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Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging.

ABSTRACT: Mitochondria change their shape through fusion and fission in order to adapt to their metabolic milieu. Mitofusin-2 (MFN2) is a key regulatory protein in this process, mediating mitochondrial fusion and interaction with endoplasmic reticulum. Targeted deletion of Mfn2 in oocytes resulted in mitochondrial dysfunction and female subfertility associated with impaired oocyte maturation and follicle development. Oocytes lacking MFN2 showed shortened telomeres and increased apoptosis, resulting in compromised oocyte quality and accelerated follicular depletion, consistent with a reproductive aging phenotype.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6628992 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging.

Zhang Man M Bener Muhammed Burak MB Jiang Zongliang Z Wang Tianren T Esencan Ecem E Scott Richard R Horvath Tamas T Seli Emre E

Aging 20190601 12

Mitochondria change their shape through fusion and fission in order to adapt to their metabolic milieu. Mitofusin-2 (MFN2) is a key regulatory protein in this process, mediating mitochondrial fusion and interaction with endoplasmic reticulum. Targeted deletion of <i>Mfn2</i> in oocytes resulted in mitochondrial dysfunction and female subfertility associated with impaired oocyte maturation and follicle development. Oocytes lacking MFN2 showed shortened telomeres and increased apoptosis, resulting ...[more]

PMID: 31204316

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Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging

Project description:This SuperSeries is composed of the SubSeries listed below.

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Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging [GV]

Project description:We performed RNAseq analysis to determine the effect of MFN2 deletion on oocyte global gene expression profile. RNAseq revealed a total of 363 genes were significantly differentially expressed (p<0.05) in Mfn2-/- GV oocytes compared to WT (241 up-regulated and 122 down-regulated). Gene ontology (GO) analysis indicated significant over-representation of elements involved in regulation of embryonic development, cell death and survival, and cell morphology. Pathway analysis of top10 upregulated and downregulated annotated genes are listed. Our findings provide new insight into the role of MFN2 in the oocytes, and may help understand the potential mechanism of subfertility and reproductive aging associated with MFN2-deficiency.

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Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging [SFO]

Project description:We performed RNAseq analysis to determine the effect of MFN2 deletion on oocyte global gene expression profile. RNAseq revealed a total of 1041 genes were significantly differentially expressed (p<0.05) in Mfn2-/- seceondary follicle enclosed oocytes (SFOs) compared to WT, with 510 up-regulated and 531 down-regulated genes. GO cluster analysis indicated significant over-representation of elements involved in regulation of cell death and survival, cellular development and cellular growth. Pathway analysis of top10 upregulated and downregulated annotated genes are listed. Our findings provide new insight into the role of MFN2 in the oocytes, and may help understand the potential mechanism of subfertility and reproductive aging associated with MFN2-deficiency.

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Mitofusin 1 is required for female fertility and to maintain ovarian follicular reserve.

Project description:Mitochondria are dynamic organelles that continually adapt their structure through fusion and fission in response to changes in their bioenergetic environment. Targeted deletion of mitochondrial fusion protein mitofusin1 (MFN1) in oocytes resulted in female infertility associated with failure to achieve oocyte maturation. Oocyte-granulosa cell communication was impaired, and cadherins and connexins were downregulated, resulting in follicle developmental arrest at the secondary follicle stage. Deletion of MFN1 in oocytes resulted in mitochondrial dysfunction and altered mitochondrial dynamics, as well as accumulation of ceramide, which contributed to increased apoptosis and a reproductive phenotype that was partially rescued by treatment with ceramide synthesis inhibitor myriocin. Absence of MFN1 and resulting apoptotic cell loss also caused depletion of ovarian follicular reserve, and a phenotype consistent with accelerated female reproductive aging.

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Project description:Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging

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Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging [GV]

Project description:Mitofusin 2 is essential for oocyte and follicle development, and to maintain ovarian follicular reserve during reproductive aging [GV]

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Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre-implantation embryos.

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