Review Finds Ferroptosis Plays Significant Role in Male Infertility

According to the World Health Organization, nearly 20% of adults worldwide experience infertility. The organization predicts that infertility will become the third most prevalent disorder of the century, following cancer and cardiovascular disease. Several risk factors contribute to male infertility, including infections, varicocele, and lifestyle factors such as smoking.

In a review published last month in Cell Death Discovery, Wenzheng Yuan and his colleagues from the Key Laboratory of Fertility Preservation at Xinxiang Medical University in Xinxiang, China, explored the role of ferroptosis in male infertility.

Ferroptosis is a type of iron-dependent cell death triggered by iron build-up and lipid peroxidation (oxidation of lipids by free radicals). In the testes, iron is necessary for testosterone production and sperm cell development. However, surplus iron can lead to oxidative stress, resulting in lipid peroxidation.

In their review, Yuan and his colleagues wrote that certain factors, including exposure to toxins such as cadmium, the leukemia treatment busulfan (Busulfex, Myleran), and cigarette smoking, can promote ferroptosis.

According to the authors, increasing evidence exists pointing to the role of ferroptosis in male infertility. Based on this knowledge, they express that ferroptosis inhibition may be a promising pathway for treating and preventing male reproductive disorders. Yuan and his colleagues add that therapy with iron chelators, ferroptotic inhibitors, or antioxidants are plausible options that merit investigation for treating or preventing male infertility.

“Antioxidants or inhibition of ferroptosis with iron chelators may prevent and treat testicular diseases because inhibition of ferroptosis has been shown to significantly improve male reproductive function in various animal models. However, few clinical trials have been conducted to evaluate the therapeutic effects of ferroptotic inhibitors on male reproductive diseases. More population-based data are urgently needed to determine whether selective blocking of ferroptosis can reverse testicular dysfunction”, the researchers wrote in their conclusion.