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  • American Physiological Society  (4)
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  • American Physiological Society  (4)
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  • 1
    Online Resource
    Online Resource
    American Physiological Society ; 2019
    In:  American Journal of Physiology-Cell Physiology Vol. 317, No. 4 ( 2019-10-01), p. C655-C664
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 317, No. 4 ( 2019-10-01), p. C655-C664
    Abstract: Embryonic genome activation (EGA) in mammals begins with transient expression of a large group of genes (EGA1). Importantly, entry into and exit from the 2C/EGA state is essential for viability. Dux family member genes play an integral role in EGA1 by activating other EGA marker genes such as Zscan4 family members. We previously reported that structural maintenance of chromosomes flexible hinge domain-containing protein 1 ( Smchd1) is expressed at the mRNA and protein levels in mouse oocytes and early embryos and that elimination of Smchd1 expression inhibits inner cell mass formation, blastocyst formation and hatching, and term development. We extend these observations here by showing that siRNA knockdown of Smchd1 in zygotes results in overexpression of Dux and Zscan4 in two-cell embryos, with continued overexpression of Dux at least through the eight-cell stage as well as prolonged expression of Zscan4. These results are consistent with a role for SMCHD1 in promoting exit from the EGA1 state and establishing SMCHD1 as a maternal effect gene and the first chromatin regulatory factor identified with this role. Additionally, bioinformatics analysis reveals that SMCHD1 also contributes to the creation of a transcriptionally repressive state to allow correct gene regulation.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2019
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 2021
    In:  American Journal of Physiology-Cell Physiology Vol. 321, No. 6 ( 2021-12-01), p. C913-C931
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 321, No. 6 ( 2021-12-01), p. C913-C931
    Abstract: The morula-to-blastocyst transition (MBT) culminates with formation of inner cell mass (ICM) and trophectoderm (TE) lineages. Recent studies identified signaling pathways driving lineage specification, but some features of these pathways display significant species divergence. To better understand evolutionary conservation of the MBT, we completed a meta-analysis of RNA sequencing data from five model species and ICMTE differences from four species. Although many genes change in expression during the MBT within any given species, the number of shared differentially expressed genes (DEGs) is comparatively small, and the number of shared ICMTE DEGs is even smaller. DEGs related to known lineage determining pathways (e.g., POU5F1) are seen, but the most prominent pathways and functions associated with shared DEGs or shared across individual species DEG lists impact basic physiological and metabolic activities, such as TCA cycle, unfolded protein response, oxidative phosphorylation, sirtuin signaling, mitotic roles of polo-like kinases, NRF2-mediated oxidative stress, estrogen receptor signaling, apoptosis, necrosis, lipid and fatty acid metabolism, cholesterol biosynthesis, endocytosis, AMPK signaling, homeostasis, transcription, and cell death. We also observed prominent differences in transcriptome regulation between ungulates and nonungulates, particularly for ICM- and TE-enhanced mRNAs. These results extend our understanding of shared mechanisms of the MBT and formation of the ICM and TE and should better inform the selection of model species for particular applications.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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  • 3
    In: Physiological Genomics, American Physiological Society, Vol. 53, No. 4 ( 2021-04-01), p. 137-149
    Abstract: Oocyte maturation failure observed in assisted reproduction technology (ART) cycles can limit the number of quality oocytes obtained and present a pronounced barrier for some patients. The potential exists to use unmatured oocytes for ART through in vitro maturation. Understanding the molecular basis of oocyte maturation failure is pertinent to minimizing this loss of oocytes and considerations of whether such oocytes can be used safely for ART. We identified shared transcriptome abnormalities for rhesus monkey and human failed-to-mature (FTM) oocytes relative to healthy matured MII stage oocytes. We discovered that, although the number of shared affected genes was comparatively small, FTM oocytes in both species shared effects for several pathways and functions, including predicted activation of oxidative phosphorylation (OxPhos) with additional effects on mitochondrial function, lipid metabolism, transcription, nucleotide excision repair, endoplasmic reticulum stress, unfolded protein response, and cell viability. RICTOR emerged as a prominent upstream regulator with predicted inhibition across all analyses. Alterations in KDM5A, MTOR, MTORC1, INSR, CAB39L, and STK11 activities were implicated along with RICTOR in modulating mitochondrial activity and OxPhos. Defects in cell cycle progression were not a prominent feature of FTM oocytes. These results identify a common set of transcriptome abnormalities associated with oocyte maturation failure. While our results do not demonstrate causality, they indicate that fundamental aspects of cellular function are abnormal in FTM oocytes and raise significant concerns about the potential risks of using FTM oocytes for ART.
    Type of Medium: Online Resource
    ISSN: 1094-8341 , 1531-2267
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 2031330-5
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  • 4
    Online Resource
    Online Resource
    American Physiological Society ; 2021
    In:  American Journal of Physiology-Cell Physiology Vol. 321, No. 1 ( 2021-07-01), p. C3-C16
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 321, No. 1 ( 2021-07-01), p. C3-C16
    Abstract: Oogenesis is a complex process resulting in the production of a truly remarkable cell—the oocyte. Oocytes execute many unique processes and functions such as meiotic segregation of maternal genetic material, and essential life-generating functions after fertilization including posttranscriptional support of essential homeostatic and metabolic processes, and activation and reprogramming of the embryonic genome. An essential goal for understanding female fertility and infertility in mammals is to discover critical features driving the production of quality oocytes, particularly the complex regulation of oocyte maternal mRNAs. We report here the first in-depth meta-analysis of oocyte maturation-associated transcriptome changes, using eight datasets encompassing 94 RNAseq libraries for human, rhesus monkey, mouse, and cow. A majority of maternal mRNAs are regulated in a species-restricted manner, highlighting considerable divergence in oocyte transcriptome handling during maturation. We identified 121 mRNAs changing in relative abundance similarly across all four species (92 of high homology), and 993 (670 high homology) mRNAs regulated similarly in at least three of the four species, corresponding to just 0.84% and 6.9% of mRNAs analyzed. Ingenuity Pathway Analysis (IPA) revealed an association of these shared mRNAs with many shared pathways and functions, most prominently oxidative phosphorylation and mitochondrial function. These shared functions were reinforced further by primate-specific and species-specific differentially expressed genes (DEGs). Thus, correct downregulation of mRNAs related to oxidative phosphorylation and mitochondrial function is a major shared feature of mammalian oocyte maturation.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 1477334-X
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
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