Induction of autophagy promotes porcine parthenogenetic embryo development under low oxygen conditions
Jilong Zhou
A B * , Tiantian Ji A B * , Hai-Nan He A B , Shu-Yuan Yin A B , Xin Liu A B , Xia Zhang A B and Yi-Liang Miao A B C D
+ Author Affiliations
- Author Affiliations
A Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
B Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China.
C The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
D Corresponding author. Email: miaoyl@mail.hzau.edu.cn
Reproduction, Fertility and Development 32(7) 657-666 https://doi.org/10.1071/RD19322
Submitted: 13 August 2019 Accepted: 13 November 2019 Published: 20 March 2020
Abstract
Autophagy plays an important role in embryo development; however, only limited information is available on how autophagy specifically regulates embryo development, especially under low oxygen culture conditions. In this study we used parthenogenetic activation (PA) of porcine embryos to test the hypothesis that a low oxygen concentration (5%) could promote porcine embryo development by activating autophagy. Immunofluorescence staining revealed that low oxygen tension activated autophagy and alleviated oxidative stress in porcine PA embryos. Development was significantly affected when autophagy was blocked by 3-methyladenine, even under low oxygen culture conditions, with increased reactive oxygen species levels and malondialdehyde content. Furthermore, the decreased expression of pluripotency-associated genes induced by autophagy inhibition could be recovered by treatment with the antioxidant vitamin C. Together, these results demonstrate that low oxygen-induced autophagy regulates embryo development through antioxidant mechanisms in the pig.
Additional keywords: antioxidation, parthenogenetic activation.
References
Absalón-Medina, V. A., Butler, W. R., and Gilbert, R. O. (2014). Preimplantation embryo metabolism and culture systems: experience from domestic animals and clinical implications. J. Assist. Reprod. Genet. 31, 393–409.| Preimplantation embryo metabolism and culture systems: experience from domestic animals and clinical implications.Crossref | GoogleScholarGoogle Scholar | 24682781PubMed |
Bayram, A., Elkhatib, I., Arnanz, A., Linan, A., Ruiz, F., Lawrenz, B., and Fatemi, H. M. (2017). What drives embryo development? Chromosomal normality or mitochondria? Case Rep. Genet. 2017, 4397434.
| What drives embryo development? Chromosomal normality or mitochondria?Crossref | GoogleScholarGoogle Scholar | 28928993PubMed |
Bontekoe, S., Mantikou, E., van Wely, M., Seshadri, S., Repping, S., and Mastenbroek, S. (2012). Low oxygen concentrations for embryo culture in assisted reproductive technologies. Cochrane Database Syst. Rev. 7, CD008950.
| Low oxygen concentrations for embryo culture in assisted reproductive technologies.Crossref | GoogleScholarGoogle Scholar |
Booth, P. J., Holm, P., and Callesen, H. (2005). The effect of oxygen tension on porcine embryonic development is dependent on embryo type. Theriogenology 63, 2040–2052.
| The effect of oxygen tension on porcine embryonic development is dependent on embryo type.Crossref | GoogleScholarGoogle Scholar | 15823359PubMed |
Brahmajosyula, M., and Miyake, M. (2013). Role of peptidylarginine deiminase 4 (PAD4) in pig parthenogenetic preimplantation embryonic development. Zygote 21, 385–393.
| Role of peptidylarginine deiminase 4 (PAD4) in pig parthenogenetic preimplantation embryonic development.Crossref | GoogleScholarGoogle Scholar | 22793990PubMed |
Catt, J. W., and Henman, M. (2000). Toxic effects of oxygen on human embryo development. Hum. Reprod. 15, 199–206.
| Toxic effects of oxygen on human embryo development.Crossref | GoogleScholarGoogle Scholar | 11041525PubMed |
Chen, Y., and Dorn, G. W. (2013). PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340, 471–475.
| PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria.Crossref | GoogleScholarGoogle Scholar | 23620051PubMed |
Dumoulin, J. C., Meijers, C. J., Bras, M., Coonen, E., Geraedts, J. P., and Evers, J. L. (1999). Effect of oxygen concentration on human in-vitro fertilization and embryo culture. Hum. Reprod. 14, 465–469.
| Effect of oxygen concentration on human in-vitro fertilization and embryo culture.Crossref | GoogleScholarGoogle Scholar | 10099995PubMed |
Dunwoodie, S. L. (2009). The role of hypoxia in development of the mammalian embryo. Dev. Cell 17, 755–773.
| The role of hypoxia in development of the mammalian embryo.Crossref | GoogleScholarGoogle Scholar | 20059947PubMed |
Fischer, B., and Bavister, B. D. (1993). Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J. Reprod. Fertil. 99, 673–679.
| Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits.Crossref | GoogleScholarGoogle Scholar | 8107053PubMed |
Gong, G., Hu, L., Liu, Y., Bai, S., Dai, X., Yin, L., Sun, Y., Wang, X., and Hou, L. (2014). Upregulation of HIF-1alpha protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway. Int. J. Mol. Med. 34, 1133–1140.
| Upregulation of HIF-1alpha protein induces mitochondrial autophagy in primary cortical cell cultures through the inhibition of the mTOR pathway.Crossref | GoogleScholarGoogle Scholar | 25017576PubMed |
Grupen, C. G., Verma, P. J., Du, Z. T., McIlfatrick, S. M., Ashman, R. J., and Nottle, M. B. (1999). Activation of in vivo- and in vitro-derived porcine oocytes by using multiple electrical pulses. Reprod. Fertil. Dev. 11, 457–462.
| Activation of in vivo- and in vitro-derived porcine oocytes by using multiple electrical pulses.Crossref | GoogleScholarGoogle Scholar | 11101283PubMed |
Guérin, P., El Mouatassim, S., and Ménézo, Y. (2001). Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum. Reprod. Update 7, 175–189.
| Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings.Crossref | GoogleScholarGoogle Scholar | 11284661PubMed |
Harvey, A. J., Kind, K. L., Pantaleon, M., Armstrong, D. T., and Thompson, J. G. (2004). Oxygen-regulated gene expression in bovine blastocysts. Biol. Reprod. 71, 1108–1119.
| Oxygen-regulated gene expression in bovine blastocysts.Crossref | GoogleScholarGoogle Scholar | 15163614PubMed |
Hu, J., Cheng, D., Gao, X., Bao, J., Ma, X., and Wang, H. (2012). Vitamin C enhances the in vitro development of porcine pre-implantation embryos by reducing oxidative stress. Reprod. Domest. Anim. 47, 873–879.
| Vitamin C enhances the in vitro development of porcine pre-implantation embryos by reducing oxidative stress.Crossref | GoogleScholarGoogle Scholar | 22239270PubMed |
Igarashi, H., Knott, J. G., Schultz, R. M., and Williams, C. J. (2007). Alterations of PLCbeta1 in mouse eggs change calcium oscillatory behavior following fertilization. Dev. Biol. 312, 321–330.
| Alterations of PLCbeta1 in mouse eggs change calcium oscillatory behavior following fertilization.Crossref | GoogleScholarGoogle Scholar | 17961538PubMed |
Iwamoto, M., Onishi, A., Fuchimoto, D., Somfai, T., Takeda, K., Tagami, T., Hanada, H., Noguchi, J., Kaneko, H., Nagai, T., and Kikuchi, K. (2005). Low oxygen tension during in vitro maturation of porcine follicular oocytes improves parthenogenetic activation and subsequent development to the blastocyst stage. Theriogenology 63, 1277–1289.
| Low oxygen tension during in vitro maturation of porcine follicular oocytes improves parthenogenetic activation and subsequent development to the blastocyst stage.Crossref | GoogleScholarGoogle Scholar | 15725436PubMed |
Kang, J. T., Atikuzzaman, M., Kwon, D. K., Park, S. J., Kim, S. J., Moon, J. H., Koo, O. J., Jang, G., and Lee, B. C. (2012). Developmental competence of porcine oocytes after in vitro maturation and in vitro culture under different oxygen concentrations. Zygote 20, 1–8.
| Developmental competence of porcine oocytes after in vitro maturation and in vitro culture under different oxygen concentrations.Crossref | GoogleScholarGoogle Scholar | 21791162PubMed |
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., Kominami, E., Tanaka, K., and Chiba, T. (2005). Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol. 169, 425–434.
| Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice.Crossref | GoogleScholarGoogle Scholar | 15866887PubMed |
Koo, O. J., Park, H. J., Kwon, D. K., Kang, J. T., Jang, G., and Lee, B. C. (2009). Effect of recipient breed on delivery rate of cloned miniature pig. Zygote 17, 203–207.
| Effect of recipient breed on delivery rate of cloned miniature pig.Crossref | GoogleScholarGoogle Scholar | 19393119PubMed |
Latham, K. E., Kutyna, K., and Wang, Q. (1999). Genetic variation in trophectoderm function in parthenogenetic mouse embryos. Dev. Genet. 24, 329–335.
| Genetic variation in trophectoderm function in parthenogenetic mouse embryos.Crossref | GoogleScholarGoogle Scholar | 10322641PubMed |
Leoni, G. G., Rosati, I., Succu, S., Bogliolo, L., Bebbere, D., Berlinguer, F., Ledda, S., and Naitana, S. (2007). A low oxygen atmosphere during IVF accelerates the kinetic of formation of in vitro produced ovine blastocysts. Reprod. Domest. Anim. 42, 299–304.
| A low oxygen atmosphere during IVF accelerates the kinetic of formation of in vitro produced ovine blastocysts.Crossref | GoogleScholarGoogle Scholar | 17506809PubMed |
Liu, S., Bou, G., Sun, R., Guo, S., Xue, B., Wei, R., Cooney, A. J., and Liu, Z. (2015). Sox2 is the faithful marker for pluripotency in pig: evidence from embryonic studies. Dev. Dyn. 244, 619–627.
| Sox2 is the faithful marker for pluripotency in pig: evidence from embryonic studies.Crossref | GoogleScholarGoogle Scholar | 25619399PubMed |
Ma, X., Godar, R. J., Liu, H. Y., and Diwan, A. (2012). Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death. Autophagy 8, 297–309.
| Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death.Crossref | GoogleScholarGoogle Scholar | 22302006PubMed |
Mantikou, E., Bontekoe, S., van Wely, M., Seshadri, S., Repping, S., and Mastenbroek, S. (2013). Low oxygen concentrations for embryo culture in assisted reproductive technologies. Hum. Reprod. Update 19, 209.
| Low oxygen concentrations for embryo culture in assisted reproductive technologies.Crossref | GoogleScholarGoogle Scholar | 23377864PubMed |
Mitalipov, S. M., Nusser, K. D., and Wolf, D. P. (2001). Parthenogenetic activation of rhesus monkey oocytes and reconstructed embryos. Biol. Reprod. 65, 253–259.
| Parthenogenetic activation of rhesus monkey oocytes and reconstructed embryos.Crossref | GoogleScholarGoogle Scholar | 11420247PubMed |
Ng, K. Y. B., Mingels, R., Morgan, H., Macklon, N., and Cheong, Y. (2018). In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review. Hum. Reprod. Update 24, 15–34.
| In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review.Crossref | GoogleScholarGoogle Scholar |
Quinn, P., and Harlow, G. M. (1978). The effect of oxygen on the development of preimplantation mouse embryos in vitro. J. Exp. Zool. 206, 73–80.
| The effect of oxygen on the development of preimplantation mouse embryos in vitro.Crossref | GoogleScholarGoogle Scholar | 702089PubMed |
Rinaudo, P. F., Giritharan, G., Talbi, S., Dobson, A. T., and Schultz, R. M. (2006). Effects of oxygen tension on gene expression in preimplantation mouse embryos. Fertil. Steril. 86, 1252–65, 1265.e1–36.
| Effects of oxygen tension on gene expression in preimplantation mouse embryos.Crossref | GoogleScholarGoogle Scholar | 17008149PubMed |
Schaaf, M. B., Cojocari, D., Keulers, T. G., Jutten, B., Starmans, M. H., de Jong, M. C., Begg, A. C., Savelkouls, K. G., Bussink, J., Vooijs, M., Wouters, B. G., and Rouschop, K. M. (2013). The autophagy associated gene, ULK1, promotes tolerance to chronic and acute hypoxia. Radiother. Oncol. 108, 529–534.
| The autophagy associated gene, ULK1, promotes tolerance to chronic and acute hypoxia.Crossref | GoogleScholarGoogle Scholar | 23849170PubMed |
Seglen, P. O., and Gordon, P. B. (1982). 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl Acad. Sci. USA 79, 1889–1892.
| 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes.Crossref | GoogleScholarGoogle Scholar | 6952238PubMed |
Shintani, T., and Klionsky, D. J. (2004). Autophagy in health and disease: a double-edged sword. Science 306, 990–995.
| Autophagy in health and disease: a double-edged sword.Crossref | GoogleScholarGoogle Scholar | 15528435PubMed |
Stamati, K., Mudera, V., and Cheema, U. (2011). Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering. J. Tissue Eng. 2, 2041731411432365.
| Evolution of oxygen utilization in multicellular organisms and implications for cell signalling in tissue engineering.Crossref | GoogleScholarGoogle Scholar | 22292107PubMed |
Thompson, J. G., Simpson, A. C., Pugh, P. A., Donnelly, P. E., and Tervit, H. R. (1990). Effect of oxygen concentration on in-vitro development of preimplantation sheep and cattle embryos. J. Reprod. Fertil. 89, 573–578.
| Effect of oxygen concentration on in-vitro development of preimplantation sheep and cattle embryos.Crossref | GoogleScholarGoogle Scholar | 2401984PubMed |
Tsukamoto, S., Kuma, A., and Mizushima, N. (2008). The role of autophagy during the oocyte-to-embryo transition. Autophagy 4, 1076–1078.
| The role of autophagy during the oocyte-to-embryo transition.Crossref | GoogleScholarGoogle Scholar | 18849666PubMed |
Waldenström, U., Engström, A. B., Hellberg, D., and Nilsson, S. (2009). Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil. Steril. 91, 2461–2465.
| Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study.Crossref | GoogleScholarGoogle Scholar | 18554591PubMed |
Wong, A., and Cortopassi, G. (2002). Reproducible quantitative PCR of mitochondrial and nuclear DNA copy number using the LightCycler. Methods Mol. Biol. 197, 129–137.
| Reproducible quantitative PCR of mitochondrial and nuclear DNA copy number using the LightCycler.Crossref | GoogleScholarGoogle Scholar | 12013791PubMed |
Yang, Y., Xu, Y., Ding, C., Khoudja, R. Y., Lin, M., Awonuga, A. O., Dai, J., Puscheck, E. E., Rappolee, D. A., and Zhou, C. (2016). Comparison of 2, 5, and 20% O2 on the development of post-thaw human embryos. J. Assist. Reprod. Genet. 33, 919–927.
| Comparison of 2, 5, and 20% O2 on the development of post-thaw human embryos.Crossref | GoogleScholarGoogle Scholar | 27007876PubMed |
Yuan, Y. Q., Van Soom, A., Coopman, F. O., Mintiens, K., Boerjan, M. L., Van Zeveren, A., de Kruif, A., and Peelman, L. J. (2003). Influence of oxygen tension on apoptosis and hatching in bovine embryos cultured in vitro. Theriogenology 59, 1585–1596.
| Influence of oxygen tension on apoptosis and hatching in bovine embryos cultured in vitro.Crossref | GoogleScholarGoogle Scholar | 12559463PubMed |
Yue, Z., Jin, S., Yang, C., Levine, A. J., and Heintz, N. (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl Acad. Sci. USA 100, 15077–15082.
| Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.Crossref | GoogleScholarGoogle Scholar | 14657337PubMed |
Zhao, Y., Chen, G., Zhang, W., Xu, N., Zhu, J. Y., Jia, J., Sun, Z. J., Wang, Y. N., and Zhao, Y. F. (2012). Autophagy regulates hypoxia-induced osteoclastogenesis through the HIF-1alpha/BNIP3 signaling pathway. J. Cell. Physiol. 227, 639–648.
| Autophagy regulates hypoxia-induced osteoclastogenesis through the HIF-1alpha/BNIP3 signaling pathway.Crossref | GoogleScholarGoogle Scholar | 21465467PubMed |
Zhou, J., Yao, W., Li, C., Wu, W., Li, Q., and Liu, H. (2017). Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1alpha in mouse granulosa cells. Cell Death Dis. 8, e3001.
| Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1alpha in mouse granulosa cells.Crossref | GoogleScholarGoogle Scholar | 29144508PubMed |
Zhou, J., Li, C., Yao, W., Alsiddig, M. C., Huo, L., Liu, H., and Miao, Y. L. (2018). Hypoxia-inducible factor-1alpha-dependent autophagy plays a role in glycolysis switch in mouse granulosa cells. Biol. Reprod. 99, 308–318.
| Hypoxia-inducible factor-1alpha-dependent autophagy plays a role in glycolysis switch in mouse granulosa cells.Crossref | GoogleScholarGoogle Scholar | 29546328PubMed |
