Alterations in oocyte mitochondrial number and function are related to spindle defects and occur with maternal aging in mice and humans†

Pasquariello, Rolando; Ermisch, Alison F; Silva, Elena; McCormick, S.; Logsdon, Deirdre M.; Barfield, Jennifer P.; Schoolcraft, William B.; Krisher, Rebecca L.

doi:10.1093/biolre/ioy248

Cited by 75 publications

(59 citation statements)

References 66 publications

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“…For example, the distribution of cortical granules (CGs) altered dramatically and CG contents became swollen in oocytes from old females (Díaz & Esponda, ). Mitochondrial DNA (mtDNA) copy number and function are reduced in eggs from aged mice after both in vivo and in vitro maturation (Pasquariello et al, ). In parallel with these observations, Nakagawa et al found that spindle microtubule dynamics altered substantially in old oocytes, resulting in transiently multipolar spindles that predispose the oocytes to missegregation of intact sister chromatid pairs (Nakagawa & FitzHarris, ).…”

Section: Discussionmentioning

confidence: 99%

Loss of HDAC3 contributes to meiotic defects in aged oocytes

Gao

et al. 2019

Aging Cell

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Maternal age-related decline in oocyte quality is associated with meiotic defects, but the underlying mechanisms remain to be explored. Histone deacetylase 3 (HDAC3) has been shown to govern multiple cellular events via deacetylating diverse substrates. We previously found that HDAC3 could promote meiotic apparatus assembly in mouse oocytes. In the present study, we identified a substantial reduction in HDAC3 protein in oocytes from old mice. Importantly, overexpression of HDAC3 in old oocytes not only partially prevents spindle/chromosome disorganization, but also significantly lowers the incidence of aneuploidy. Meanwhile, we noticed the elevated acetylation level of α-tubulin in oocytes derived from old mice. By employing sitedirected mutagenesis, we showed that acetylation-mimetic mutant tubulin-K40Q disrupts the kinetochore-microtubule attachments and results in the assembly failure of meiotic apparatus in mouse oocytes. Importantly, forced expression of tubulin-K40R (nonacetylatable-mimetic mutant) was capable of alleviating the defective phenotypes of oocytes from aged mice. To sum up, this study uncovers that loss of HDAC3 represents one potential mechanism mediating the effects of advanced maternal age on oocyte quality. K E Y W O R D Saneuploidy, HDACs, maternal aging, oocyte quality, reproduction

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Section: Discussionmentioning

confidence: 99%

Loss of HDAC3 contributes to meiotic defects in aged oocytes

Gao

et al. 2019

Aging Cell

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“…For example, the presence of sodium selenite in the medium has been shown to significantly increase the vitro maturation of mouse oocytes while suppressing the generation of ROS and increasing mtDNA copy number (Ghorbanmehr et al 2018), presumably through the stimulation of glutathione peroxidase activity (a key antioxidant enzyme with selenium in its active site). Positive impacts on the in vitro maturation of mammalian oocytes have also been recorded for α-tocopherol, either alone (Arias-Álvarez et al 2018) or mixed with additional antioxidants (alpha-lipoic acid, hypotaurine and N-acetyl cysteine) (Pasquariello et al 2019), 9-cis-retinoic acid (Gad et al 2018), coenzyme Q10 (Heydarnejad et al 2019 melatonin , rosmarinic acid ) and the antioxidant citrus flavonoid, hesperetin (Kim et al 2019). Antioxidants have also been shown to ameliorate the oxidative stress associated with oocyte vitrification (Trapphoff et al 2016, Ahmadi et al 2019 (Wu et al 2019).…”

Section: Antioxidantsmentioning

confidence: 99%

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

2020

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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.

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“…Previous research in ovine oocytes demonstrated that mtDNA copy number increases from the germinal vesicle (GV) to metaphase II (MII) stages of development (Cotterill et al 2013). However, a recent study looking at mouse and human oocytes found that mtDNA copy number decreased from the GV to MII stages in both species in younger and older maternal age groups; the authors suggested that the contrasting trend in mtDNA copy number may be attributed to species-specific mechanisms of oocyte mitochondrial degradation during the maturation process (Pasquariello et al 2018).…”

Section: Mitochondrial Dnamentioning

confidence: 98%

Mitochondria as a biomarker for IVF outcome

Kim

Seli

2019

Reproduction

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Mitochondria play an essential role in generating energy for embryo development and maintaining embryo metabolism through key cellular functions including ion homeostasis, amino acid metabolism, glycolysis, fatty acid metabolism, signal transduction and apoptotic regulation. Recent literature suggests that mitochondrial content and function may be related to implantation success and embryo viability. Some studies have linked increased levels of mitochondrial DNA to aneuploidy, advanced maternal age and euploid blastocyst with implantation failure, while others have failed to demonstrate similar findings. This review aims to provide an overview of the current literature surrounding the possibilities of using mitochondria as an additional biomarker for infertility treatment outcome and summarize the reasons as to why there are inconsistencies in these studies.

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Alterations in oocyte mitochondrial number and function are related to spindle defects and occur with maternal aging in mice and humans†

Cited by 75 publications

References 66 publications

Loss of HDAC3 contributes to meiotic defects in aged oocytes

Loss of HDAC3 contributes to meiotic defects in aged oocytes

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

Mitochondria as a biomarker for IVF outcome

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