The contribution of mitochondrial function to reproductive aging

Abstract

Purpose The number of women attempting to conceive between the ages of 36 and 44 has increased significantly in the last decade. While it is well established that women's reproductive success dramatically declines with age, the underlying physiological changes responsible for this phenomenon are not well understood. With assisted reproductive technologies, it is clear that oocyte quality is a likely cause since women over 40 undergoing in vitro fertilization (IVF) with oocytes donated by younger women have success rates comparable to young patients. Apart from oocyte donation, there is no known intervention to improve the pregnancy outcome of older patients. The aim of this paper was the review the relevant data on the potential role of mitochondria in reproductive aging. Method Review of current literature on the subject. Results We present the current evidence that associate mitochondrial dysfunction with age related decrease in female reproductive outcome. Conclusions The aging process is complex, driven by a multitude of factors thought to modulate cellular and organism life span. Although the factors responsible for diminished oocyte quality remain to be elucidated, the present review focuses on the potential role of impaired mitochondrial function.

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality

“…The main effect of the OreR nuclear genome to disrupt oogenesis, but not larval development, is consistent with the known tissue-specific characteristics of other metabolic dysfunctions in development and disease, and the sensitivity of oogenesis to metabolic stress, including that caused by mitochondrial dysfunction (Benkhalifa et al, 2014;Bentov et al, 2011;Boots et al, 2016;Grindler and Moley, 2013;McCall, 2004;Morrison and Spradling, 2008;Sieber et al, 2016). Although our rescue experiments showed that the allelic incompatibility between the Aatm V allele and simw 501 mitochondria causes the maternal effect embryonic lethality, preliminary observations suggest that the ovarian failure phenotype is multigenic and not just determined by alleles of Aatm.…”

“…However, in only a few cases have the specific genes responsible for mito-nuclear incompatibility been identified (Chou et al, 2010;Lee et al, 2008;Meiklejohn et al, 2013;Singh and Brown, 1991;Spirek et al, 2014). It is known that mitochondrial dysfunction can severely compromise female fertility, and that maternal inheritance of sub-functional mitochondria can reduce embryonic survival (Bentov et al, 2011;Demain et al, 2016;Ge et al, 2012;Tilly and Sinclair, 2013). An important unresolved issue is how incompatible interactions between specific alleles of mitochondrial and nuclear genes contribute to female reproductive failure.…”

The AUGMENTSM Treatment: Physician Reported Outcomes of the Initial Global Patient Experience

“…Other causes of poor egg/embryo quality beyond age-related factors include medical conditions such as type II diabetes, obesity, polycystic ovary syndrome (PCOS), as well as other genetic and environmental factors [6,7]. Over the past 25 years, an increasing body of clinical and preclinical data has demonstrated that the decline in egg quality is largely due to a reduction in energy production [8][9][10][11]. In the 1990s, there were attempts at improving egg and embryo quality by injecting cytoplasm from young, healthy, donor eggs into the eggs of women with a history of reproductive failures [12][13][14].…”

Reproductive aging is associated with decreased mitochondrial abundance and altered structure in murine oocytes

“…Previous research, recently reviewed by Bentov et al, has only partially defined how mitochondrial number and function in oocytes changes with maternal aging [2]. It is important to delineate whether aging leads to quantitative or qualitative changes or both in oocyte mitochondria.…”