Vertical transmission of maternal mitochondrial DNA through extracellular vesicles modulates embryo bioenergetics

Bolumar, David; Moncayo-Arlandi, Javier; González-Fernández, Javier; Ochando, Ana; Moreno, Inmaculada; Marín, Carlos; Dı́ez, A.; Fabra, Paula; Checa, Miguel Ángel; Espinós, Juan José; Simón, Carlos; Vilella, Felipe

doi:10.7554/elife.88008.1

Cited by 2 publications

(2 citation statements)

References 44 publications

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“…We observed 12 mitochondrial DEGs downregulated during the MS phase, which may help modify the endometrial tissue's energy production before embryo implantation. These changes may support the recently discovered mechanisms of vertical transmission of maternal mitochondrial DNA through extracellular vesicles from the endometrium to the embryo [26]. Moreover, a meaningful observation derived from the Hallmark enrichment analysis was the upregulation of hypoxia-related genes during the MS and LS phases of the menstrual cycle, likely indicating preparation for the upcoming tissue shedding and menstruation.…”

Section: Discussionsupporting

confidence: 70%

Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle

Apostolov,

Naydenov,

Kalinina

et al. 2024

IJMS

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The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcriptome-wide analyses have mainly been utilized to study endometrial receptivity, the prerequisite for successful implantation, with most studies, so far, comparing the endometrial transcriptomes between (i) secretory and proliferative endometrium or (ii) mid-secretory and early secretory endometrium. In the current study, we provide a complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points including the mid-proliferative, late proliferative (peri-ovulatory phase), early secretory, mid-secretory, and late secretory phases. Thus, we unveil exhaustively the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. The transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of coordinated gene activity, the expression profile of histone-encoding genes within the HIST cluster on chromosome 6 shows an increase in cluster activity during the late proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Our data analysis highlights significant transcriptomic and functional changes occurring during the late proliferative phase—an essential transition point from the proliferative phase to the secretory phase. Future studies should explore how the biology of the late proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.

show abstract

Section: Discussionsupporting

confidence: 70%

Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle

Apostolov,

Naydenov,

Kalinina

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…We observed 12 mitochondrial DEGs downregulated during the MS phase, which may help modify the endometrial tissue's energy production before embryo implantation. These changes may support the recently discovered mechanisms of vertical transmission of maternal mitochondrial DNA through extracellular vesicles from the endometrium to the embryo [33]. Moreover, a meaningful observation derived from the Hallmarks enrichment analysis was the upregulation of hypoxia-related genes during the MS and LS phases of the menstrual cycle, likely indicating the preparation for the upcoming tissue shedding and menstruation.…”

Section: Discussionsupporting

confidence: 69%

Endometrial Proliferative Phase-Centered View on the Transcriptome Dynamics Across the Menstrual Cycle

Apostolov,

Naydenov,

Kalinina

et al. 2024

Preprint

View full text Add to dashboard Cite

The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcrip-tome-wide analyses have mainly been utilized to study the endometrial receptivity, the prerequisite for successful implantation, with most of the studies, so far, comparing the endometrial transcriptomes between (i) secretory versus proliferative endometrium or (ii) mid-secretory versus early-secretory endometrium. In the current study, we provide the complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points: mid-proliferative, late-proliferative (peri-ovulatory phase), early-secretory, mid-secretory, and late-secretory phases. Thus, we exhaustively unveil the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. Transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of the coordinated gene activity, the expression profile of his-tone-encoding genes within the HIST cluster on chromosome 6 showed an increase in cluster activity during the late-proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Data analysis highlights significant transcriptomic and functional changes occurring during the late-proliferative phase – an essential transition point from the proliferative to the secretory phase. Future studies should explore how the biology of the late-proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.

show abstract

Vertical transmission of maternal mitochondrial DNA through extracellular vesicles modulates embryo bioenergetics

Cited by 2 publications

References 44 publications

Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle

Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle

Endometrial Proliferative Phase-Centered View on the Transcriptome Dynamics Across the Menstrual Cycle

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