Age-Related Decline of Male Fertility: Mitochondrial Dysfunction and the Antioxidant Interventions

Abstract

Mitochondria are structurally and functionally unique organelles in male gametes. Apparently, as the only organelles remaining in mature sperm, mitochondria not only produce adeno-sine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to support sperm mobility, but also play key roles in regulating reactive oxidation species (ROS) signaling, calcium homeostasis, steroid hormone biosynthesis, and apoptosis. Mitochondrial dysfunction is often associated with the aging process. Age-dependent alterations of the epididymis can cause alterations in sperm mitochondrial functioning. The resultant cellular defects in sperm have been implicated in male infertility. Among these, oxidative stress (OS) due to the overproduction of ROS in mitochondria may represent one of the major causes of these disorders. Excessive ROS can trigger DNA damage, disturb calcium homeostasis, impair OXPHOS, disrupt the integrity of the sperm lipid membrane, and induce apoptosis. Given these facts, scavenging ROS by antioxidants hold great potential in terms of finding promising therapeutic strategies to treat male infertility. Here, we summarize the progress made in understanding mitochondrial dysfunction, aging, and male infertility. The clinical potential of antioxidant interventions was also discussed.

The Effect of Advancing Paternal Age on Seminal Fluid Parameters in Iraqi Males Attending Infertility Center: An Observational Study

“…Infertility is now the third most often diagnosed condition, with a global incidence of 15 percent; half of these situations are attributable to male causessee [3]. There was in-consensus regarding the criterion of advanced paternal age; forty years and above was the most often used criterion as what the current study adopted [3,11].…”

“…Our bodies endure various changes as we age, including alterations in the reproductive systems [1]. While women's fertility declines with age, men endure a more significant decline in their reproduction ability [2,3]. Earlier research has discussed negative impact of aging on seminal fluid parameters.…”

“…Earlier research has discussed negative impact of aging on seminal fluid parameters. These changes were attributed to reduced testosterone levels and other age-related hormonal changes [3,4]. In addition to increased erectile dysfunction caused by low testosterone and the effect of chronic diseases such as diabetes, heart disease, and ailments that interfere with reproduction, such as prostate and testicular cancer.…”

Bridging the Gap: Animal Models in Next-Generation Reproductive Technologies for Male Fertility Preservation

“…Animal studies report disordered gene expression and epigenetic changes derived from environmental endocrine disruptors, oxidative stress, and methylation errors in imprinted genes following in vitro embryo culture [136]. The morphological and genetic characteristics of the sperm, the age of the gamete, and the hormonal balance seem to be essential factors [137]. Little evidence supports a correlation between increased paternal age and the incidence of chromosome anomalies.…”

Are There Associations between Seminal Plasma Advanced Oxidation Protein Products and Selected Redox-Associated Biochemical Parameters in Infertile Male Patients? A Preliminary Report

“…Sperm cells are mitochondria-rich structures, and these cell organs enable proper sperm motility. In the case of oxidative stress, as a product of nicotinamide adenine dinucleotide (NAD)-dependent redox reactions, ROS damage mitochondria, leading to sperm motility disorders [ 12 , 13 , 14 ]. The effect of oxidative-antioxidative imbalance is also reflected in the sperm cells’ DNA damage, which affects both single- and double-stranded DNA molecules.…”