Iron overload modulates follicular microenvironment via ROS/HIF-1α/FSHR signaling

Yaoqiu Wu, Rong Yang, Jie Lan, Yingchen Wu, Jianyun Huang, Qi Fan, Fan Qi, Yang You, Haiyan Lin, Xuedan Jiao, Hui Chen, Chunwei Cao, Qingxue Zhang
Free radical biology & medicine · 2023 · vol. 196 , pp. 37–52 · doi:10.1016/j.freeradbiomed.2022.12.105 · PMID:36638901 · W4313898565
article OA: closed CC0 ⤵ 14 in-corpus citations
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This study investigated how excess iron disrupts the ovarian follicular microenvironment by affecting the ROS/HIF-1α/FSHR signaling pathway.

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Abstract

Iron is essential for the health of reproductive system, and women with iron overload suffer from ovarian dysfunction and lack effective treatment in fertility preservation. However, the underlying mechanism of the detrimental effects of iron overload on ovarian function remains ambiguous. Here, we confirmed the excess iron in the circumjacent follicle near endometriomas, which negatively impacted the oocyte development in the affected ovaries. Further, by integrating cell line and chronic iron overload mice model, we demonstrated that iron overload can function as a ROS inducer to amplify mitochondria damage, which significantly elevated the release of cytochrome C and ultimately induced the apoptosis of granular cells. Besides, for the first time, our findings revealed that disruption of HIF-1α/FSHR/CYP19A1 signaling was critical for decreased estrogen synthesis of granular cells in response to iron overload, which can lead to apparent oocyte maldevelopment and subfertility. Overall. this study uncovered that iron overload modulated the follicular microenvironment and generated a deleterious effect on female infertility via ROS/HIF-1α/FSHR signaling. These results might provide potential implications for future clinical risk management of patients with endometrioma and hemopathy.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload Iron Overload

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Cited by (14)

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