{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:43:19Z","timestamp":1791240199156,"version":"4.1.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Estrogens are crucial regulators of ovarian function, mediating their signaling through binding to estrogen receptors. The disruption of the estrogen receptor 1 (\n                      <jats:italic>Esr1<\/jats:italic>\n                      ) 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\n                      <jats:italic>Esr1<\/jats:italic>\n                      -deficient ovaries showing massive expression of lipocalin 2, a regulator of iron homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Therefore, we examined the consequences of depleting\n                      <jats:italic>Esr1<\/jats:italic>\n                      in mouse ovaries, focusing on iron metabolism. For that reason, we compared ovaries of adult\n                      <jats:italic>Esr1<\/jats:italic>\n                      -deficient animals and age-matched wild type littermates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      We found increased iron accumulation in\n                      <jats:italic>Esr1<\/jats:italic>\n                      -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\n                      <jats:italic>Esr1<\/jats:italic>\n                      -deficient ovarian stroma. The depletion of\n                      <jats:italic>Esr1<\/jats:italic>\n                      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\n                      <jats:italic>Esr1<\/jats:italic>\n                      -deficient ovaries were characterized by iron accumulation and strong autofluorescence. Finally, deletion of\n                      <jats:italic>Esr1<\/jats:italic>\n                      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\n                      <jats:italic>Esr1<\/jats:italic>\n                      deficiency triggers mechanisms similar to those associated with aging.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2024.1325386","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T23:54:38Z","timestamp":1708646078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Ovaries of estrogen receptor 1-deficient mice show iron overload and signs of aging"],"prefix":"10.3389","volume":"15","author":[{"given":"Sarah 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