Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

Abstract

SummarySensitive non-heme iron histochemistry-namely, the perfusion-Perls method and perfusion-Turnbull method-was applied to study the distribution and age-related accumulation of non-heme ferric iron and ferrous iron in mouse ovary. Light and electron microscopic studies revealed that non-heme ferric iron is distributed predominantly in stromal tissue, especially in macrophages. By contrast, the distribution of non-heme ferrous iron was restricted to a few ovoid macrophages. Aged ovaries exhibited remarkable non-heme iron accumulation in all stromal cells. In particular, non-heme ferrous iron level was increased in stromal tissue, suggestive of increased levels of redox-active iron, which can promote oxidative stress. Moreover, intense localization of both non-heme ferric and ferrous iron was observed in aggregated large stromal cells that were then characterized as ceroid-laden enlarged macrophages with frothy cytoplasm. Intraperitoneal iron overload in adult mice resulted in non-heme iron deposition in the entire stroma and generation of enlarged macrophages, suggesting that excessive iron accumulation induced macrophage morphological changes. The data indicated that non-heme iron accumulation in ovarian stromal tissue may be related to aging of the ovary due to increasing oxidative stress. (J Histochem Cytochem 60:229-242, 2012) Keywords non-heme iron, ovary, aging, macrophage, sensitive non-heme iron histochemistry Article

Reproductive age-associated fibrosis in the stroma of the mammalian ovary

“…A similar population of enlarged macrophage cells was observed previously in the ovarian stroma of aged C57B/6J mice, thereby corroborating our findings in CB6F1 and CD1 mice (Asano 2012). These enlarged macrophages were also characterized by a frothy cytoplasm with polymorphic inclusion bodies and lysosomes, multiple nuclei, and intense autofluorescence (Asano 2012).…”

“…This observation is consistent with the well-documented role of macrophages in numerous ovarian processes including folliculogenesis, ovulation, and corpus luteum formation and regression (Wu, et al 2004). These macrophages had varying morphologies, including small spindle-shaped macrophages and ovoid macrophages, suggesting sub-populations with differing functions (Asano 2012) (Figures 7B, D). …”

“…These enlarged macrophages were also characterized by a frothy cytoplasm with polymorphic inclusion bodies and lysosomes, multiple nuclei, and intense autofluorescence (Asano 2012). It was also noted that there was a reproductive age-associated accumulation of non-heme iron in the ovarian stroma and that the subpopulation of enlarged macrophages had particularly high levels of nonheme ferric iron (NHF[III]), non-heme ferrous iron (NHF[II]), and oxidative stress (Asano 2012). This non-heme iron accumulation in the ovary with age may result from heme oxygenase-1-mediated heme degradation during follicular atresia and luteal regression (Asano 2012).…”

“…It was also noted that there was a reproductive age-associated accumulation of non-heme iron in the ovarian stroma and that the subpopulation of enlarged macrophages had particularly high levels of nonheme ferric iron (NHF[III]), non-heme ferrous iron (NHF[II]), and oxidative stress (Asano 2012). This non-heme iron accumulation in the ovary with age may result from heme oxygenase-1-mediated heme degradation during follicular atresia and luteal regression (Asano 2012). Disruption of iron homeostasis in several organs, including the liver, heart, and pancreas, leads to organ fibrosis (Ramm and Ruddell 2010).…”

Beta-Thalassemia Major and Female Fertility: The Role of Iron and Iron-Induced Oxidative Stress

“…Meanwhile, it has been suggested that OS modulates the age-related decline in fertility [20]. Additionally, a recent study indicated that nonheme iron accumulation on ovarian stromal tissue may be related to aging of the ovary due to increasing OS [38]. The age-related decline in fertility due to OS has a special impact in our group of patients, because of their increased age average due to significant improvements in chelation treatment modalities.…”