Iron Overload-Induced Ferroptosis Impairs Porcine Oocyte Maturation and Subsequent Embryonic Developmental Competence in vitro

Abstract

Accumulating evidence indicates that ferroptosis is an iron-dependent form of regulated cell death. This type of iron-dependent programmed cell death is different from traditional forms of regulated cell death, such as apoptosis and autophagy. However, the role of ferroptosis in porcine oocyte maturation and the associated mechanism remain unclear. In the present research, we investigated the effects of ferric ammonium citrate (FAC), a specific ferroptosis inducer, on porcine oocyte meiotic maturation and quality and subsequent embryonic developmental competence. FAC treatment caused obvious accumulation of intracellular ferrous ions in porcine oocytes. At the end of the in vitro maturation (IVM) period, there was a significant decrease in the polar body (PB) extrusion rate and an increase in the percentage of abnormal oocytes in the FAC treatment groups, indicating that iron overload-induced ferroptosis may suppress the meiotic process during porcine oocyte maturation. We also found that after FAC treatment, the subsequent two-cell rate, four-cell rate and blastocyst formation rate were significantly decreased in porcine parthenogenetic activation (PA) embryos, indicating that iron overload-induced ferroptosis decreased porcine oocyte quality. Further analysis revealed that FAC treatment not only enhanced intracellular reactive oxygen species (ROS) generation, decreased intracellular free thiol levels and induced mitochondrial dysfunction but also triggered autophagy in porcine oocytes. Taken together, these findings suggest that iron overload-induced ferroptosis impairs porcine oocyte meiosis and decreases porcine oocyte quality, possibly by increasing oxidative stress, inducing mitochondrial dysfunction and triggering autophagy.

Ferroptosis-Related lncRNA for the Establishment of Novel Prognostic Signature and Therapeutic Response Prediction to Endometrial Carcinoma

“…The suppression of the proliferation of artesunate was accompanied by cell cycle blockade and modification of cell cycle molecules [ 38 ]. Hu et al found that iron overload-induced ferroptosis disrupted meiosis and lowered the quality of pig oocytes potentially owing to enhanced oxidative stress, mitochondrial malfunction, and autophagy activation [ 39 ]. The low-risk group in the predictive model had fewer KEGG enrichment values.…”

Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity

“…However, safety issues for infertile patients with EMs should be further considered. Our study demonstrates the harm of an iron overload environment to the oocyte, and relevant studies have proposed that iron overload-induced ferroptosis impairs oocyte maturation and development [ 49 ]. Iron overload was thought to play an important contributory role in shaping the EMs inflammatory microenvironment and cell adhesion [ 6 , 15 , 27 ].…”

BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency

“…Dysregulation of follicle fatty acids is a potential driver of human POI, as free fatty acid treatment reduces the proliferation rate and induces obvious apoptosis signals in granulosa cells isolated from the ovaries 56 . Iron overload-induced ferroptosis may suppress the meiotic process during porcine oocyte maturation and lead to oxidative stress in each stage of the follicles, thus disturbing follicle development [57][58][59] . Here, we found that BNC1 is required for maintaining mitochondrial function and lipid metabolism in oocytes and deficiency of BNC1 triggers ferroptosis-dependent POI.…”