Friday, May 9, 2025
5/9/2025
Cytoplasmic remodeling during the vertebrate oocyte-to-embryo transition - Project Summary/Abstract Reproduction is crucial for the survival of all species. Reproductive success can be influenced by genetic and environmental factors. In humans, at least 30% of infertile couples are diagnosed with unexplained infertility, arguing for the existence of novel mechanisms that are critically important for reproduction. The oocyte-to- embryo transition (OET) is crucial for reproduction. Prior to the OET, the oocyte accumulates large amounts of maternal products during oogenesis and is maintained in the ovary in a quiescent state. During the OET, the cellular organelles and maternal gene products stored in fully-grown oocytes are precisely remodeled to orchestrate the OET. Currently, the mechanisms responsible for these cytoplasmic remodeling events during the OET remain largely unclear. In an effort to study the cytoplasmic remodeling during Xenopus OET, we uncovered a novel function of the ER in controlling the localization of maternal mRNAs. We found that maternal RNAs are abundantly associated with the ER in the oocyte. After oocyte maturation, ER-associated mRNAs are released into the cytosol. The remodeling of the ER and decreased mRNA-ER association during oocyte maturation offer an important mechanism to sort maternal RNAs and correct localization errors that may have occurred during early oogenesis. It also contributes to the overall increase in protein synthesis rate after oocyte maturation. Furthermore, our preliminary results demonstrate that a subset of maternal mRNA undergoes phase transition during the OET. Based on these exciting findings, here we propose to test the hypothesis that dynamically regulated ER remodeling, mRNA-ER association, and RNA phase transition represent novel cytoplasmic remodeling mechanisms that are fundamentally important for vertebrate OET. To test this hypothesis, we propose 1) To determine the extent to which the remodeling of the ER, regulated mRNA-ER association, and RNA phase transition during the OET are evolutionarily conserved, 2) To investigate the role of the Cdc42-Wasl-Arp2/3 signaling cascade in regulating ER remodeling during the OET, and 3) To determine the extent to which exposure to an environmentally relevant phthalate mixture impairs cytoplasmic remodeling during the OET. The proposed work is expected to identify novel mechanisms that act during the OET to influence vertebrate reproductive success. This could have a major impact on improving human reproductive health.
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