1. Academic Validation
  2. Iron overload compromises preimplantation mouse embryo development

Iron overload compromises preimplantation mouse embryo development

  • Reprod Toxicol. 2021 Oct;105:156-165. doi: 10.1016/j.reprotox.2021.08.010.
Xiaopan Chen 1 Yier Zhou 2 Dandan Wu 3 Chongyi Shu 2 Ruifang Wu 2 Shishi Li 2 Qiongxiao Huang 2 Jing Shu 4
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310058, China; Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310058, China. Electronic address: chenxiaopan@hmc.edu.cn.
  • 2 Reproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310058, China.
  • 3 Department of Obstetrics, Zhejiang Hospital, Hangzhou 310012, China.
  • 4 Reproductive Medicine Center, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310058, China. Electronic address: Shujing@hmc.edu.cn.
Abstract

We and Others have previously shown that abnormal pelvic environment plays an important role in the unexplained infertility of endometriosis. However, whether iron overload caused by ectopic periodic bleeding found in patients with endometriosis participates in endometriosis-associated reproductive failure is unknown. This study aimed to investigate effects of iron at level relevant to pelvic iron overload on the development of preimplantation mouse embryo. Two-cell embryos were collected, and cultured to blastocysts in G1/G2 medium supplemented with iron alone or in combination with iron chelator. The development rates, ATP level, mitochondrial membrane potential (MMP), Reactive Oxygen Species level (ROS), and apoptotic and ferroptotic indices were compared between control and iron treatments across each specific developmental stage. Prolonged exposure to iron remarkably impaired early embryo development in vitro by hampering blastocyst formation (P < 0.001), which could be partly restored by iron chelator (P < 0.001). The arrest of embryo development was linked with iron-initiated mitochondrial dysfunction with reduction of ATP generation and MMP (P < 0.05 and P < 0.001, respectively). Impaired mitochondria altered ROS accumulation post-iron exposure at morula stage and blastocyst stage (P < 0.05). Moreover, Iron-exposed blastocyst stage embryos showed higher apoptotic and ferroptotic rates (P < 0.001 and P < 0.05, respectively). Our results highlight that pathologically relevant level of iron compromises preimplantation mouse embryo development by disrupting mitochondrial function and triggering both Apoptosis and Ferroptosis, which implicates that excess iron found in peritoneal fluid of women with endometriosis likely participates in endometriosis-associated reproductive failure.

Keywords

Apoptosis; Blastocyst; Endometriosis; Ferroptosis; Iron overload; Mitochondria; ROS.

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