PXD059231

PXD059231 is an original dataset announced via ProteomeXchange.

Title	Depletion of MFF from oocytes impairs mitochondrial dynamics, leading to inhibited oocyte maturation and early embryonic development in mice
Description	Study question: To investigate the effect of mitochondrial fission factor (MFF) on oocyte competence and female fertility using an oocyte-specific Mff knockout mouse model. Summary answer: Oocyte-specific Mff deficiency hindered oocyte maturation and early embryonic development via regulation of mitochondrial dynamics, resulting in female subfertility. What is known already: Emerging studies have demonstrated that mitochondrial dynamics play a vital role in oocyte maturation and early embryo development. MFF is one of the crucial proteins regulating mitochondrial dynamics. Our previous studies have indicated that Mff is necessary for oocyte competence and fertility using a global Mff knockout mouse model. However, further investigation is needed to determine whether the deletion of Mff in oocytes could affect oocyte competence and early embryonic development by regulating mitochondrial dynamics. Study design, size, duration: The oocyte-specific Mff knockout (Mfffl/fl; Gdf9-Cre) mice were generated using the Cre-LoxP conditional knockout system. The 2-month-old female mice from each group (Mfffl/fl; Gdf9-Cre or Mfffl/fl, n=6) were mated to assess the fecundity over 10 months. The maturation and mitochondrial dynamics of germinal vesicle (GV) oocytes were determined. The spindle and chromosome morphologies of ovulated oocytes were also analyzed. Additionally, the 2-cell embryos were collected and cultured in vitro to assess early embryonic development. Participants/materials, setting, methods: Female mice from each group were mated with adult males to assess the fecundity. GV oocytes, ovulated oocytes, and 2-cell embryos were collected and cultured in vitro after superovulation, as indicated. Mitochondria, spindle, and chromosome were stained and then imaged using confocal microscopy. The microscopic morphology of mitochondria was assessed using electron microscopy. Main results and the role of chance: The Mfffl/fl; Gdf9-Cre mice consistently exhibited reduced fertility with a significant decrease in litter size (3.00 vs. 5.42, p<0.001), number of litters per female (4.33 vs. 7.50, p<0.001), and number of pups per female (13.00 vs. 40.67, p<0.001) compared to the Mfffl/fl mice. The numbers of GV oocytes (29.37 vs. 39.10, p<0.05), ovulated oocytes (9.81 vs. 20.91, p<0.001) and 2-cell embryos (3.50 vs. 10.17, p<0.05) were significantly lower in the Mfffl/fl; Gdf9-Cre mice. The blastocyst (32.32% vs. 68.44%, p<0.05) embryo development rate per 2-cell embryos was also significantly lower. In vitro maturation revealed that of Mfffl/fl; Gdf9-Cre GV oocytes had significantly lower rates of GV break-down (68.89% vs. 91.57%, p<0.05) and polar body extrusion (42.76% vs. 81.87%, p<0.05). The ratios of aberrant spindle (71.56% vs. 23.74%, p<0.001) and misaligned chromosomes (71.82% vs. 23.14%, p<0.01) in ovulated oocytes from Mfffl/fl; Gdf9-Cre mice were significantly increased. In terms of mitochondrial dynamics, the mitochondrial size (0.59 µm2 vs. 0.15 µm2, p<0.001) and the ratio (62.50% vs. 18.67%, p<0.01) of abnormal mitochondrial distribution (unevenly aggregated) in Mfffl/fl; Gdf9-Cre oocytes significantly elevated. This study found that the Mff played a crucial role in oocyte maturation and early embryonic development. Limitations, reasons for caution: Further research is needed to determine the downstream targets or pathways of Mff in oocytes. Wider implications of the findings: These results shed light on the important role played by MFF in ensuring proper mitochondrial dynamics in oocytes and underscore the significance of this protein in female fertility. This study provides insights into potential therapeutic targets for infertility and related diseases in humans.
HostingRepository	iProX
AnnounceDate	2024-12-25
AnnouncementXML	Submission_2026-01-04_00:37:42.454.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Renwu Hua
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-24 19:50:19	ID requested
⏵ 1	2026-01-04 00:37:43	announced

Dataset with its publication pending

submitter keyword: MFF

Oocyte maturation

conditional knockout

embryo development

Tianren Wang
contact affiliation	The University of Hongkong - Shenzhen Hospital
contact email	wtrcmu@126.com
lab head
Renwu Hua
contact affiliation	The University of Hongkong - Shenzhen Hospital
contact email	huarenwu1994@163.com
dataset submitter

iProX dataset URI