The degradation of maternally provided molecules is a very important process during early embryogenesis. However, the vast majority of studies deals with mRNA degradation and protein degradation is only a very little explored process yet. The aim of this article was to summarize current knowledge about the protein degradation during embryogenesis of mammals. In addition to resuming of known data concerning mammalian embryogenesis, we tried to fill the gaps in knowledge by comparison with facts known about protein degradation in early embryos of non-mammalian species. Maternal protein degradation seems to be driven by very strict rules in terms of specificity and timing. The degradation of some maternal proteins is certainly necessary for the normal course of embryonic genome activation (EGA) and several concrete proteins that need to be degraded before major EGA have been already found. Nevertheless, the most important period seems to take place even before preimplantation development-during oocyte maturation. The defects arisen during this period seems to be later irreparable.

Department of Veterinary Sciences Czech University of Life Sciences Prague Prague Czech Republic

Laboratory of Developmental Biology Institute of Animal Physiology and Genetics of the Czech Academy of Sciences Libechov Czech Republic

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Svoboda P, Fulka H, Malik R. Clearance of parental products. Adv Exp Med Biol. 2017;953:489–535. PubMed

Sha QQ, Zhang J, Fan HY. A story of birth and death: mRNA translation and clearance at the onset of maternal-to-zygotic transition in mammals. Biol Reprod. 2019;101:579–590. PubMed

Yokoi H, Natsuyama S, Iwai M, Noda Y, Mori T, Mori KJ, Fujita K, Nakayama H, Fujita J. Nonradioisotopic quantitative RT-PCR to detect changes in messenger-RNA levels during early mouse embryo development. Biochem Biophys Res Commun. 1993;195:769–775. PubMed

Karabinova P, Kubelka M, Susor A. Proteasomal degradation of ubiquitinated proteins in oocyte meiosis and fertilization in mammals. Cell Tissue Res. 2011;346:1–9. PubMed

Shin SW, Tokoro M, Nishikawa S, Lee HH, Hatanaka Y, Nishihara T, Amano T, Anzai M, Kato H, Mitani T, et al. Inhibition of the ubiquitin–proteasome system leads to delay of the onset of ZGA gene expression. J Reprod Dev. 2010;56:655–663. PubMed

Chalupnikova K, Solc P, Sulimenko V, Sedlacek R, Svoboda P. An oocyte-specific ELAVL2 isoform is a translational repressor ablated from meiotically competent antral oocytes. Cell Cycle. 2014;13:1187–1200. PubMed PMC

Huo LJ, Zhong ZS, Liang CG, Wang Q, Yin S, Ai JS, Yu LZ, Chen DY, Schatten H, Sun QY. Degradation of securin in mouse and pig oocytes is dependent on ubiquitin–proteasome pathway and is required for proteolysis of the cohesion subunit, Rec8, at the metaphase-to-anaphase transition. Front Biosci. 2006;11:2193–2202. PubMed

Bachvarova R. Synthesis, turnover, and stability of heterogeneous RNA in growing mouse oocytes. Dev Biol. 1981;86:384–392. PubMed

Sun L, Bertke MM, Champion MM, Zhu G, Huber PW, Dovichi NJ. Quantitative proteomics of Xenopus laevis embryos: expression kinetics of nearly 4000 proteins during early development. Sci Rep. 2014;4:4365. PubMed PMC

Henderson GRW, Brahmasani SR, Yelisetti UM, Konijeti S, Katari VC, Sisinthy S. Candidate gene expression patterns in rabbit preimplantation embryos developed in vivo and in vitro. J Assist Reprod Genet. 2014;31:899–911. PubMed PMC

Lee G, Hynes R, Kirschner M. Temporal and spatial regulation of fibronectin in early Xenopus development. Cell. 1984;36:729–740. PubMed

Jansova D, Tetkova A, Koncicka M, Kubelka M, Susor A. Localization of RNA and translation in the mammalian oocyte and embryo. PLoS ONE. 2018;13:e0192544. PubMed PMC

Tetkova A, Jansova D, Susor A. Spatio-temporal expression of ANK2 promotes cytokinesis in oocytes. Sci Rep. 2019;9:13121. PubMed PMC

Liu B, Winkler F, Herde M, Witte CP, Großhans J. A link between deoxyribonucleotide metabolites and embryonic cell-cycle control. Curr Biol. 2019;29:1187–1192. PubMed

Djabrayan NJV, Smits CM, Krajnc M, Stern T, Yamada S, Lemon WC, Keller PJ, Rushlow CA, Shvartsman SY. Metabolic regulation of developmental cell cycles and zygotic transcription. Curr Biol. 2019;29:1193–1198. PubMed PMC

Nagaraj R, Sharpley MS, Chi F, Braas D, Zhou Y, Kim R, Clark AT, Banerjee U. Nuclear localization of mitochondrial TCA cycle enzymes as a critical step in mammalian zygotic genome activation. Cell. 2017;168:210–223. PubMed PMC

Gilbert SF. Developmental biology. 6. Sunderland: Sinauer Associates; 2000.

Tomanek M, Kopecny V, Kanka J. Genome reactivation in developing early pig embryos: an ultrastructural and autoradiographic analysis. Anat Embryol (Berl) 1989;180:309–316. PubMed

Kanka J. Gene expression and chromatin structure in the pre-implantation embryo. Theriogenology. 2003;59:3–19. PubMed

Kanka J, Bryova A, Duranthon V, Oudin JF, Peynot N, Renard JP. Identification of differentially expressed mRNAs in bovine preimplantation embryos. Zygote. 2003;11:43–52. PubMed

Johnson MH, Ziomek CA. The foundation of two distinct cell lineages within the mouse morula. Cell. 1981;24:71–80. PubMed

Johnson MH, Ziomek CA. Induction of polarity in mouse 8-cell blastomeres: specificity, geometry, and stability. J Cell Biol. 1981;91:303–308. PubMed PMC

Hiiragi T, Solter D. First cleavage plane of the mouse egg is not predetermined but defined by the topology of the two apposing pronuclei. Nature. 2004;430:360–364. PubMed

Motosugi N, Bauer T, Polanski Z, Solter D, Hiiragi T. Polarity of the mouse embryo is established at blastocyst and is not prepatterned. Genes Dev. 2005;19:1081–1092. PubMed PMC

Wennekamp S, Mesecke S, Nédélec F, Hiiragi T. A self-organization framework for symmetry breaking in the mammalian embryo. Nat Rev Mol Cell Biol. 2013;14:452–459. PubMed

Lund E, Sheets MD, Imboden SB, Dahlberg JE. Limiting Ago protein restricts RNAi and microRNA biogenesis during early development in Xenopus laevis. Genes Dev. 2011;25:1121–1131. PubMed PMC

Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82:373–428. PubMed

Fuchs O. The role of ubiquitin–proteasome system in transforming growth factor-β signaling and its importance in tumorigenesis. Klin Onkol. 2005;18:199–206.

Muratani M, Tansey WP. How the ubiquitin–proteasome system controls transcription. Nat Rev Mol Cell Biol. 2003;4:192–201. PubMed

Osley MA. H2B ubiquitylation: the end is in sight. Biochim Biophys Acta. 2004;1677:74–78. PubMed

Lipford JR, Smith GT, Chi Y, Deshaies RJ. A putative stimulatory role for activator turnover in gene expression. Nature. 2005;438:113–116. PubMed

Gillette TG, Gonzalez F, Delahodde A, Johnston SA, Kodadek T. Physical and functional association of RNA polymerase II and the proteasome. Proc Natl Acad Sci USA. 2004;101:5904–5909. PubMed PMC

Mukhopadhyay D, Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science. 2007;315:201–205. PubMed

DeRenzo C, Seydoux G. A clean start: degradation of maternal proteins at the oocyte-to-embryo transition. Trends Cell Biol. 2004;14:420–426. PubMed

Mtango NR, Latham KE. Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and embryos of different developmental potential. Physiol Genom. 2007;31:1–14. PubMed

Verlhac MH, Terret ME, Pintard L. Control of the oocyte-to-embryo transition by the ubiquitin–proteolytic system in mouse and C. elegans. Curr Opin Cell Biol. 2010;22:758–763. PubMed

Suzumori N, Burns KH, Yan W, Matzuk MM. RFPL4 interacts with oocyte proteins of the ubiquitin–proteasome degradation pathway. Proc Natl Acad Sci USA. 2003;100:550–555. PubMed PMC

Yang Y, Zhou C, Wang Y, Liu W, Liu C, Wang L, Liu Y, Shang Y, Li M, Zhou S, et al. The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for maternal-to-zygotic transition. EMBO Rep. 2017;18:205–216. PubMed PMC

Wang S, Kou Z, Jing Z, Zhang Y, Guo X, Dong M, Wilmut I, Gao S. Proteome of mouse oocytes at different developmental stages. Proc Natl Acad Sci USA. 2010;107:17639–17644. PubMed PMC

Zhang P, Ni X, Guo Y, Guo X, Wang Y, Zhou Z, Huo R, Sha J. Proteomic-based identification of maternal proteins in mature mouse oocytes. BMC Genom. 2009;10:348. PubMed PMC

Livneh I, Cohen-Kaplan V, Cohen-Rosenzweig C, Avni N, Ciechanover A. The life cycle of the 26S proteasome: from birth, through regulation and function, and onto its death. Cell Res. 2016;26:869–885. PubMed PMC

Meiners S, Heyken D, Weller A, Ludwig A, Stangl K, Kloetzel PM, Krüger E. Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of Mammalian proteasomes. J Biol Chem. 2003;278:21517–21525. PubMed

Potireddy S, Vassena R, Patel BG, Latham KE. Analysis of polysomal mRNA populations of mouse oocytes and zygotes: dynamic changes in maternal mRNA utilization and function. Dev Biol. 2006;298:155–166. PubMed

Graf A, Krebs S, Heininen-Brown M, Zakhartchenko V, Blum H, Wolf E. Genome activation in bovine embryos: review of the literature and new insights from RNA sequencing experiments. Anim Reprod Sci. 2014;149:46–58. PubMed

Benesova V, Kinterova V, Kanka J, Toralova T. Characterization of SCF-complex during bovine preimplantation development. PLoS ONE. 2016;11:e0147096. PubMed PMC

Shin SW, Shimizu N, Tokoro M, Nishikawa S, Hatanaka Y, Anzai M, Hamazaki J, Kishigami S, Saeki K, Hosoi Y, et al. Mouse zygote-specific proteasome assembly chaperone important for maternal-to-zygotic transition. Biol Open. 2013;2:170–182. PubMed PMC

Wójcik C, Benchaib M, Lornage J, Czyba JC, Guerin JF. Localization of proteasomes in human oocytes and preimplantation embryos. Mol Hum Reprod. 2000;6:331–336. PubMed

Evsikov AV, de Vries WN, Peaston AE, Radford EE, Fancher KS, Chen FH, Blake JA, Bult CJ, Latham KE, Solter D, Knowles BB. Systems biology of the 2-cell mouse embryo. Cytogenet Genome Res. 2004;105:240–250. PubMed

Huo LJ, Fan HY, Zhong ZS, Chen DY, Schatten H, Sun QY. Ubiquitin–proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation. Mech Dev. 2004;121:1275–1287. PubMed

Kepkova KV, Vodicka P, Toralova T, Lopatarova M, Cech S, Dolezel R, Havlicek V, Besenfelder U, Kuzmany A, Sirard MA, Laurincik J, Kanka J. Transcriptomic analysis of in vivo and in vitro produced bovine embryos revealed a developmental change in cullin 1 expression during maternal-to-embryonic transition. Theriogenology. 2011;75:1582–1595. PubMed

Sutovsky P, Motlik J, Neuber E, Pavlok A, Schatten G, Palecek J, Hyttel P, Adebayo OT, Adwan K, Alberio R, et al. Accumulation of the proteolytic marker peptide ubiquitin in the trophoblast of mammalian blastocysts. Cloning Stem Cells. 2001;3:157–161. PubMed

Baek KH, Lee H, Yang S, Lim SB, Lee W, Lee JE, Lim JJ, Jun K, Lee DR, Chung Y. Embryonic demise caused by targeted disruption of a cysteine protease Dub-2. PLoS ONE. 2012;7:e44223. PubMed PMC

Lu H, Shamanna RA, de Freitas JK, Okur M, Khadka P, Kulikowicz T, Holland PP, Tian J, Croteau DL, Davis AJ, et al. Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nat Commun. 2017;8:2039. PubMed PMC

Yin J, Kwon YT, Varshavsky A, Wang W. RECQL4, mutated in the Rothmund–Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway. Hum Mol Genet. 2004;13:2421–2430. PubMed

Larsen CN, Krantz BA, Wilkinson KD. Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry. 1998;37:3358–3368. PubMed

Amerik AY, Hochstrasser M. Mechanism and function of deubiquitinating enzymes. Biochim Biophys Acta. 2004;1695:189–207. PubMed

Wilkinson KD. DUBs at a glance. J Cell Sci. 2009;122:2325–2329. PubMed PMC

Susor A, Liskova L, Toralova T, Pavlok A, Pivonkova K, Karabinova P, Lopatarova M, Sutovsky P, Kubelka M. Role of ubiquitin C-terminal hydrolase-L1 in antipolyspermy defense of mammalian oocytes. Biol Reprod. 2010;82:1151–1161. PubMed

Fraile JM, Campos-Iglesias D, Rodríguez F, Astudillo A, Vilarrasa-Blasi R, Verdaguer-Dot N, Prado MA, Paulo JA, Gygi SP, Martín-Subero JI, et al. Loss of the deubiquitinase USP36 destabilizes the RNA helicase DHX33 and causes preimplantation lethality in mice. J Biol Chem. 2018;293:2183–2194. PubMed PMC

Mtango NR, Latham KE, Sutovsky P. Deubiquitinating enzymes in oocyte maturation, fertilization and preimplantation embryo development. Adv Exp Med Biol. 2014;759:89–110. PubMed

Ellederova Z, Halada P, Man P, Kubelka M, Motlik J, Kovarova H. Protein patterns of pig oocytes during in vitro maturation. Biol Reprod. 2004;71:1533–1539. PubMed

Massicotte L, Coenen K, Mourot M, Sirard MA. Maternal housekeeping proteins translated during bovine oocyte maturation and early embryo development. Proteomics. 2006;6:3811–3820. PubMed

Koyanagi S, Hamasaki H, Sekiguchi S, Hara K, Ishii Y, Kyuwa S, Yoshikawa Y. Effects of ubiquitin C-terminal hydrolase L1 deficiency on mouse ova. Reproduction. 2012;143:271–279. PubMed

Mtango NR, Sutovsky M, VandeVoort CA, Latham KE, Sutovsky P. Essential role of ubiquitin C-terminal hydrolases UCHL1 and UCHL3 in mammalian oocyte maturation. J Cell Physiol. 2012;227:2022–2029. PubMed PMC

Scheuermann JC, Gutiérrez L, Müller J. Histone H2A monoubiquitination and Polycomb repression: the missing pieces of the puzzle. Fly (Austin) 2012;6:162–168. PubMed

Liu C, Ma Y, Shang Y, Huo R, Li W. Post-translational regulation of the maternal-to-zygotic transition. Cell Mol Life Sci CMLS. 2018;75:1707–1722. PubMed PMC

Shimizu N, Ueno K, Kurita E, Shin SW, Nishihara T, Amano T, Anzai M, Kishigami S, Kato H, Mitani T, Hosoi Y, et al. Possible role of ZPAC, zygote-specific proteasome assembly chaperone, during spermatogenesis in the mouse. J Reprod Dev. 2014;60:179–186. PubMed PMC

Ramos PC, Dohmen RJ. PACemakers of proteasome core particle assembly. Structure. 2008;16:1296–1304. PubMed

Zuo EW, Yang XG, Lu YQ, Xie L, Shang JH, Li D, Yang H, Hu LL, Zhao HM, Lu SS, et al. ZPAC is required for normal spermatogenesis in mice. Mol Reprod Dev. 2015;82:747–755. PubMed

Bosu DR, Kipreos ET. Cullin-RING ubiquitin ligases: global regulation and activation cycles. Cell Div. 2008;3:7. PubMed PMC

Zhou L, Zhang W, Sun Y, Jia L. Protein neddylation and its alterations in human cancers for targeted therapy. Cell Signal. 2018;44:92–102. PubMed PMC

Yu C, Zhang YL, Pan WW, Li XM, Wang ZW, Ge ZJ, Zhou JJ, Cang Y, Tong C, Sun QY, Fan HY. CRL4 complex regulates mammalian oocyte survival and reprogramming by activation of TET proteins. Science. 2013;342:1518–1521. PubMed

Xu YW, Cao LR, Wang M, Xu Y, Wu X, Liu J, Tong C, Fan HY. Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice. J Cell Sci. 2017;130:3297–3307. PubMed

Zhang YL, Zhao LW, Zhang J, Le R, Ji SY, Chen C, Gao Y, Li D, Gao S, Fan HY. DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development. EMBO J. 2018;37:e9898. PubMed PMC

Zhang J, Zhang YL, Zhao LW, Guo JX, Yu JL, Ji SY, Cao LR, Zhang SY, Shen L, Ou XH, Fan HY. Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance and oocyte growth by mediating rRNA processing. Cell Death Differ. 2019;26:1251–1266. PubMed PMC

Liu Y, Zhao LW, Shen JL, Fan HY, Jin Y. Maternal DCAF13 regulates chromatin tightness to contribute to embryonic development. Sci Rep. 2019;9:6278. PubMed PMC

Kinterova V, Kanka J, Petruskova V, Toralova T. Inhibition of Skp1-Cullin-F-box complexes during bovine oocyte maturation and preimplantation development leads to delayed development of embryos. Biol Reprod. 2019;100:896–906. PubMed

Chen J, Melton C, Suh N, Oh JS, Horner K, Xie F, Sette C, Blelloch R, Conti M. Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition. Genes Dev. 2011;25:755–766. PubMed PMC

Sousa Martins JP, Liu X, Oke A, Arora R, Franciosi F, Viville S, Laird DJ, Fung JC, Conti M. DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation. J Cell Sci. 2016;129:1271–1282. PubMed PMC

Setoyama D, Yamashita M, Sagata N. Mechanism of degradation of CPEB during Xenopus oocyte maturation. Proc Natl Acad Sci USA. 2007;104:18001–18006. PubMed PMC

Shimuta K, Nakajo N, Uto K, Hayano Y, Okazaki K, Sagata N. Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition. EMBO J. 2002;21:3694–3703. PubMed PMC

Kanemori Y, Uto K, Sagata N. Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proc Natl Acad Sci USA. 2005;102:6279–6284. PubMed PMC

Collart C, Smith JC, Zegerman P. Chk1 inhibition of the replication factor Drf1 guarantees cell-cycle elongation at the Xenopus laevis mid-blastula transition. Dev Cell. 2017;42:82–96.e3. PubMed PMC

Daldello EM, Le T, Poulhe R, Jessus C, Haccard O, Dupré A. Control of Cdc6 accumulation by Cdk1 and MAPK is essential for completion of oocyte meiotic divisions in Xenopus. J Cell Sci. 2015;128:2482–2496. PubMed

Yu C, Ji SY, Sha QQ, Sun QY, Fan HY. CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. Nat Commun. 2015;6:8017. PubMed PMC

Ooga M, Suzuki MG, Aoki F. Involvement of histone H2B monoubiquitination in the regulation of mouse preimplantation development. J Reprod Dev. 2015;61:179–184. PubMed PMC

Jin XL, Chandrakanthan V, Morgan HD, O’Neill C. Preimplantation embryo development in the mouse requires the latency of TRP53 expression, which is induced by a ligand-activated PI3 kinase/AKT/MDM2-mediated signaling pathway. Biol Reprod. 2009;80:286–294. PubMed PMC

Jones SN, Roe AE, Donehower LA, Bradley A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature. 1995;378:206–208. PubMed

de Oca M, Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature. 1995;378:203–206. PubMed

Baran V, Brzakova A, Rehak P, Kovarikova V, Solc P. PLK1 regulates spindle formation kinetics and APC/C activation in mouse zygote. Zygote. 2016;24:338–345. PubMed

Solc P, Kitajima TS, Yoshida S, Brzakova A, Kaido M, Baran V, Mayer A, Samalova P, Motlik J, Ellenberg J. Multiple requirements of PLK1 during mouse oocyte maturation. PLoS ONE. 2015;10:e0116783. PubMed PMC

Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol. 2007;8:379–393. PubMed

Roest HP, Baarends WM, de Wit J, van Klaveren JW, Wassenaar E, Hoogerbrugge JW, van Cappellen WA, Hoeijmakers JHJ, Grootegoed JA. The ubiquitin-conjugating DNA repair enzyme HR6A is a maternal factor essential for early embryonic development in mice. Mol Cell Biol. 2004;24:5485–5495. PubMed PMC

Xu YN, Shen XH, Lee SE, Kwon JS, Kim DJ, Heo YT, Cui XS, Kim NH. Autophagy influences maternal mRNA degradation and apoptosis in porcine parthenotes developing in vitro. J Reprod Dev. 2012;58:576–584. PubMed

Shen X, Zhang N, Wang Z, Bai G, Zheng Z, Gu Y, Wu Y, Liu H, Zhou D, Lei L. Induction of autophagy improves embryo viability in cloned mouse embryos. Sci Rep. 2015;5:17829. PubMed PMC

Chi D, Zeng Y, Xu M, Si L, Qu X, Liu H, Li J. LC3-dependent autophagy in Pig 2-cell cloned embryos could influence the degradation of maternal mRNA and the regulation of epigenetic modification. Cell Reprogramming. 2017;19:354–362. PubMed

Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321:117–120. PubMed

He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009;43:67–93. PubMed PMC

Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147:728–741. PubMed

Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 2003;100:15077–15082. PubMed PMC

Lee SE, Hwang KC, Sun SC, Xu YN, Kim NH. Modulation of autophagy influences development and apoptosis in mouse embryos developing in vitro. Mol Reprod Dev. 2011;78:498–509. PubMed

Cho YH, Han KM, Kim D, Lee J, Lee SH, Choi KW, Kim J, Han YM. Autophagy regulates homeostasis of pluripotency-associated proteins in hESCs. Stem Cells. 2014;32:424–435. PubMed

Tsukamoto S, Tatsumi T. Degradation of maternal factors during preimplantation embryonic development. J Reprod Dev. 2018;64:217–222. PubMed PMC

Yamamoto A, Mizushima N, Tsukamoto S. Fertilization-induced autophagy in mouse embryos is independent of mTORC1. Biol Reprod. 2014;91:7. PubMed

Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122:3589–3594. PubMed PMC

Imamura T, Neildez TMA, Thenevin C, Paldi A. Essential role for poly(ADP-ribosyl)ation in mouse preimplantation development. BMC Mol Biol. 2004;5:4. PubMed PMC

Lee HR, Gupta MK, Kim DH, Hwang JH, Kwon B, Lee HT. Poly(ADP-ribosyl)ation is involved in pro-survival autophagy in porcine blastocysts. Mol Reprod Dev. 2016;83:37–49. PubMed

Lee JE, Oh HA, Song H, Jun JH, Roh CR, Xie H, Dey SK, Lim HJ. Autophagy regulates embryonic survival during delayed implantation. Endocrinology. 2011;152:2067–2075. PubMed

Tsukamoto S, Hara T, Yamamoto A, Kito S, Minami N, Kubota T, Sato K, Kokubo T. Fluorescence-based visualization of autophagic activity predicts mouse embryo viability. Sci Rep. 2014;4:4533. PubMed PMC

Lee HR, Kim DH, Kim MG, Lee JS, Hwang JH, Lee HT. The regulation of autophagy in porcine blastocysts: regulation of PARylation-mediated autophagy via mammalian target of rapamycin complex 1 (mTORC1) signaling. Biochem Biophys Res Commun. 2016;473:899–906. PubMed

Song BS, Yoon SB, Kim JS, Sim BW, Kim YH, Cha JJ, Choi SA, Min HK, Lee Y, Huh JW, et al. Induction of autophagy promotes preattachment development of bovine embryos by reducing endoplasmic reticulum stress. Biol Reprod. 2012;87:1–11. PubMed

Xu YN, Cui XS, Sun SC, Lee SE, Li YH, Kwon JS, Lee SH, Hwang KC, Kim NH. Mitochondrial dysfunction influences apoptosis and autophagy in porcine parthenotes developing in vitro. J Reprod Dev. 2011;57:143–150. PubMed

Kang MH, Das J, Gurunathan S, Park HW, Song H, Park C, Kim JH. The cytotoxic effects of dimethyl sulfoxide in mouse preimplantation embryos: a mechanistic study. Theranostics. 2017;7:4735–4752. PubMed PMC

Shin KT, Guo J, Niu YJ, Cui XS. The toxic effect of aflatoxin B1 on early porcine embryonic development. Theriogenology. 2018;118:157–163. PubMed

Tang L, Yang S, Wang H, Gu H, Xia X, Feng Y, Yang Z, Zhao S, Su C, Su Z, et al. Nucleoside reverse transcriptase inhibitor-induced rat oocyte dysfunction and low fertility mediated by autophagy. Oncotarget. 2018;9:3895–3907. PubMed PMC

Lin T, Oqani RK, Lee JE, Kang JW, Kim SY, Cho ES, Jeong YD, Baek JJ, Jin DI. α-Solanine impairs oocyte maturation and quality by inducing autophagy and apoptosis and changing histone modifications in a pig model. Reprod Toxicol. 2018;75:96–109. PubMed

Sutovsky P, Manandhar G, Laurincik J, Letko J, Caamaño JN, Day BN, Lai L, Prather RS, Sharpe-Timms KL, Zimmer R, et al. Expression and proteasomal degradation of the major vault protein (MVP) in mammalian oocytes and zygotes. Reproduction. 2005;129:269–282. PubMed

Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. Recognition of the polyubiquitin proteolytic signal. EMBO J. 2000;19:94–102. PubMed PMC

Tan JMM, Wong ESP, Kirkpatrick DS, Pletnikova O, Ko HS, Tay SP, Ho MWL, Troncoso J, Gygi SP, Lee MK, et al. Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases. Hum Mol Genet. 2008;17:431–439. PubMed

Sato M, Konuma R, Sato K, Tomura K, Sato K. Fertilization-induced K63-linked ubiquitylation mediates clearance of maternal membrane proteins. Development. 2014;141:1324–1331. PubMed

Rojansky R, Cha MY, Chan DC. Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. eLife. 2016;5:e17896. PubMed PMC

Hajjar C, Sampuda KM, Boyd L. Dual roles for ubiquitination in the processing of sperm organelles after fertilization. BMC Dev Biol. 2014;14:6. PubMed PMC

Song WH, Yi YJ, Sutovsky M, Meyers S, Sutovsky P. Autophagy and ubiquitin–proteasome system contribute to sperm mitophagy after mammalian fertilization. Proc Natl Acad Sci USA. 2016;113:E5261–5270. PubMed PMC

Komatsu M, Ichimura Y. Selective autophagy regulates various cellular functions. Genes Cells Devoted Mol Cell Mech. 2010;15:923–933. PubMed

Benesova V, Kinterova V, Kanka J, Toralova T. Potential involvement of SCF-complex in zygotic genome activation during early bovine embryo development. Methods Mol Biol. 2017;1605:245–257. PubMed

Hanson PI, Cashikar A. Multivesicular body morphogenesis. Annu Rev Cell Dev Biol. 2012;28:337–362. PubMed

Traub LM, Lukacs GL. Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs. J Cell Sci. 2007;120:543–553. PubMed

Sato M, Sato K. Dynamic regulation of autophagy and endocytosis for cell remodeling during early development. Traffic. 2013;14:479–486. PubMed

Sato K, Sato M, Audhya A, Oegema K, Schweinsberg P, Grant BD. Dynamic regulation of caveolin-1 trafficking in the germ line and embryo of Caenorhabditis elegans. Mol Biol Cell. 2006;17:3085–3094. PubMed PMC

Balklava Z, Pant S, Fares H, Grant BD. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nat Cell Biol. 2007;9:1066–1073. PubMed

Kadandale P, Stewart-Michaelis A, Gordon S, Rubin J, Klancer R, Schweinsberg P, Grant BD, Singson A. The egg surface LDL receptor repeat-containing proteins EGG-1 and EGG-2 are required for fertilization in Caenorhabditis elegans. Curr Biol. 2005;15:2222–2229. PubMed

Audhya A, McLeod IX, Yates JRIII, Oegema K. MVB-12, a Fourth subunit of metazoan ESCRT-I, functions in receptor downregulation. PLoS ONE. 2007;2:9. PubMed PMC

Zuo Y, Su G, Wang S, Yang L, Liao M, Wei Z, Bai C, Li G. Exploring timing activation of functional pathway based on differential co-expression analysis in preimplantation embryogenesis. Oncotarget. 2016;7:74120–74131. PubMed PMC

Miller-Fleming L, Olin-Sandoval V, Campbell C, Ralser M. Remaining mysteries of molecular biology: the role of polyamines in the cell. J Mol Biol. 2015;427:3389–3406. PubMed

Fenelon JC, Murphy BD. Inhibition of polyamine synthesis causes entry of the mouse blastocyst into embryonic diapause. Biol Reprod. 2017;97:119–132. PubMed

Lenis YY, Johnson GA, Wang X, Tang WW, Dunlap KA, Satterfield MC, Wu G, Hansen TR, Bazer FW. Functional roles of ornithine decarboxylase and arginine decarboxylase during the peri-implantation period of pregnancy in sheep. J Anim Sci Biotechnol. 2018;9:10. PubMed PMC

Pendeville H, Carpino N, Marine JC, Takahashi Y, Muller M, Martial JA, Cleveland JL. The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol Cell Biol. 2001;21:6549–6558. PubMed PMC

Pegg AE. Regulation of ornithine decarboxylase. J Biol Chem. 2006;281:14529–14532. PubMed

Osborne HB, Duval C, Ghoda L, Omilli F, Bassez T, Coffino P. Expression and post-transcriptional regulation of ornithine decarboxylase during early Xenopus development. Eur J Biochem. 1991;202:575–581. PubMed

Reverte CG, Ahearn MD, Hake LE. CPEB degradation during Xenopus oocyte maturation requires a PEST domain and the 26S proteasome. Dev Biol. 2001;231:447–458. PubMed

Mendez R, Barnard D, Richter JD. Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction. EMBO J. 2002;21:1833–1844. PubMed PMC

Hodgman R, Tay J, Mendez R, Richter JD. CPEB phosphorylation and cytoplasmic polyadenylation are catalyzed by the kinase IAK1/Eg2 in maturing mouse oocytes. Development. 2001;128:2815–2822. PubMed

Uzbekova S, Arlot-Bonnemains Y, Dupont J, Dalbiès-Tran R, Papillier P, Pennetier S, Thélie A, Perreau C, Mermillod P, Prigent C, et al. Spatio-temporal expression patterns of aurora kinases A, B, and C and cytoplasmic polyadenylation-element-binding protein in bovine oocytes during meiotic maturation. Biol Reprod. 2008;78:218–233. PubMed

Bowerman B, Kurz T. Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during early C. elegans embryogenesis. Development. 2006;133:773–784. PubMed

Kurz T, Pintard L, Willis JH, Hamill DR, Gönczy P, Peter M, Bowerman B. Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Science. 2002;295:1294–1298. PubMed

Furukawa M, He YJ, Borchers C, Xiong Y. Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat Cell Biol. 2003;5:1001–1007. PubMed

Gao S, Han Z, Kihara M, Adashi E, Latham EK. Protease inhibitor MG132 in cloning: no end to the nightmare. Trends Biotechnol. 2005;23:66–68. PubMed

Yu Y, Yong J, Li X, Qing T, Qin H, Xiong X, You J, Ding M, Deng H. The proteasomal inhibitor MG132 increases the efficiency of mouse embryo production after cloning by electrofusion. Reproduction. 2005;130:553–558. PubMed

Nakajima N, Inomata T, Ito J, Kashiwazaki N. Treatment with proteasome inhibitor MG132 during cloning improves survival and pronuclear number of reconstructed rat embryos. Cloning Stem Cells. 2008;10:461–468. PubMed

Le Bourhis D, Beaujean N, Ruffini S, Vignon X, Gall L. Nuclear remodeling in bovine somatic cell nuclear transfer embryos using MG132-treated recipient oocytes. Cell Reprogramming. 2010;12:729–738. PubMed

You J, Lee E, Bonilla L, Francis J, Koh J, Block J, Chen S, Hansen PJ. Treatment with the proteasome inhibitor MG132 during the end of oocyte maturation improves oocyte competence for development after fertilization in cattle. PLoS ONE. 2012;7:e48613. PubMed PMC

You J, Lee J, Kim J, Park J, Lee E. Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs. Mol Reprod Dev. 2010;77:149–157. PubMed

Shen K, Li X, Dai X, Wang P, Li S, Xiong Z, Chen P, Liu Q, Shi D. Effects of MG132 on the in vitro development and epigenetic modification of Debao porcine somatic cell nuclear transfer embryos. Theriogenology. 2017;94:48–58. PubMed

Higuchi C, Shimizu N, Shin SW, Morita K, Nagai K, Anzai M, Kato H, Mitani T, Yamagata K, Hosoi Y, et al. Ubiquitin-proteasome system modulates zygotic genome activation in early mouse embryos and influences full-term development. J Reprod Dev. 2018;64:65–74. PubMed PMC

Yurttas P, Morency E, Coonrod SA. Use of proteomics to identify highly abundant maternal factors that drive the egg-to-embryo transition. Reproduction. 2010;139:809–823. PubMed

Pennetier S, Perreau C, Uzbekova S, Thélie A, Delaleu B, Mermillod P, Dalbiès-Tran R. MATER protein expression and intracellular localization throughout folliculogenesis and preimplantation embryo development in the bovine. BMC Dev Biol. 2006;6:26. PubMed PMC

Ohsugi M, Zheng P, Baibakov B, Li L, Dean J. Maternally derived FILIA-MATER complex localizes asymmetrically in cleavage-stage mouse embryos. Development. 2008;135:259–269. PubMed

Gao Y, Liu X, Tang B, Li C, Kou Z, Li L, Liu W, Wu Y, Kou X, Li J, et al. Protein expression landscape of mouse embryos during pre-implantation development. Cell Rep. 2017;21:3957–3969. PubMed

Toralova T, Benesova V, Vodickova Kepkova K, Vodicka P, Susor A, Kanka J. Bovine preimplantation embryos with silenced nucleophosmin mRNA are able to develop until the blastocyst stage. Reproduction. 2012;144:349–359. PubMed

Svarcova O, Laurincik J, Avery B, Mlyncek M, Niemann H, Maddox-Hyttel P. Nucleolar development and allocation of key nucleolar proteins require de novo transcription in bovine embryos. Mol Reprod Dev. 2007;74:1428–1435. PubMed

Li L, Lu X, Dean J. The maternal to zygotic transition in mammals. Mol Aspects Med. 2013;34:919–938. PubMed PMC

Peshkin L, Wühr M, Pearl E, Haas W, Freeman RM, Jr, Gerhart JC, Klein AM, Horb M, Gygi SP, Kirschner MW. On the relationship of protein and mRNA dynamics in vertebrate embryonic development. Dev Cell. 2015;35:383–394. PubMed PMC

Lu X, Gao Z, Qin D, Li L. A maternal functional module in the mammalian oocyte-to-embryo transition. Trends Mol Med. 2017;23:1014–1023. PubMed

Bebbere D, Masala L, Albertini DF, Ledda S. The subcortical maternal complex: multiple functions for one biological structure? J Assist Reprod Genet. 2016;33:1431–1438. PubMed PMC

Duesbery NS, Choi T, Brown KD, Wood KW, Resau J, Fukasawa K, Cleveland DW, Vande Woude GF. CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent, cell cycle arrest at metaphase II. Proc Natl Acad Sci USA. 1997;94:9165–9170. PubMed PMC

Allard P, Champigny MJ, Skoggard S, Erkmann JA, Whitfield ML, Marzluff WF, Clarke HJ. Stem-loop binding protein accumulates during oocyte maturation and is not cell-cycle-regulated in the early mouse embryo. J Cell Sci. 2002;115:4577–4586. PubMed PMC

Toralova T, Susor A, Nemcova L, Kepkova K, Kanka J. Silencing CENPF in bovine preimplantation embryo induces arrest at 8-cell stage. Reproduction. 2009;138(5):783–791. PubMed

Collart C, Allen GE, Bradshaw CR, Smith JC, Zegerman P. Titration of four replication factors is essential for the Xenopus laevis midblastula transition. Science. 2013;341:893–896. PubMed PMC

Fisher D. Control of DNA replication by cyclin-dependent kinases in development. Results Probl Cell Differ. 2011;53:201–217. PubMed PMC

Ichikawa K, Noda T, Furuichi Y. Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund–Thomson syndrome caused by the mutation of DNA helicases. Nihon Yakurigaku Zasshi Folia Pharmacol Jpn. 2002;119:219–226. PubMed

Hoki Y, Araki R, Fujimori A, Ohhata T, Koseki H, Fukumura R, Nakamura M, Takahashi H, Noda Y, Kito S, et al. Growth retardation and skin abnormalities of the Recql4-deficient mouse. Hum Mol Genet. 2003;12:2293–2299. PubMed

Wu J, Capp C, Feng L, Hsieh T. Drosophila homologue of the Rothmund–Thomson syndrome gene: essential function in DNA replication during development. Dev Biol. 2008;323:130–142. PubMed PMC

Jeon Y, Ko E, Lee KY, Ko MJ, Park SY, Kang J, Jeon CH, Lee H, Hwang DS. TopBP1 deficiency causes an early embryonic lethality and induces cellular senescence in primary cells. J Biol Chem. 2011;286:5414–5422. PubMed PMC

Sansam CL, Cruz NM, Danielian PS, Amsterdam A, Lau ML, Hopkins N, Lees JA. A vertebrate gene, TICRR, is an essential checkpoint and replication regulator. Genes Dev. 2010;24:183–194. PubMed PMC

Yao L, Chen J, Wu X, Jia S, Meng A. Zebrafish cdc6 hypomorphic mutation causes Meier–Gorlin syndrome-like phenotype. Hum Mol Genet. 2017;26:4168–4180. PubMed PMC

El Dika M, Laskowska-Kaszub K, Koryto M, Dudka D, Prigent C, Tassan JP, Kloc M, Polanski Z, Borsuk E, Kubiak JZ. CDC6 controls dynamics of the first embryonic M-phase entry and progression via CDK1 inhibition. Dev Biol. 2014;396:67–80. PubMed

Zhou ZW, Liu C, Li TL, Bruhn C, Krueger A, Min WK, Wang ZQ, Carr AM. An essential function for the ATR-activation-domain (AAD) of TopBP1 in mouse development and cellular senescence. PLoS Genet. 2013;9:e1003702. PubMed PMC

Eisenmann KM, West RA, Hildebrand D, Kitchen SM, Peng J, Sigler R, Zhang J, Siminovitch KA, Alberts AS. T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice. J Biol Chem. 2007;282:25152–25158. PubMed

Peng J, Wallar BJ, Flanders A, Swiatek PJ, Alberts AS. Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Curr Biol. 2003;13:534–545. PubMed

Cheng Y, Quinn JF, Weiss LA. An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk. Hum Mol Genet. 2013;22:2960–2972. PubMed PMC

Silva T, Bradley RH, Gao Y, Coue M. Xenopus CDC7/DRF1 complex is required for the initiation of DNA replication. J Biol Chem. 2006;281:11569–11576. PubMed

Takahashi TS, Walter JC. Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication. Genes Dev. 2005;19:2295–2300. PubMed PMC

Tikhmyanova N, Coleman TR. Isoform switching of Cdc6 contributes to developmental cell cycle remodeling. Dev Biol. 2003;260:362–375. PubMed

Solc P, Saskova A, Baran V, Kubelka M, Schultz RM, Motlik J. CDC25A phosphatase controls meiosis I progression in mouse oocytes. Dev Biol. 2008;317:260–269. PubMed PMC

Farrell JA, Shermoen AW, Yuan K, O’Farrell PH. Embryonic onset of late replication requires Cdc25 down-regulation. Genes Dev. 2012;26:714–725. PubMed PMC

Sibon OC, Stevenson VA, Theurkauf WE. DNA-replication checkpoint control at the Drosophila midblastula transition. Nature. 1997;388:93–97. PubMed

How great thou ART: biomechanical properties of oocytes and embryos as indicators of quality in assisted reproductive technologies

SCF Ligases and Their Functions in Oogenesis and Embryogenesis-Summary of the Most Important Findings throughout the Animal Kingdom