Genome transfer for the prevention of female infertility caused by maternal gene mutation

Dandan Bai; Jin Sun; Yanping Jia; Jiqing Yin; Yalin Zhang; Yanhe Li; Rui Gao; Xiling Du; Kunming Li; Jiaming Lin; Zhifen Tu; Yu Wang; Jiaping Pan; Shanshan Liang; Yi Guo; Jingling Ruan; Xiaochen Kou; Yanhong Zhao; Hong Wang; Cizhong Jiang; Fengchao Wang; Xiaoming Teng; Wenqiang Liu; Shaorong Gao

doi:10.1016/j.jgg.2020.06.002

Volume 47 Issue 6

Jun. 2020

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2020 > 47(6): 311-319

PDF( 2823 KB)

Genome transfer for the prevention of female infertility caused by maternal gene mutation

doi: 10.1016/j.jgg.2020.06.002

a
Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
b
National Institute of Biological Sciences, NIBS, Beijing, 102206, China

More Information

Corresponding author: E-mail address: tengxiaoming@51mch.com (Xiaoming Teng); E-mail address: liuwenqiang@tongji.edu.cn (Wenqiang Liu); E-mail address: gaoshaorong@tongji.edu.cn (Shaorong Gao)
Publish Date: 2020-06-25

Abstract

Abstract

Poor oocyte quality is associated with early embryo developmental arrest and infertility. Maternal gene plays crucial roles in the regulation of oocyte maturation, and its mutation is a common cause of female infertility. However, how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive. Here, we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutation–caused female infertility. We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation (ZGA) during the maternal-zygotic transition. We next perform genome transfer at the oocyte (spindle transfer or polar body transfer) and zygote (early pronuclear transfer or late pronuclear transfer) stages to validate the feasibility of preventing Zar1 mutation–caused infertility. We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring. Moreover, those pups grow to adulthood and show normal fertility. Therefore, our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation.
- Infertility,
- Oocytes,
- Maternal-zygotic transition,
- ZGA,
- Spindle transfer,
- Genome transfer

These authors contributed equally to this work.

FullText(HTML)

References(38)

References

[1]	Alazami, A.M., Awad, S.M., Coskun, S., Al-Hassan, S., Hijazi, H., Abdulwahab, F.M., Poizat, C., Alkuraya, F.S., 2015. TLE6 mutation causes the earliest known human embryonic lethality. Genome Biol 16.
[2]	Bultman, S.J., Gebuhr, T.C., Pan, H., Svoboda, P., Schultz, R.M., Magnuson, T., 2006. Maternal BRG1 regulates zygotic genome activation in the mouse. Genes Dev 20, 1744-1754.
[3]	Burns, K.H., Viveiros, M.M., Ren, Y.S., Wang, P., DeMayo, F.J., Frail, D.E., Eppig, J.J., Matzuk, M.M., 2003. Roles of NPM2 in chromatin and nucleolar organization in oocytes and embryos. Science 300, 633-636.
[4]	Cecconi, S., Ciccarelli, C., Barberi, M., Macchiarelli, G., Canipari, R., 2004. Granulosa cell-oocyte interactions. Eur J Obstet Gyn R B 115, S19-S22.
[5]	Chen, B., Wang, W., Peng, X., Jiang, H., Zhang, S., Li, D., Li, B., Fu, J., Kuang, Y., Sun, X., Wang, X., Zhang, Z., Wu, L., Zhou, Z., Lyu, Q., Yan, Z., Mao, X., Xu, Y., Mu, J., Li, Q., Jin, L., He, L., Sang, Q., Wang, L., 2019. The comprehensive mutational and phenotypic spectrum of TUBB8 in female infertility. Eur J Hum Genet 27, 300-307.
[6]	Christians, E., Davis, A.A., Thomas, S.D., Benjamin, I.J., 2000. Maternal effect of Hsf1 on reproductive success. Nature 407, 693-694.
[7]	Craven, L., Alston, C.L., Taylor, R.W., Turnbull, D.M., 2017. Recent Advances in Mitochondrial Disease. Annu Rev Genom Hum G 18, 257-275.
[8]	Craven, L., Tuppen, H.A., Greggains, G.D., Harbottle, S.J., Murphy, J.L., Cree, L.M., Murdoch, A.P., Chinnery, P.F., Taylor, R.W., Lightowlers, R.N., Herbert, M., Turnbull, D.M., 2010. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 465, 82-85.
[9]	Feng, R.Z., Sang, Q., Kuang, Y.P., Sun, X.X., Yan, Z., Zhang, S.Z., Shi, J.Z., Tian, G.L., Luchniak, A., Fukuda, Y., Li, B., Yu, M., Chen, J.L., Xu, Y., Guo, L., Qu, R.G., Wang, X.Q., Sun, Z.G., Liu, M., Shi, H.J., Wang, H.Y., Feng, Y., Shao, R.J., Chai, R.J., Li, Q.L., Xing, Q.H., Zhang, R., Nogales, E., Jin, L., He, L., Gupta, M.L., Cowan, N.J., Wang, L., 2016. Mutations in TUBB8 and Human Oocyte Meiotic Arrest. New Engl J Med 374, 223-232.
[10]	Huang, C.C., Cheng, T.C., Chang, H.H., Chang, C.C., Chen, C.I., Liu, J.E., Lee, M.S., 1999. Birth after the injection of sperm and the cytoplasm of tripronucleate zygotes into metaphase II oocytes in patients with repeated implantation failure after assisted fertilization procedures. Fertil Steril 72, 702-706.
[11]	Hyslop, L.A., Blakeley, P., Craven, L., Richardson, J., Fogarty, N.M.E., Fragouli, E., Lamb, M., Wamaitha, S.E., Prathalingam, N., Zhang, Q., O'Keefe, H., Takeda, Y., Arizzi, L., Alfarawati, S., Tuppen, H.A., Irving, L., Kalleas, D., Choudhary, M., Wells, D., Murdoch, A.P., Turnbull, D.M., Niakan, K.K., Herbert, M., 2016. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature 534, 383-386.
[12]	Liu, Y.S., Lu, X.K., Shi, J.C., Yu, X.J., Zhang, X.X., Zhu, K., Yi, Z.H., Duan, E.K., Li, L., 2016. BTG4 is a key regulator for maternal mRNA clearance during mouse early embryogenesis. J Mol Cell Biol 8, 366-368.
[13]	Lu, X.K., Gao, Z., Qin, D.D., Li, L., 2017. A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition. Trends Mol Med 23, 1014-1023.
[14]	Luke, B., 2017. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies. Am J Obstet Gynecol 217, 270-281.
[15]	Ma, H., O'Neil, R.C., Marti Gutierrez, N., Hariharan, M., Zhang, Z.Z., He, Y., Cinnioglu, C., Kayali, R., Kang, E., Lee, Y., Hayama, T., Koski, A., Nery, J., Castanon, R., Tippner-Hedges, R., Ahmed, R., Van Dyken, C., Li, Y., Olson, S., Battaglia, D., Lee, D.M., Wu, D.H., Amato, P., Wolf, D.P., Ecker, J.R., Mitalipov, S., 2017. Functional Human Oocytes Generated by Transfer of Polar Body Genomes. Cell Stem Cell 20, 112-119.
[16]	Masala, L., Ariu, F., Bogliolo, L., Bellu, E., Ledda, S., Bebbere, D., 2018. Delay in maternal transcript degradation in ovine embryos derived from low competence oocytes. Mol Reprod Dev 85, 427-439.
[17]	Miao, L., Yuan, Y., Cheng, F., Fang, J., Zhou, F., Ma, W., Jiang, Y., Huang, X., Wang, Y., Shan, L., Chen, D., Zhang, J., 2017. Translation repression by maternal RNA binding protein Zar1 is essential for early oogenesis in zebrafish. Development 144, 128-138.
[18]	Minami, N., Suzuki, T., Tsukamoto, S., 2007. Zygotic gene activation and maternal factors in mammals. J Reprod Dev 53, 707-715.
[19]	Pasternak, M., Pfender, S., Santhanam, B., Schuh, M., 2016. The BTG4 and CAF1 complex prevents the spontaneous activation of eggs by deadenylating maternal mRNAs. Open Biol 6.
[20]	Payer, B., Saitou, M., Barton, S.C., Thresher, R., Dixon, J.P., Zahn, D., Colledge, W.H., Carlton, M.B., Nakano, T., Surani, M.A., 2003. Stella is a maternal effect gene required for normal early development in mice. Curr Biol 13, 2110-2117.
[21]	Peng, H., Chang, B., Lu, C., Su, J., Wu, Y., Lv, P., Wang, Y., Liu, J., Zhang, B., Quan, F., Guo, Z., Zhang, Y., 2012. Nlrp2, a maternal effect gene required for early embryonic development in the mouse. PLoS One 7, e30344.
[22]	Qian, J.H., Nguyen, N.M.P., Rezaei, M., Huang, B., Tao, Y.L., Zhang, X.F., Cheng, Q., Yang, H.J., Asangla, A., Majewski, J., Slim, R., 2018. Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles. Eur J Hum Genet 26, 1007-1013.
[23]	Roest, H.P., Baarends, W.M., de Wit, J., van Klaveren, J.W., Wassenaar, E., Hoogerbrugge, J.W., van Cappellen, W.A., Hoeijmakers, J.H., Grootegoed, J.A., 2004. The ubiquitin-conjugating DNA repair enzyme HR6A is a maternal factor essential for early embryonic development in mice. Mol Cell Biol 24, 5485-5495.
[24]	Rong, Y., Ji, S.Y., Zhu, Y.Z., Wu, Y.W., Shen, L., Fan, H.Y., 2019. ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation. Nucleic Acids Res 47, 11387-11402.
[25]	Sang, Q., Li, B., Kuang, Y.P., Wang, X.Q., Zhang, Z.H., Chen, B.B., Wu, L., Lyu, Q.F., Fu, Y.L., Yan, Z., Mao, X.Y., Xu, Y., Mu, J., Li, Q.L., Jin, L., He, L., Wang, L., 2018. Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility. Am J Hum Genet 102, 649-657.
[26]	Sha, Q.Q., Dai, X.X., Dang, Y.J., Tang, F.C., Liu, J.P., Zhang, Y.L., Fan, H.Y., 2017. A MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocytes. Development 144, 452-463.
[27]	Su, Y.Q., Sugiura, K., Woo, Y., Wigglesworth, K., Kamdar, S., Affourtit, J., Eppig, J.J., 2007. Selective degradation of transcripts during meiotic maturation of mouse oocytes. Dev Biol 302, 104-117.
[28]	Tang, F.C., Barbacioru, C., Nordman, E., Li, B., Xu, N.L., Bashkirov, V.I., Lao, K.Q., Surani, M.A., 2010. RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protoc 5, 516-535.
[29]	Tong, Z.B., Gold, L., Pfeifer, K.E., Dorward, H., Lee, E., Bondy, C.A., Dean, J., Nelson, L.M., 2000. Mater, a maternal effect gene required for early embryonic development in mice. Nat Genet 26, 267-268.
[30]	Wang, T., Sha, H., Ji, D., Zhang, H.L., Chen, D., Cao, Y., Zhu, J., 2014a. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases. Cell 157, 1591-1604.
[31]	Wang, T., Sha, H.Y., Ji, D.M., Zhang, H.L., Chen, D.W., Cao, Y.X., Zhu, J.H., 2014b. Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases. Cell 157, 1591-1604.
[32]	Wang, X., Song, D., Mykytenko, D., Kuang, Y., Lv, Q., Li, B., Chen, B., Mao, X., Xu, Y., Zukin, V., Mazur, P., Mu, J., Yan, Z., Zhou, Z., Li, Q., Liu, S., Jin, L., He, L., Sang, Q., Sun, Z., Dong, X., Wang, L., 2018. Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest. Reprod Biomed Online 36, 698-704.
[33]	Wu, X., Viveiros, M.M., Eppig, J.J., Bai, Y., Fitzpatrick, S.L., Matzuk, M.M., 2003. Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition. Nat Genet 33, 187-191.
[34]	Yamamoto, T.M., Cook, J.M., Kotter, C.V., Khat, T., Silva, K.D., Ferreyros, M., Holt, J.W., Knight, J.D., Charlesworth, A., 2013. Zar1 represses translation in Xenopus oocytes and binds to the TCS in maternal mRNAs with different characteristics than Zar2. Biochim Biophys Acta 1829, 1034-1046.
[35]	Yu, C., Ji, S.Y., Sha, Q.Q., Dang, Y., Zhou, J.J., Zhang, Y.L., Liu, Y., Wang, Z.W., Hu, B., Sun, Q.Y., Sun, S.C., Tang, F., Fan, H.Y., 2016. BTG4 is a meiotic cell cycle-coupled maternal-zygotic-transition licensing factor in oocytes. Nat Struct Mol Biol 23, 387-394.
[36]	Zhang, J., Liu, H., Luo, S.Y., Lu, Z., Chavez-Badiola, A., Liu, Z.T., Yang, M.X., Merhi, Z., Silber, S.J., Munne, S., Konstantinidis, M., Wells, D., Tang, J.J., Huang, T.S., 2017a. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online 34, 361-368.
[37]	Zhang, J., Zhuang, G.L., Zeng, Y., Grifo, J.M., Acosta, C., Shu, Y.M., Liu, H., 2017b. Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF. Reprod Biomed Online 33, 529-533.
[38]	Zhang, K., Smith, G.W., 2015. Maternal control of early embryogenesis in mammals. Reprod Fertil Dev 27, 880-896.