Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission

Chiaratti, Marcos Roberto

doi:10.1007/s12551-021-00891-w

Cited by 10 publications

(5 citation statements)

References 181 publications

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“…The abnormal expression of Mfns not only affects the reproductive success of the parents, but also has an impact on the health of the offspring. Chiaratti et al [ 126 ] previously showed that the oocyte-specific deletion of Mfn2 caused weight gain and glucose intolerance in the offspring; these findings were consistent with those of Garcia et al [ 164 ] who reported that phenotypic abnormality (weight gain and glucose intolerance) in the offspring might relate to the disruption of functionality of MAMs in oocytes following the oocyte-specific deletion of Mfn2.…”

Section: Mfns In Reproductive Diseasessupporting

confidence: 86%

“…During follicle and oocyte development, Mfn1 and Mfn2 have similar expression levels and are involved in maintaining normal follicular development via the regulation of mitochondrial membrane fusion, mitochondrial distribution, the activity of the OXPHOS complex subunits, and spindle function [ 126 , 127 ]. In mice, the abnormal aggregation of the mitochondria also disables the functionality of MAMs, thus leading to a reduction in mitochondrial OXPHOS and the Krebs cycle.…”

Section: Mfns In the Development Of Germ Cells And Embryosmentioning

confidence: 99%

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Mitofusins: from mitochondria to fertility

Zhao

Heng

Wang

et al. 2022

Cell. Mol. Life Sci.

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Germ cell formation and embryonic development require ATP synthesized by mitochondria. The dynamic system of the mitochondria, and in particular, the fusion of mitochondria, are essential for the generation of energy. Mitofusin1 and mitofusin2, the homologues of Fuzzy onions in yeast and Drosophila, are critical regulators of mitochondrial fusion in mammalian cells. Since their discovery mitofusins (Mfns) have been the source of significant interest as key influencers of mitochondrial dynamics, including membrane fusion, mitochondrial distribution, and the interaction with other organelles. Emerging evidence has revealed significant insight into the role of Mfns in germ cell formation and embryonic development, as well as the high incidence of reproductive diseases such as asthenospermia, polycystic ovary syndrome, and gestational diabetes mellitus. Here, we describe the key mechanisms of Mfns in mitochondrial dynamics, focusing particularly on the role of Mfns in the regulation of mammalian fertility, including spermatogenesis, oocyte maturation, and embryonic development. We also highlight the role of Mfns in certain diseases associated with the reproductive system and their potential as therapeutic targets.

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Section: Mfns In Reproductive Diseasessupporting

confidence: 86%

Section: Mfns In the Development Of Germ Cells And Embryosmentioning

confidence: 99%

Mitofusins: from mitochondria to fertility

Zhao

Heng

Wang

et al. 2022

Cell. Mol. Life Sci.

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“…In brief, PNMC exposure caused defective spindle stability and mitochondrial function. Given the close crosstalk between the spindle apparatus and mitochondria during meiotic maturation, we could not definitively conclude if the abnormal spindle instability resulted in mitochondrial dysfunction, or vice versa [45,46]. However, our findings directly validated that PNMC triggered early apoptosis in oocytes, likely due to mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 64%

3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial Dysfunction

Chen,

Luo,

et al. 2024

IJMS

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3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.

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“…Consistent with this, mammalian oocytes have an enriched mitochondrial DNA (mtDNA) copy number when compared to other somatic cells [ 32 ]. Oocyte viability has been linked to mitochondrial function, given the role of mitochondria in ATP production, metabolite supply and cell death regulation [ 33 ]. Furthermore, pathogenic changes to mitochondria lead to oxidative stress (OS) and elevated reactive oxygen species (ROS) [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency

Kline

Jaillard

Bell

et al. 2022

Genes

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The mitochondrial ribosome is critical to mitochondrial protein synthesis. Defects in both the large and small subunits of the mitochondrial ribosome can cause human disease, including, but not limited to, cardiomyopathy, hypoglycaemia, neurological dysfunction, sensorineural hearing loss and premature ovarian insufficiency (POI). POI is a common cause of infertility, characterised by elevated follicle-stimulating hormone and amenorrhea in women under the age of 40. Here we describe a patient with POI, sensorineural hearing loss and Hashimoto’s disease. The co-occurrence of POI with sensorineural hearing loss indicates Perrault syndrome. Whole exome sequencing identified two compound heterozygous variants in mitochondrial ribosomal protein 7 (MRPS7), c.373A>T/p.(Lys125*) and c.536G>A/p.(Arg179His). Both novel variants are predicted to be pathogenic via in-silico algorithms. Variants in MRPS7 have been described only once in the literature and were identified in sisters, one of whom presented with congenital sensorineural hearing loss and POI, consistent with our patient phenotype. The other affected sister had a more severe disease course and died in early adolescence due to liver and renal failure before the reproductive phenotype was known. This second independent report validates that variants in MRPS7 are a cause of syndromic POI/Perrault syndrome. We present this case and review the current evidence supporting the integral role of the mitochondrial ribosome in supporting ovarian function.

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Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission

Cited by 10 publications

References 181 publications

Mitofusins: from mitochondria to fertility

Mitofusins: from mitochondria to fertility

3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial Dysfunction

Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency

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