Iron Therapeutics in Women’s Health: Past, Present, and Future

Abstract

Iron plays a unique physiological role in the maintenance of homeostasis and the pathological outcomes of the female reproductive tract. The dual nature of elemental iron has created an evolutionary need to tightly regulate its biological concentration. The female reproductive tract is particularly unique due to the constant cycle of endometrial growth and shedding, in addition to the potential need for iron transfer to a developing fetus. Here, iron regulation is explored in a number of physiologic states including the endometrial lining and placenta. While iron dysregulation is a common characteristic in many women’s health pathologies there is currently a lack of targeted therapeutic options. Traditional iron therapies, including iron replacement and chelation, are common treatment options for gynecological diseases but pose long term negative health consequences; therefore, more targeted interventions directed towards iron regulation have been proposed. Recent findings show potential benefits in a therapeutic focus on ferritin-hepcidin regulation, modulation of reactive oxygen species (ROS), and iron mediated cell death (ferroptosis). These novel therapeutics are the direct result of previous research in iron’s complex signaling pathway and show promise for improved therapy, diagnosis, and prognosis in women’s health.

The Preparation, Antioxidant Activity Evaluation, and Iron-Deficient Anemic Improvement of Oat (Avena sativa L.) Peptides–Ferrous Chelate

“…Iron is helpful to maintain homeostasis and regulate a wide variety of physiologic and metabolic pathways, such as oxygen transport, oxidative phosphorylation, and many other enzymatic pathways (26,27). Besides, the dysregulation of iron pathways could lead to cellular oxidative stress (28).…”

“…Oxidative stress is mainly attributed to the generation of hydroxyl radicals and the initiation of lipid peroxidation. Lipid peroxidation creates mutagenic reactants, such as aldehyde malondialdehyde (MDA) ( 27 ). Hydroxyl and superoxide anion radicals can easily react with carbohydrates, proteins, and DNA, leading to oxidative stress, cell injury, and physiological disorders, all damages of which are harmful to the human body ( 12 ).…”

Urotensin II activates the ferroptosis pathway through circ0004372/miR-124/SERTAD4 to promote the activation of vascular adventitial fibroblasts

“…It has been found that UII promotes the generation of ROS (Yu et al 2015), and recent studies have shown that ROS is closely related to ferroptosis, a newly discovered pattern of cell death (Mintz et al 2020). In this study, UII was used to stimulate VAFs and found that UII activated the ferroptosis pathway, which significantly promoted the production of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased the concentration of Fe 2+ , and inhibited the expression of ferroptosis core regulatory factor GPX4.…”

“…Ferroptosis is a new way of cell death regulated by various systems in vivo. Its occurrence mainly depends on the action of related iron substances in vivo and the continuous generation and oxidation of ROS (Mintz et al 2020). Although UII activated ferroptosis, it promoted AF viability, which may be that UII promotes cell survival by activating other pathways.…”

Analysis of Environmental Determinants of Heme and Nonheme Iron Intake in a National Sample of Polish Adolescents

“…The study did not find any difference in iron intake, as well as in iron intake from various food products, in the subgroups stratified by meat intake in the region. Meat, particularly red meat, is rich in highly bioavailable heme iron [ 43 ], and thus, its adequate intake is necessary to prevent anemia [ 44 ], especially for women [ 45 ]. Studies show that a statistically significant difference in iron status can be observed between women of childbearing age who are following a diet that includes meat products, compared to those following a vegetarian diet [ 46 ].…”