Skip to main content
Erschienen in: Reproductive Medicine and Biology 2/2015

01.04.2015 | Review Article

Autophagic activity as an indicator for selecting good quality embryos

verfasst von: Satoshi Tsukamoto

Erschienen in: Reproductive Medicine and Biology | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Is it possible to predict the quality of embryos that appear to be morphologically identical when viewed under a microscope? Thirty-five years have passed since the world’s first human birth from in vitro fertilization. While the dissemination of assisted reproduction technologies during this time has been remarkable, the evaluation of embryo quality in both humans and mice currently relies entirely on morphological observation. More efficient infertility treatments will likely be possible if high-quality embryos can be selected by screening. To develop a novel quality evaluation method that does not rely on morphology, we focused on autophagy, one of the molecular mechanisms essential for the early embryonic development. Autophagy is a massive cytoplasmic degradation pathway mediated by the lysosome. Our previous studies have demonstrated that fertilization-induced autophagy is essential for preimplantation embryonic development. This autophagy is thought to supply the nutrients and amino acids necessary for maintaining subsequent embryo development, through the bulk degradation of maternal cytoplasmic factors that are accumulated during oogenesis. Here, we briefly summarize autophagy and its physiological function, and describe a recently developed method for using autophagic activity as an indicator to predict embryo quality.
Literatur
1.
Zurück zum Zitat Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978;2:366.CrossRefPubMed Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978;2:366.CrossRefPubMed
4.
Zurück zum Zitat Kjellberg AT, Carlsson P, Bergh C. Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis. Hum Reprod. 2006;21:210–6.CrossRefPubMed Kjellberg AT, Carlsson P, Bergh C. Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis. Hum Reprod. 2006;21:210–6.CrossRefPubMed
5.
Zurück zum Zitat Baczkowski T, Kurzawa R, Glabowski W. Methods of embryo scoring in in vitro fertilization. Reprod Biol. 2004;4:5–22.PubMed Baczkowski T, Kurzawa R, Glabowski W. Methods of embryo scoring in in vitro fertilization. Reprod Biol. 2004;4:5–22.PubMed
6.
Zurück zum Zitat Minami N, Suzuki T, Tsukamoto S. Zygotic gene activation and maternal factors in mammals. J Reprod Dev. 2007;53:707–15.CrossRefPubMed Minami N, Suzuki T, Tsukamoto S. Zygotic gene activation and maternal factors in mammals. J Reprod Dev. 2007;53:707–15.CrossRefPubMed
7.
8.
Zurück zum Zitat Schier AF. The maternal-zygotic transition: death and birth of RNAs. Science. 2007;316:406–7.CrossRefPubMed Schier AF. The maternal-zygotic transition: death and birth of RNAs. Science. 2007;316:406–7.CrossRefPubMed
9.
Zurück zum Zitat Yi YJ, Nagyova E, Manandhar G, Prochazka R, Sutovsky M, Park CS, et al. Proteolytic activity of the 26S proteasome is required for the meiotic resumption, germinal vesicle breakdown, and cumulus expansion of porcine cumulus-oocyte complexes matured in vitro. Biol Reprod. 2008;78:115–26.CrossRefPubMed Yi YJ, Nagyova E, Manandhar G, Prochazka R, Sutovsky M, Park CS, et al. Proteolytic activity of the 26S proteasome is required for the meiotic resumption, germinal vesicle breakdown, and cumulus expansion of porcine cumulus-oocyte complexes matured in vitro. Biol Reprod. 2008;78:115–26.CrossRefPubMed
10.
Zurück zum Zitat 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;100:550–5.CrossRefPubMedCentralPubMed 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;100:550–5.CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Shin SW, Tokoro M, Nishikawa S, Lee HH, Hatanaka Y, Nishihara T, et al. Inhibition of the ubiquitin-proteasome system leads to delay of the onset of ZGA gene expression. J Reprod Dev. 2010;56:655–63.CrossRefPubMed Shin SW, Tokoro M, Nishikawa S, Lee HH, Hatanaka Y, Nishihara T, et al. Inhibition of the ubiquitin-proteasome system leads to delay of the onset of ZGA gene expression. J Reprod Dev. 2010;56:655–63.CrossRefPubMed
12.
13.
Zurück zum Zitat Oku M, Sakai Y. Peroxisomes as dynamic organelles: autophagic degradation. FEBS J. 2010;277:3289–94.CrossRefPubMed Oku M, Sakai Y. Peroxisomes as dynamic organelles: autophagic degradation. FEBS J. 2010;277:3289–94.CrossRefPubMed
15.
Zurück zum Zitat Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321:117–20.CrossRefPubMed Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321:117–20.CrossRefPubMed
17.
Zurück zum Zitat Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107–32.CrossRefPubMed Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107–32.CrossRefPubMed
18.
Zurück zum Zitat Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006;441:880–4.CrossRefPubMed Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006;441:880–4.CrossRefPubMed
19.
Zurück zum Zitat Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441:885–9.CrossRefPubMed Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441:885–9.CrossRefPubMed
21.
Zurück zum Zitat Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–5.PubMedCentralPubMed Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–5.PubMedCentralPubMed
24.
Zurück zum Zitat De Duve C, Gianetto R, Appelmans F, Wattiaux R. Enzymic content of the mitochondria fraction. Nature. 1953;172:1143–4.CrossRef De Duve C, Gianetto R, Appelmans F, Wattiaux R. Enzymic content of the mitochondria fraction. Nature. 1953;172:1143–4.CrossRef
25.
Zurück zum Zitat Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333:169–74.CrossRefPubMed Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333:169–74.CrossRefPubMed
26.
27.
Zurück zum Zitat Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–8.CrossRefPubMedCentralPubMed Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–8.CrossRefPubMedCentralPubMed
28.
Zurück zum Zitat Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004;15:1101–11.CrossRefPubMedCentralPubMed Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004;15:1101–11.CrossRefPubMedCentralPubMed
32.
Zurück zum Zitat Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009;20:1981–91.CrossRefPubMedCentralPubMed Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009;20:1981–91.CrossRefPubMedCentralPubMed
33.
Zurück zum Zitat Yamamoto A, Mizushima N, Tsukamoto S. Fertilization-induced autophagy in mouse embryos is independent of mTORC1. Biol Reprod. 2014;91:7.CrossRefPubMed Yamamoto A, Mizushima N, Tsukamoto S. Fertilization-induced autophagy in mouse embryos is independent of mTORC1. Biol Reprod. 2014;91:7.CrossRefPubMed
34.
35.
Zurück zum Zitat Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, et al. A gene network regulating lysosomal biogenesis and function. Science. 2009;325:473–7.PubMed Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, et al. A gene network regulating lysosomal biogenesis and function. Science. 2009;325:473–7.PubMed
36.
Zurück zum Zitat Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Huynh T, et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012;31:1095–108.CrossRefPubMedCentralPubMed Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Huynh T, et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012;31:1095–108.CrossRefPubMedCentralPubMed
37.
Zurück zum Zitat Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012;5:ra42.PubMedCentralPubMed Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012;5:ra42.PubMedCentralPubMed
38.
Zurück zum Zitat Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Huynh T, et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012;31:1095–108.CrossRefPubMedCentralPubMed Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Huynh T, et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012;31:1095–108.CrossRefPubMedCentralPubMed
39.
Zurück zum Zitat van der Vos KE, Eliasson P, Proikas-Cezanne T, Vervoort SJ, van Boxtel R, Putker M, et al. Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy. Nat Cell Biol. 2012;14:829–37.CrossRefPubMed van der Vos KE, Eliasson P, Proikas-Cezanne T, Vervoort SJ, van Boxtel R, Putker M, et al. Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy. Nat Cell Biol. 2012;14:829–37.CrossRefPubMed
40.
Zurück zum Zitat Tsukamoto S, Hara T, Yamamoto A, Kito S, Minami N, Kubota T, et al. Fluorescence-based visualization of autophagic activity predicts mouse embryo viability. Sci Rep. 2014;4:4533.PubMedCentralPubMed Tsukamoto S, Hara T, Yamamoto A, Kito S, Minami N, Kubota T, et al. Fluorescence-based visualization of autophagic activity predicts mouse embryo viability. Sci Rep. 2014;4:4533.PubMedCentralPubMed
41.
Zurück zum Zitat Shvets E, Fass E, Elazar Z. Utilizing flow cytometry to monitor autophagy in living mammalian cells. Autophagy. 2008;4:621–8.CrossRefPubMed Shvets E, Fass E, Elazar Z. Utilizing flow cytometry to monitor autophagy in living mammalian cells. Autophagy. 2008;4:621–8.CrossRefPubMed
42.
Zurück zum Zitat Tsukamoto S, Hara T, Yamamoto A, Ohta Y, Wada A, Ishida Y, et al. Functional analysis of lysosomes during mouse preimplantation embryo development. J Reprod Dev. 2013;59:33–9.PubMedCentralPubMed Tsukamoto S, Hara T, Yamamoto A, Ohta Y, Wada A, Ishida Y, et al. Functional analysis of lysosomes during mouse preimplantation embryo development. J Reprod Dev. 2013;59:33–9.PubMedCentralPubMed
43.
47.
Zurück zum Zitat Fukuda M. Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem. 1991;266:21327–30.PubMed Fukuda M. Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. J Biol Chem. 1991;266:21327–30.PubMed
48.
Zurück zum Zitat Chester N, Kuo F, Kozak C, O’Hara CD, Leder P. Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene. Genes Dev. 1998;12:3382–93.CrossRefPubMedCentralPubMed Chester N, Kuo F, Kozak C, O’Hara CD, Leder P. Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene. Genes Dev. 1998;12:3382–93.CrossRefPubMedCentralPubMed
49.
Zurück zum Zitat Mizutani E, Yamagata K, Ono T, Akagi S, Geshi M, Wakayama T. Abnormal chromosome segregation at early cleavage is a major cause of the full-term developmental failure of mouse clones. Dev Biol. 2012;364:56–65.CrossRefPubMed Mizutani E, Yamagata K, Ono T, Akagi S, Geshi M, Wakayama T. Abnormal chromosome segregation at early cleavage is a major cause of the full-term developmental failure of mouse clones. Dev Biol. 2012;364:56–65.CrossRefPubMed
50.
Zurück zum Zitat Yamagata K, Suetsugu R, Wakayama T. Assessment of chromosomal integrity using a novel live-cell imaging technique in mouse embryos produced by intracytoplasmic sperm injection. Hum Reprod. 2009;24:2490–9.CrossRefPubMed Yamagata K, Suetsugu R, Wakayama T. Assessment of chromosomal integrity using a novel live-cell imaging technique in mouse embryos produced by intracytoplasmic sperm injection. Hum Reprod. 2009;24:2490–9.CrossRefPubMed
51.
Zurück zum Zitat Rello-Varona S, Lissa D, Shen S, Niso-Santano M, Senovilla L, Marino G, et al. Autophagic removal of micronuclei. Cell Cycle. 2012;11:170–6.CrossRefPubMed Rello-Varona S, Lissa D, Shen S, Niso-Santano M, Senovilla L, Marino G, et al. Autophagic removal of micronuclei. Cell Cycle. 2012;11:170–6.CrossRefPubMed
52.
Zurück zum Zitat Jasensky J, Swain JE. Peering beneath the surface: novel imaging techniques to noninvasively select gametes and embryos for ART. Biol Reprod. 2013;89:105.CrossRefPubMed Jasensky J, Swain JE. Peering beneath the surface: novel imaging techniques to noninvasively select gametes and embryos for ART. Biol Reprod. 2013;89:105.CrossRefPubMed
53.
Zurück zum Zitat Ajduk A, Ilozue T, Windsor S, Yu Y, Seres KB, Bomphrey RJ, et al. Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability. Nat Commun. 2011;2:417.CrossRefPubMedCentralPubMed Ajduk A, Ilozue T, Windsor S, Yu Y, Seres KB, Bomphrey RJ, et al. Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability. Nat Commun. 2011;2:417.CrossRefPubMedCentralPubMed
Metadaten
Titel
Autophagic activity as an indicator for selecting good quality embryos
verfasst von
Satoshi Tsukamoto
Publikationsdatum
01.04.2015
Verlag
Springer Japan
Erschienen in
Reproductive Medicine and Biology / Ausgabe 2/2015
Print ISSN: 1445-5781
Elektronische ISSN: 1447-0578
DOI
https://doi.org/10.1007/s12522-014-0197-x

Weitere Artikel der Ausgabe 2/2015

Reproductive Medicine and Biology 2/2015 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.