The proteome, not the transcriptome, predicts that oocyte superovulation affects embryonic phenotypes in mice

Taher, Leila; Israel, Steffen; Drexler, Hannes C.A.; Makałowski, Wojciech; Suzuki, Yutaka; Fuellen, Georg; Boiani, Michele

doi:10.1038/s41598-021-03054-9

Cited by 11 publications

(16 citation statements)

References 107 publications

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“…To distinguish between the possibilities, we compared the synthesis of ZP proteins against the abundance of ZP transcripts. Although the transcription of ZP genes is oocyte-specific and >95% of ZP3 mRNA is reportedly degraded during ovulation 2,26 , reanalysis of our previously generated RNAseq data 18 revealed that the ZP transcripts are in fact not as scarce in embryos as previously assumed. At the blastocyst stage, for example, the ZP transcripts populated the median region of the transcriptome distribution (Figure 2A).…”

Section: Resultsmentioning

confidence: 64%

“… (a) . Genome-wide distribution of protein abundances (riBAQ) in zona-free oocytes, cleavage stages and blastocysts, based on the mass spectrometry dataset PXD012613 18 . The proteins ZP1, ZP2 and ZP3 populate, respectively, the 82 nd , 93 rd and 94 th percentile of the proteome distribution of oocytes, and the 80 th , 84 th and 84 th percentile of the proteome distribution of blastocysts.…”

Section: Resultsmentioning

confidence: 99%

“… (a) . Genome-wide distribution of transcript abundances (RPKM) in oocytes, cleavage stages and blastocysts, based on the dataset deposited in the DNA Databank of Japan Sequence Read Archive with the dataset identifier DRA005956 and DRA006335 18 . The mRNAs ZP1, ZP2 and ZP3 populate, respectively, the 97 th , 95 th and 97 th percentile of the transcriptome distribution of oocytes, and the 41 st , 46 th and 57 th percentile of the transcriptome distribution of blastocysts.…”

Section: Resultsmentioning

confidence: 99%

“…According to longstanding notion, the zona pellucida exclusively serves its functions outside the oocyte. We were therefore surprised to invariably find, in our previously generated mass spectrometric datasets [15][16][17][18][19] , conspicuous levels of the proteins ZP1, ZP2 and ZP3 in samples of preimplantation mouse embryos although these had been stripped of their zonae prior to lysis (Supplementary Figure S1). These levels were among the upper percentiles of the proteome abundance distribution 18 calculated using the 'intensity Based Absolute Quantification' algorithm 20 , which approximates the molar fraction of the proteins (Figure 1A).…”

Section: Zp Proteins Are Abundantly Present Inside Mouse Embryos Unti...mentioning

confidence: 99%

“…The unexpected finding of abundant intracellular ZP3 protein throughout preimplantation development was validated with immunoblotting and immunofluorescence using commercially available anti-ZP3 antibodies. A panel of not redundant anti-ZP3 antibodies (binding to different regions of the ZP3 protein) was screened, of which mouse monoclonal ATCC IE-10 CRL-2462, rabbit polyclonal Proteintech 21279-1-AP and Invitrogen PA5-89033 18,[21][22][23] (Figure 1B) were found to work better than others, recognizing a prominent band with ancillary bands of larger size in immunoblots of blastocyst lysates. This composite pattern is expected given the signal peptide and the glycosylation of ZP proteins, as noted in the Introduction.…”

Section: Zp Proteins Are Abundantly Present Inside Mouse Embryos Unti...mentioning

confidence: 99%

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Intracellular fraction of zona pellucida protein 3 is required for the oocyte to embryo transition in mice

Israel

Seyfarth

Nolte

et al. 2022

Preprint

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In oocyte biology the zona pellucida has long been known to operate three extracellular functions, namely, encasing the oocytes in ovarian follicles, mediating sperm-oocyte interaction and preventing premature embryo contact with maternal epithelia. The present study uncovers a fourth function that is fundamentally distinct from the other three, being critical for embryonic cell survival. Intriguingly, the three proteins of the mouse zona pellucida (ZP1, ZP2, ZP3) were found abundantly present also inside the embryo four days after fertilization, as shown by mass spectrometry, immunoblotting and immunofluorescence. Trim-away-mediated knockdown of ZPs in fertilized oocytes resulted in various grades of embryopathy: knockdown of ZP1 impeded blastocyst expansion, knockdown of ZP2 hampered the 2nd zygotic cleavage, while knockdown of ZP3 hampered the 1st zygotic cleavage - unlike the overexpression. Transcriptome analysis of ZP3-knockdown embryos pointed at defects of cytoplasmic translation in the context of embryonic genome activation. This conclusion was supported by reduced protein synthesis in the ZP3-knockdown and by the lack of cleavage arrest when knockdown was postponed from the 1-cell to the late 2-cell stage. These data place constraints on the long-standing notion that the zona pellucida proteins only operate in the extracellular space. We postulate that such noncanonical localization of ZP3 reflect novel roles in the interior of embryo during the oocyte-to-embryo transition in mice.

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Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Zp Proteins Are Abundantly Present Inside Mouse Embryos Unti...mentioning

confidence: 99%

Section: Zp Proteins Are Abundantly Present Inside Mouse Embryos Unti...mentioning

confidence: 99%

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Intracellular fraction of zona pellucida protein 3 is required for the oocyte to embryo transition in mice

Israel

Seyfarth

Nolte

et al. 2022

Preprint

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Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes

Cissé,

Montgomery,

Zierden

et al. 2023

Biology of Reproduction

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Entering pregnancy with a history of adversity, including adverse childhood experiences (ACEs) and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28–70 and were mated two weeks post-stress. MPS dams blunted the pregnancy-induced shift in the circulating extracellular vesicle proteome and reduced glucose tolerance at mid-gestation, suggesting a shift in pregnancy adaptation. To investigate MPS effects at the maternal:fetal interface, we probed the mid-gestation placental, uterine, and fetal brain tissue transcriptome. Male and female placentas differentially regulated expression of genes involved in growth and metabolic signaling in response to gestation in an MPS dam. We also report novel offspring sex- and MPS- specific responses in the uterine tissue apposing these placentas. In the fetal compartment, MPS female offspring reduced expression of neurodevelopmental genes. Using a ribosome-tagging transgenic approach we detected a dramatic increase in genes involved in chromatin regulation in a PVN enriched neuronal population in females at PN21. While MPS had an additive effect on high fat diet induced weight gain in male offspring, both MPS and high fat diet were necessary to induce significant weight gain in female offspring. These data highlight the preconception period as a determinant of maternal health in pregnancy and provides novel insights into mechanisms by which maternal stress history impacts offspring developmental programming.

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Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects

Ducreux,

Patrat,

Trasler

et al. 2023

Human Reproduction Update

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Background Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt. Objective and rationale The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART. Search methods An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues. Outcomes ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications. Wider implications Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it is likely that such dysregulations can be minimized by adapting ART protocols or reducing adverse exposure.

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The proteome, not the transcriptome, predicts that oocyte superovulation affects embryonic phenotypes in mice

Cited by 11 publications

References 107 publications

Intracellular fraction of zona pellucida protein 3 is required for the oocyte to embryo transition in mice

Intracellular fraction of zona pellucida protein 3 is required for the oocyte to embryo transition in mice

Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes

Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects

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