Evaluation of inflammatory status and macrophage polarization in premature ovarian insufficiency mice induced by chemotherapy
- 1Department of Reproductive Medicine, Guangdong Women and Children Hospital, Guangzhou, China
- 2Department of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- 3Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
Abstract
Background: With an increasing trend of cancer occurring in young women, chemotherapy, a commonly used anticancer method, often leads to premature ovarian insufficiency (POI) and infertility. Until now, there has been, however, no available treatment to cure POI patients caused by chemotherapy. This highlights the urgent need to unravel the mechanism underlying chemotherapy-induced POI development.
Methods: The POI mouse model was established with cyclophosphamide and busulfan. The levels of key pro-inflammatory and anti-inflammatory cytokines in ovaries were determined using qPCR or immunohistochemistry (IHC), while the levels of other pro-inflammatory cytokines in the serum were measured by ELISA. The macrophages (MΦs) populations and polarization within ovaries were analyzed using flow cytometry and immunofluorescence.
Results: Initially, chemotherapy-treated mice exhibited ovarian dysfunction and a decline in ovarian reserve, characterized by disrupted hormone levels and follicular loss. Following chemotherapy, there was an increase of pro-inflammatory cytokines, including Il1b, Il6 and Tnfa in mouse ovaries. Similarly, a significant elevation of pro-inflammatory cytokines like IL-6 and IL-18 was observed in the serum of chemotherapy-induced POI mice. Moreover, we found that the proportion of CD11c+ M1-like MΦs was remarkably increased in ovaries of chemotherapy-induced POI mice compared to the controls. However, the proportion of CD206+ M2-like MΦs did not differ significantly between POI and control groups. Notably, ovarian MΦs exhibited differential distribution after chemotherapy. CD11c+ M1-like MΦs mainly localized around atretic follicles, while CD206+ M2-like MΦs predominantly accumulated in ovarian stroma, accompanied by increased fibrosis. However, the Pearson analysis revealed that within the POI group, there was no significant correlation among fibrosis area, CD206+ M2-like MΦs density and the levels of key pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in ovaries.
Conclusions: Our descriptive study indicates that exacerbated inflammation and stromal fibrosis, as well as increased CD11c+ M1-like MΦs polarization, occur in mouse ovaries during chemotherapy. Since these are associative findings, future interventional studies including MΦs depletion are required to examine whether a causal relationship exists between CD11c+ M1-like MΦs and ovarian damage or between CD206+ M2-like MΦs and ovarian fibrosis in chemotherapy-induced POI. Moreover, additional functional research is necessary to determine whether modulating ovarian inflammation and M1/M2-like MΦs polarization would ameliorate chemotherapy-induced POI.
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BibTeX
@article{tang2026evaluation,
title = {{Evaluation of inflammatory status and macrophage polarization in premature ovarian insufficiency mice induced by chemotherapy}},
author = {Maoxing Tang and Manzhi Zhao and Yangcheng Yao and Xiqian Zhang and Fenghua Liu},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1798400},
url = {https://doi.org/10.3389/fendo.2026.1798400},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evaluation of inflammatory status and macrophage polarization in premature ovarian insufficiency mice induced by chemotherapy
AU - Maoxing Tang
AU - Manzhi Zhao
AU - Yangcheng Yao
AU - Xiqian Zhang
AU - Fenghua Liu
PY - 2026
DA - 2026/10/12
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1798400
UR - https://doi.org/10.3389/fendo.2026.1798400
AB - Background: With an increasing trend of cancer occurring in young women, chemotherapy, a commonly used anticancer method, often leads to premature ovarian insufficiency (POI) and infertility. Until now, there has been, however, no available treatment to cure POI patients caused by chemotherapy. This highlights the urgent need to unravel the mechanism underlying chemotherapy-induced POI development. Methods: The POI mouse model was established with cyclophosphamide and busulfan. The levels of key pro-inflammatory and anti-inflammatory cytokines in ovaries were determined using qPCR or immunohistochemistry (IHC), while the levels of other pro-inflammatory cytokines in the serum were measured by ELISA. The macrophages (MΦs) populations and polarization within ovaries were analyzed using flow cytometry and immunofluorescence. Results: Initially, chemotherapy-treated mice exhibited ovarian dysfunction and a decline in ovarian reserve, characterized by disrupted hormone levels and follicular loss. Following chemotherapy, there was an increase of pro-inflammatory cytokines, including Il1b, Il6 and Tnfa in mouse ovaries. Similarly, a significant elevation of pro-inflammatory cytokines like IL-6 and IL-18 was observed in the serum of chemotherapy-induced POI mice. Moreover, we found that the proportion of CD11c+ M1-like MΦs was remarkably increased in ovaries of chemotherapy-induced POI mice compared to the controls. However, the proportion of CD206+ M2-like MΦs did not differ significantly between POI and control groups. Notably, ovarian MΦs exhibited differential distribution after chemotherapy. CD11c+ M1-like MΦs mainly localized around atretic follicles, while CD206+ M2-like MΦs predominantly accumulated in ovarian stroma, accompanied by increased fibrosis. However, the Pearson analysis revealed that within the POI group, there was no significant correlation among fibrosis area, CD206+ M2-like MΦs density and the levels of key pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in ovaries. Conclusions: Our descriptive study indicates that exacerbated inflammation and stromal fibrosis, as well as increased CD11c+ M1-like MΦs polarization, occur in mouse ovaries during chemotherapy. Since these are associative findings, future interventional studies including MΦs depletion are required to examine whether a causal relationship exists between CD11c+ M1-like MΦs and ovarian damage or between CD206+ M2-like MΦs and ovarian fibrosis in chemotherapy-induced POI. Moreover, additional functional research is necessary to determine whether modulating ovarian inflammation and M1/M2-like MΦs polarization would ameliorate chemotherapy-induced POI.
SN - 1664-2392
ER -