Impact of oxidative stress on male and female germ cells: implications for fertility

Abstract

Male and female germ lines are vulnerable to oxidative stress. In spermatozoa, such stress triggers a lipid peroxidation cascade that culminates in the generation of electrophilic lipid aldehydes that bind to DNA and a raft of proteins involved in the delivery of functionally competent cells. One set of targets for these aldehydes are the proteins of the mitochondrial electron transport chain. When this interaction occurs, mitochondrial ROS generation is enhanced leading to the sustained generation of oxidative damage in a self-perpetuating cycle. Such damage affects all aspects of sperm function including motility, sperm-egg recognition, acrosomal exocytosis and sperm-oocyte fusion. Oxidative stress in the male germ line also attacks the integrity of sperm DNA with potential impacts on the developmental capacity of embryos and the health and wellbeing of the offspring. Potential pathways of reactive oxygen species (ROS) generation in male germ cells could involve enhanced lipoxygenase activity, activation of NADPH oxidase and/or electron leakage from mitochondria. Similarly, in the female germ line, both the induction of oocyte senescence following ovulation and the deterioration of oocyte quality with maternal age appear to involve the generation of oxidative damage. In this case, the mitochondria appear to be a particularly important source of ROS compromising the viability and fertilizability of the oocyte and interfering with the normal segregation of chromosomes during meiosis. In light of these considerations, antioxidants should have some role to play in the preservation of reproductive function in both men and women; however, we still await appropriate trials to test this hypothesis.

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

“…This mechanism has been elegantly demonstrated in the case of the sea urchin fertilization envelope where the dual oxidase, Udx1, has been shown to generate the hydrogen peroxide associated with the hardening of this membrane [51]. The existence of an analogous process in mammalian oocytes seems likely; however, while these cells are known to contain a variety of oxidases capable of generating ROS [52], their role during fertilization remains largely unexplored. Whatever mechanisms are involved, it is clear that many aspects of sperm biology including tyrosine phosphorylation, cholesterol exclusion, hyperactivation and sperm-egg interaction are redox regulated.…”

Sperm DNA Integrity and Male Fertility in Farm Animals: A Review

“…Excessive levels of ROS coupled with a deficiency in antioxidants can lead to oxidative stress resulting in nuclear and mitochondrial DNA damage, telomere shortening, epigenetic alterations and Y chromosomal microdeletions (33). Bovine sperm DNA integrity is affected by excessive exposure to ROS, obliterating DNA compaction or the repair of double-or singlestranded breaks during the reconfiguration of DNA, as occurs in cryopreservation of semen samples (34,35). A single-strand break is the outcome of an oxidative attack, whereas a doublestrand break is the indirect consequence of the products of lipid peroxidation e.g., 4-hydroxyl-2-nonenal (36).…”

Relationship between the metabolic and lipid profile in follicular fluid of women undergoing in vitro fertilization

“…Glycolic acid is a major precursor of oxalate that is able to induce more reactive oxygen species from mitochondria. The increase in oxidative stress due to the accumulation of ROS drives a series of events that induce a mechanism by which the oocytes enter apoptosis and lose their functionality (Aitken, 2020). The increase in oxidative stress due to both the production of androgens and an accumulation of lipids in the follicular environment can be one of the causes of reduced fertility.…”