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The maternal to zygotic transition in mammals.

ABSTRACT: Prior to activation of the embryonic genome, the initiating events of mammalian development are under maternal control and include fertilization, the block to polyspermy and processing sperm DNA. Following gamete union, the transcriptionally inert sperm DNA is repackaged into the male pronucleus which fuses with the female pronucleus to form a 1-cell zygote. Embryonic transcription begins during the maternal to zygotic transfer of control in directing development. This transition occurs at species-specific times after one or several rounds of blastomere cleavage and is essential for normal development. However, even after activation of the embryonic genome, successful development relies on stored maternal components without which embryos fail to progress beyond initial cell divisions. Better understanding of the molecular basis of maternal to zygotic transition including fertilization, the activation of the embryonic genome and cleavage-stage development will provide insight into early human development that should translate into clinical applications for regenerative medicine and assisted reproductive technologies.

SUBMITTER: Li L

PROVIDER: S-EPMC3669654 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Project description:BackgroundRNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m5 C (5-methylcytosine)-coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m5 C modification is essential at multiple stages during the maternal-to-zygotic (MZT) transition.MethodsMouse ovaries and oocytes with Nsun5KO and the KGN cell line were subjected to m5 C identification, alternative splicing analysis and protein expression. BS-m5 C-seq, real-time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS-m5 C-seq revealed a dynamic pattern of m5 C sites and genes in the ovaries between Nsun5KO and WT mice at the 2-month and 6-month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5.ResultsHere, a maternal mRNA stability study showed that deletion of the m5 C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m5 C revealed that the level of m5 C decreased in a time-dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m5 C decline in the exon and 3'UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5KO triggers aberrant events in the exon region of Brd8.ConclusionsNsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m5 C-regulated maternal mRNA stabilization is essential for MZT transition.

Project description:Microarray analysis of zygotic gene expression in 2-to-3 hour wild-type (wt) and smg mutant embryos. Expression is relative to mature, stage 14 oocytes, which contain the full maternal pool of mRNA. Strictly maternal genes that are not transcribed at the MZT contribute approximately 80% of transcripts in early embryos, and are not shown. Class I zygotic genes showed high levels of expression in 2-to-3 hour embryos. 142 of the 166 Class I genes were not expressed in smg mutants. The remaining zygotically expressed genes were also present in oocytes. These genes were divided into two classes, based on analysis of 4-to-6 hour old unfertilized eggs (4-6h unf), which are transcriptionally inactive. Class-II genes produce maternal transcripts that are stable in unfertilized eggs and show significantly increased expression in 2-to-3 hour post-fertilization embryos. 358 of 395 Class-II genes require SMAUG for zygotic expression. Class-III genes produce maternal transcripts that are degraded in unfertilized eggs and show significantly increased expression in 2-to-3 hour post-fertilization embryos. 65 of 408 Class-III genes require SMAUG for expression in 2-to-3 hour embryos. mRNA was extracted from staged fertilized or unfertilized eggs, as well as stage 14 oocytes as described previously (Tadros et al., 2007a). To assay mRNA quality, known stable (rpA1) and unstable (Hsp83) transcripts were probed on Northern blots. Total RNA was then reverse transcribed with random primers (Tadros et al., 2007a) and labeled asÃ?described in the Indirect Labeling of Total RNA for Microarray Hybridization protocol at http://www.flyarrays.com. The fluorescently labeled cDNA probes were hybridized to 12Kv1 microarrays obtained from the Canadian Drosophila Microarray Centre (http://www.flyarrays.com; GEO platform accession number GPL1467: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL1467). Hybridization and scanning were performed using a PerkinElmer/GSI ScanArray 4000 scanner and the ScanArray software as previously described (Neal et al., 2003). The 16 bit TIFF image files were quantified using QuantArray Version 3 (PerkinElmer), using the adaptive quantification algorithm and analyzed using GeneTraffic Duo3.2 (Iobion Informatics/Stratagene). The 12Kv1 arrays were normalized using the rank invariant LOWESS extrapolation method (Schadt et al., 2001).

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The maternal to zygotic transition in mammals.

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