute to the pathogenesis of various diseases, such as inflammation and cancer. Thus, understanding how macrophages contribute to endometrial homeostasis is crucial for deciphering the underlying mechanisms of various reproductive disorders. Nanomedicines using extracellular vesicles, nanoparticles and noncoding RNAs have recently been applied to modulate macrophage polarization and alleviate disease phenotypes. Despite these advances, the functions of endometrial macrophages under physiological and pathophysiological conditions remain poorly understood, which complicates the development of targeted therapies. Here we update the current understanding of the homeostatic function of macrophages and the putative contribution of endometrial macrophage dysfunction to reproductive disorders in women, along with innovative molecular therapeutics to resolve this issue. |
| format | Article |
| id | doaj-art-da6207fa02154e5c8b8957289c19b33a |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
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| series | Experimental and Molecular Medicine |
| spelling | doaj-art-da6207fa02154e5c8b8957289c19b33a2025-08-20T03:05:57ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-02-0157228529710.1038/s12276-025-01392-6Macrophages: a double-edged sword in female reproduction and disordersMira Park0Yeon Sun Kim1Haengseok Song2Department of Biomedical Science, College of Life Science, CHA UniversityDepartment of Biomedical Science, College of Life Science, CHA UniversityDepartment of Biomedical Science, College of Life Science, CHA UniversityAbstract Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue breakdown and repair without scarring. Owing to their phagocytic activity, macrophages, key players in innate immunity, are thought to play crucial roles in the endometrium. Endometrial macrophages actively participate in various stages of reproductive tissue remodeling, particularly during decidualization and pregnancy establishment. Traditionally considered simple bystanders that clear debris to prevent autoimmune responses in tissue homeostasis, macrophages are now recognized as main actors with broad functional plasticity that allows them to fine tune the balance between pro- and anti-inflammatory responses during tissue inflammation, remodeling and repair. Homeostatic balance is determined by the sum of various mediators produced by two distinctly polarized macrophage subpopulations. The biased polarization of tissue-resident macrophages may contribute to the pathogenesis of various diseases, such as inflammation and cancer. Thus, understanding how macrophages contribute to endometrial homeostasis is crucial for deciphering the underlying mechanisms of various reproductive disorders. Nanomedicines using extracellular vesicles, nanoparticles and noncoding RNAs have recently been applied to modulate macrophage polarization and alleviate disease phenotypes. Despite these advances, the functions of endometrial macrophages under physiological and pathophysiological conditions remain poorly understood, which complicates the development of targeted therapies. Here we update the current understanding of the homeostatic function of macrophages and the putative contribution of endometrial macrophage dysfunction to reproductive disorders in women, along with innovative molecular therapeutics to resolve this issue.https://doi.org/10.1038/s12276-025-01392-6 |
| spellingShingle | Mira Park Yeon Sun Kim Haengseok Song Macrophages: a double-edged sword in female reproduction and disorders Experimental and Molecular Medicine |
| title | Macrophages: a double-edged sword in female reproduction and disorders |
| title_full | Macrophages: a double-edged sword in female reproduction and disorders |
| title_fullStr | Macrophages: a double-edged sword in female reproduction and disorders |
| title_full_unstemmed | Macrophages: a double-edged sword in female reproduction and disorders |
| title_short | Macrophages: a double-edged sword in female reproduction and disorders |
| title_sort | macrophages a double edged sword in female reproduction and disorders |
| url | https://doi.org/10.1038/s12276-025-01392-6 |
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