| First Author | Schröder SK | Year | 2024 |
| Journal | Front Endocrinol (Lausanne) | Volume | 15 |
| Pages | 1325386 | PubMed ID | 38464972 |
| Mgi Jnum | J:346193 | Mgi Id | MGI:7612849 |
| Doi | 10.3389/fendo.2024.1325386 | Citation | Schroder SK, et al. (2024) Ovaries of estrogen receptor 1-deficient mice show iron overload and signs of aging. Front Endocrinol (Lausanne) 15:1325386 |
| abstractText | INTRODUCTION: Estrogens are crucial regulators of ovarian function, mediating their signaling through binding to estrogen receptors. The disruption of the estrogen receptor 1 (Esr1) provokes infertility associated with a hemorrhagic, cystic phenotype similar to that seen in diseased or aged ovaries. Our previous study indicated the possibility of altered iron metabolism in Esr1-deficient ovaries showing massive expression of lipocalin 2, a regulator of iron homeostasis. METHODS: Therefore, we examined the consequences of depleting Esr1 in mouse ovaries, focusing on iron metabolism. For that reason, we compared ovaries of adult Esr1-deficient animals and age-matched wild type littermates. RESULTS AND DISCUSSION: We found increased iron accumulation in Esr1-deficient animals by using laser ablation inductively coupled plasma mass spectrometry. Western blot analysis and RT-qPCR confirmed that iron overload alters iron transport, storage and regulation. In addition, trivalent iron deposits in form of hemosiderin were detected in Esr1-deficient ovarian stroma. The depletion of Esr1 was further associated with an aberrant immune cell landscape characterized by the appearance of macrophage-derived multinucleated giant cells (MNGCs) and increased quantities of macrophages, particularly M2-like macrophages. Similar to reproductively aged animals, MNGCs in Esr1-deficient ovaries were characterized by iron accumulation and strong autofluorescence. Finally, deletion of Esr1 led to a significant increase in ovarian mast cells, involved in iron-mediated foam cell formation. Given that these findings are characteristics of ovarian aging, our data suggest that Esr1 deficiency triggers mechanisms similar to those associated with aging. |
