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Paternal hypoxia exposure impairs fertilization process and preimplantation embryo development

Published online by Cambridge University Press:  23 June 2021

Hai-Ping Tao ,
Gong-Xue Jia ,
Xiao-Na Zhang ,
Yu-Jun Wang ,
Bin-Ye Li  and
Qi-En Yang Open the ORCID record for Qi-En Yang [Opens in a new window]
Hai-Ping Tao
Affiliation:
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China University of Chinese Academy of Sciences, Beijing100049, China Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, Qinghai, China
Gong-Xue Jia
Affiliation:
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China University of Chinese Academy of Sciences, Beijing100049, China Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, Qinghai, China
Xiao-Na Zhang
Affiliation:
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China University of Chinese Academy of Sciences, Beijing100049, China
Yu-Jun Wang
Affiliation:
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China University of Chinese Academy of Sciences, Beijing100049, China
Bin-Ye Li
Affiliation:
Center for Reproductive Medicine, Qinghai People’s Hospital, Xining810007, Qinghai, China.
Qi-En Yang*
Affiliation:
Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China University of Chinese Academy of Sciences, Beijing100049, China Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, Qinghai, China
*
Author for correspondence: Qi-En Yang. Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining810001, China. Email: yangqien@nwipb.cas.cn
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Summary

Environmental hypoxia exposure causes fertility problems in human and animals. Compelling evidence suggests that chronic hypoxia impairs spermatogenesis and reduces sperm motility. However, it is unclear whether paternal hypoxic exposure affects fertilization and early embryo development. In the present study, we exposed male mice to high altitude (3200 m above sea level) for 7 or 60 days to evaluate the effects of hypoxia on sperm quality, zygotic DNA methylation and blastocyst formation. Compared with age-matched controls, hypoxia-treated males exhibited reduced fertility after mating with normoxic females as a result of defects in sperm motility and function. Results of in vitro fertilization (IVF) experiments revealed that 60 days’ exposure significantly reduced cleavage and blastocyst rates by 30% and 70%, respectively. Immunohistochemical staining of pronuclear formation indicated that the pronuclear formation process was disturbed and expression of imprinted genes was reduced in early embryos after paternal hypoxia. Overall, the findings of this study suggested that exposing male mice to hypoxia impaired sperm function and affected key events during early embryo development in mammals.

Keywords

BlastocystFertilizationHypoxiaSperm qualityZygote

Information

Type
Research Article
Information
Zygote , Volume 30 , Issue 1 , February 2022 , pp. 48 - 56
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

References

Aitken, RJ, Buckingham, DW and Fang, HG (1993). Analysis of the responses of human spermatozoa to A23187 employing a novel technique for assessing the acrosome reaction. J Androl 14, 132–41.Google ScholarPubMed
Baccetti, B and Afzelius, BA (1976). The biology of the sperm cell. Monogr Dev Biol 10, 1–254.Google Scholar
Bai, G, Yang, B, Tong, W and Li, H (2018). Hypobaric hypoxia causes impairment of spermatogenesis in developing rats at pre-puberty. Andrologia. doi: 10.1111/and.13000. Epub ahead of print.CrossRefGoogle Scholar
Campos, EI, Stafford, JM and Reinberg, D (2014). Epigenetic inheritance: histone bookmarks across generations. Trends Cell Biol 24, 664–74.CrossRefGoogle Scholar
Chao, SB, Guo, L, Ou, XH, Luo, SM, Wang, ZB, Schatten, H, Gao, GL and Sun, QY (2012). Heated spermatozoa: effects on embryonic development and epigenetics. Hum Reprod 27, 1016–24.CrossRefGoogle ScholarPubMed
Chen, M, Shen, H, Zhu, L, Yang, H, Ye, P, Liu, P, Gu, Y and Chen, S (2019). Berberine attenuates hypoxia-induced pulmonary arterial hypertension via bone morphogenetic protein and transforming growth factor-β signaling. J Cell Physiol 234, 17482–93.CrossRefGoogle ScholarPubMed
Cohen, JE and Small, C (1998). Hypsographic demography: the distribution of human population by altitude. Proc Natl Acad Sci USA 95, 14009–14.CrossRefGoogle ScholarPubMed
Colaco, S and Sakkas, D (2018). Paternal factors contributing to embryo quality. J Assist Reprod Genet 35, 1953–68.CrossRefGoogle ScholarPubMed
de Rooij, DG and Russell, LD (2000). All you wanted to know about spermatogonia but were afraid to ask. J Androl 21, 776–98.Google Scholar
Dunaeva, TY, Trofimova, LK, Graf, AV, Maslova, MV, Maklakova, AS, Krushinskaya, YV and Sokolova, NA (2008). Transgeneration effects of antenatal acute hypoxia during early organogenesis. Bull Exp Biol Med 146, 385–7.CrossRefGoogle ScholarPubMed
Farias, JG, Zepeda, A, Castillo, R, Figueroa, E, Ademoyero, OT and Pulgar, VM (2018). Chronic hypobaric hypoxia diminishes the expression of base excision repair OGG1 enzymes in spermatozoa. Andrologia 50, doi: 10.1111/and.12876. Epub.CrossRefGoogle Scholar
Fuentes-Mascorro, G, Serrano, H and Rosado, A (2000). Sperm chromatin. Arch Androl 45, 215–25.CrossRefGoogle ScholarPubMed
Gonzales, GF, Lozano-Hernandez, R, Gasco, M, Gonzales-Castaneda, C and Tapia, V (2012). Resistance of sperm motility to serum testosterone in men with excessive erythrocytosis at high altitude. Horm Metab Res 44, 987–92.Google ScholarPubMed
Gruber, M, Mathew, LK, Runge, AC, Garcia, JA and Simon, MC (2010). EPAS1 is required for spermatogenesis in the postnatal mouse testis. Biol Reprod 82, 1227–36.CrossRefGoogle ScholarPubMed
Gu, NH, Zhao, WL, Wang, GS and Sun, F (2019). Comparative analysis of mammalian sperm ultrastructure reveals relationships between sperm morphology, mitochondrial functions and motility. Reprod Biol Endocrinol 17, 66.CrossRefGoogle ScholarPubMed
Guo, F, Li, X, Liang, D, Li, T, Zhu, P, Guo, H, Wu, X, Wen, L, Gu, TP, Hu, B, Walsh, CP, Li, J, Tang, F and Xu, GL (2014). Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell 15, 447–59.CrossRefGoogle ScholarPubMed
Hao, SL, Ni, FD and Yang, WX (2019). The dynamics and regulation of chromatin remodeling during spermiogenesis. Gene 706, 201–10.CrossRefGoogle ScholarPubMed
He, J, Cui, J, Wang, R, Gao, L, Gao, X, Yang, L, Zhang, Q, Cao, J and Yu, W (2015). Exposure to hypoxia at high altitude (5380 m) for 1 year induces reversible effects on semen quality and serum reproductive hormone levels in young male adults. High Alt Med Biol 16, 216–22.CrossRefGoogle ScholarPubMed
Illum, LRH, Bak, ST, Lund, S and Nielsen, AL (2018). DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line. J Mol Endocrinol 60, R39–56.CrossRefGoogle ScholarPubMed
Iqbal, K, Jin, SG, Pfeifer, GP and Szabo, PE (2011). Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci USA 108, 3642–7.CrossRefGoogle ScholarPubMed
Jankovic Velickovic, L and Stefanovic, V (2014). Hypoxia and spermatogenesis. Int Urol Nephrol 46, 887–94.CrossRefGoogle ScholarPubMed
Jia, G, Fu, X, Cheng, K, Yue, M, Jia, B, Hou, Y and Zhu, S (2015). Spermatozoa cryopreservation alters pronuclear formation and zygotic DNA demethylation in mice. Theriogenology 83, 1000–6.CrossRefGoogle ScholarPubMed
Klastrup, LK, Bak, ST and Nielsen, AL (2019). The influence of paternal diet on sncRNA-mediated epigenetic inheritance. Mol Genet Genom 294, 1–11.CrossRefGoogle ScholarPubMed
Krause, W (1995). Computer-assisted semen analysis systems: comparison with routine evaluation and prognostic value in male fertility and assisted reproduction. Hum Reprod 10(Suppl 1), 60–6.CrossRefGoogle ScholarPubMed
Le Blevec, E, Muronova, J, Ray, PF and Arnoult, C (2020). Paternal epigenetics: mammalian sperm provide much more than DNA at fertilization. Mol Cell Endocrinol 518, 110964.CrossRefGoogle ScholarPubMed
Legoff, L, D’Cruz, SC, Tevosian, S, Primig, M and Smagulova, F (2019). Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development. Cells 8, 1559.CrossRefGoogle ScholarPubMed
Liao, W, Cai, M, Chen, J, Huang, J, Liu, F, Jiang, C and Gao, Y (2010). Hypobaric hypoxia causes deleterious effects on spermatogenesis in rats. Reproduction 139, 1031–8.CrossRefGoogle ScholarPubMed
Lim, CY, Knowles, BB, Solter, D and Messerschmidt, DM (2016). Epigenetic control of early mouse development. Curr Top Dev Biol 120, 311–60.CrossRefGoogle ScholarPubMed
Luo, Y, Liao, W, Chen, Y, Cui, J, Liu, F, Jiang, C, Gao, W and Gao, Y (2011). Altitude can alter the mtDNA copy number and nDNA integrity in sperm. J Assist Reprod Genet 28, 951–6.CrossRefGoogle ScholarPubMed
Lyko, F (2018). The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev. Genet 19, 81–92.CrossRefGoogle ScholarPubMed
Meyer, RG, Ketchum, CC and Meyer-Ficca, ML (2017). Heritable sperm chromatin epigenetics: a break to remember. Biol Reprod 97, 784–97.CrossRefGoogle Scholar
Reyes, JG, Farias, JG, Henriquez-Olavarrieta, S, Madrid, E, Parraga, M, Zepeda, AB and Moreno, RD (2012). The hypoxic testicle: physiology and pathophysiology. Oxid Med Cell Longev 2012, 929285.CrossRefGoogle Scholar
Saxena, DK (1995). Effect of hypoxia by intermittent altitude exposure on semen characteristics and testicular morphology of male rhesus monkeys. Int J Biometeorol 38, 137–40.CrossRefGoogle ScholarPubMed
Tateno, H, Krapf, D, Hino, T, Sanchez-Cardenas, C, Darszon, A, Yanagimachi, R and Visconti, PE (2013). Ca2+ ionophore A23187 can make mouse spermatozoa capable of fertilizing in vitro without activation of cAMP-dependent phosphorylation pathways. Proc Natl Acad Sci USA 110, 18543–8.CrossRefGoogle ScholarPubMed
van Wissen, B, Bomsel-Helmreich, O and Frydman, R (1995). Sperm–zona binding and sperm-oocyte penetration analysed by DNA fluorescence: a test for gamete quality after in- vitro fertilization. Hum Reprod 10, 3218–25.CrossRefGoogle ScholarPubMed
Vargas, A, Bustos-Obregon, E and Hartley, R (2011). Effects of hypoxia on epididymal sperm parameters and protective role of ibuprofen and melatonin. Biol Res 44, 161–7.CrossRefGoogle ScholarPubMed
Verratti, V, Di Giulio, C, D’Angeli, A, Tafuri, A, Francavilla, S and Pelliccione, F (2016). Sperm forward motility is negatively affected by short-term exposure to altitude hypoxia. Andrologia 48, 800–6.CrossRefGoogle ScholarPubMed
Wang, G, Li, Y, Yang, Q, Xu, S, Ma, S, Yan, R, Zhang, R, Jia, G, Ai, D and Yang, Q (2019a). Gene expression dynamics during the gonocyte to spermatogonia transition and spermatogenesis in the domestic yak. J Anim Sci Biotechnol 10, 64.CrossRefGoogle ScholarPubMed
Wang, SY, Lau, K, Lai, KP, Zhang, JW, Tse, AC, Li, JW, Tong, Y, Chan, TF, Wong, CK, Chiu, JM, Au, DW, Wong, AS, Kong, RY and Wu, RS (2016). Hypoxia causes transgenerational impairments in reproduction of fish. Nat Commun 7, 12114.CrossRefGoogle ScholarPubMed
Wang, YJ, Jia, GX, Yan, RG, Guo, SC, Tian, F, Ma, JB, Zhang, RN, Li, C, Zhang, LZ, Du, YR and Yang, QE (2019b). Testosterone-retinoic acid signaling directs spermatogonial differentiation and seasonal spermatogenesis in the Plateau pika (Ochotona curzoniae). Theriogenology 123, 74–82.CrossRefGoogle Scholar
Watkins, AJ, Dias, I, Tsuro, H, Allen, D, Emes, RD, Moreton, J, Wilson, R, Ingram, RJM and Sinclair, KD (2018). Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proc Natl Acad Sci USA 115, 10064–9.CrossRefGoogle ScholarPubMed
Weyrich, A, Lenz, D, Jeschek, M, Chung, TH, Rübensam, K, Göritz, F, Jewgenow, K and Fickel, J (2016). Paternal intergenerational epigenetic response to heat exposure in male wild guinea pigs. Mol Ecol 25, 1729–40.CrossRefGoogle ScholarPubMed
Wu, X and Zhang, Y (2017). TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18, 517–34.CrossRefGoogle ScholarPubMed
Yan, RG, Li, BY and Yang, QE (2020). Function and transcriptomic dynamics of Sertoli cells during prospermatogonia development in mouse testis. Reprod Biol 20, 525–35.CrossRefGoogle ScholarPubMed
Zhang, W, Yang, J, Lv, Y, Li, S and Qiang, M (2019). Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1–2 male offspring. Chemosphere 228, 586–94.CrossRefGoogle ScholarPubMed
Zhao, Y, Lu, X, Cheng, Z, Tian, M, Qiangba, Y, Fu, Q and Ren, Z (2019). Comparative proteomic analysis of Tibetan pig spermatozoa at high and low altitudes. BMC Genom 20, 569.CrossRefGoogle ScholarPubMed
Zheng, S, Liu, Y, Li, P and Tian, H (2019). Short-term high-altitude exposure (3600 m) alters the type distribution of sperm deformity. High Alt Med Biol 20, 198–202.CrossRefGoogle ScholarPubMed
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