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Detection of aberrant DNA methylation patterns in sperm of male recurrent spontaneous abortion patients

Published online by Cambridge University Press:  09 January 2023

Rong-Hua Ma
Affiliation:
Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China Center for Plateau Medicine Research, Qinghai University, Xining, Qinghai, China
Zhen-Gang Zhang
Affiliation:
Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Yong-Tian Zhang
Affiliation:
Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Sheng-Yan Jian
Affiliation:
Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China
Bin-Ye Li*
Affiliation:
Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China
*
Author for correspondence: Bin-Ye Li, Center for Reproductive Medicine, Qinghai Provincial People’s Hospital, Xining, Qinghai, China. E-mail: qhsrmyylby@foxmail.com

Summary

Aberrant DNA methylation patterns in sperm are a cause of embryonic failure and infertility, and could be a critical factor contributing to male recurrent spontaneous abortion (RSA). The purpose of this study was to reveal the potential effects of sperm DNA methylation levels in patients with male RSA. We compared sperm samples collected from fertile men and oligoasthenospermia patients. Differentially methylated sequences were identified by reduced representation bisulfite sequencing (RRBS) methods. The DNA methylation levels of the two groups were compared and qRT-PCR was used to validate the expression of genes showing differential methylation. The results indicated that no difference in base distribution was observed between the normal group and the patient group. However, the chromosome methylation in these two groups was markedly different. One site was located on chromosome 8 and measured 150 bp, while the other sites were on chromosomes 9, 10, and X and measured 135 bp, 68 bp, and 136 bp, respectively. In particular, two genes were found to be hypermethylated in these patients, one gene was DYDC2 (placed in the differential methylation region of chromosome 10), and the other gene was NXF3 (located on chromosome X). Expression levels of DYDC2 and NXF3 in the RSA group were significantly lower than those in the normal group (P < 0.05). Collectively, these results demonstrated that changes in DNA methylation might be related to male RSA. Our findings provide important information regarding the potential role of sperm DNA methylation in human development.

Type
Research Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press

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References

Ahmadi, A. and Ng, S. C. (1999). Developmental capacity of damaged spermatozoa. Human Reproduction, 14(9), 22792285. doi: 10.1093/humrep/14.9.2279 CrossRefGoogle ScholarPubMed
Aliakbari, F., Taghizabet, N., Azizi, F., Rezaei-Tazangi, F., Samadee Gelehkolaee, K. and Kharazinejad, E. (2022). A review of methods for preserving male fertility. Zygote, 30(3), 289297. doi: 10.1017/S0967199421000071 CrossRefGoogle ScholarPubMed
Argyraki, M., Damdimopoulou, P., Chatzimeletiou, K., Grimbizis, G. F., Tarlatzis, B. C., Syrrou, M. and Lambropoulos, A. (2019). In-utero stress and mode of conception: Impact on regulation of imprinted genes, fetal development and future health. Human Reproduction Update, 25(6), 777801. doi: 10.1093/humupd/dmz025 CrossRefGoogle ScholarPubMed
Asgari, F., Gavahi, A., Karimi, M., Vatannejad, A., Amjadi, F., Aflatoonian, R. and Zandieh, Z. (2021). Risk of embryo aneuploidy is affected by the increase in sperm DNA damage in recurrent implantation failure patients under ICSI-CGH array cycles. Human Fertility (Camb), 19. doi: 10.1080/14647273.2021.1920054 Google ScholarPubMed
Barlow, D. P. and Bartolomei, M. S. (2014). Genomic imprinting in mammals. Cold Spring Harbor Perspectives in Biology, 6(2), a018382. doi: 10.1101/cshperspect.a018382 CrossRefGoogle ScholarPubMed
Bestor, T. H. (2000). The DNA methyltransferases of mammals. Human Molecular Genetics, 9(16), 23952402. doi: 10.1093/hmg/9.16.2395 CrossRefGoogle ScholarPubMed
Burlibaşa, L., Nicu, A. T. and Domnariu, C. (2021). DNA methyltransferase inhibitors modulate histone methylation: Epigenetic crosstalk between H3K4me3 and DNA methylation during sperm differentiation. Zygote, 29(3), 239244. doi: 10.1017/S0967199420000684 CrossRefGoogle ScholarPubMed
Cannarella, R., Crafa, A., Condorelli, R. A., Mongioì, L. M., La Vignera, S. and Calogero, A. E. (2021). Relevance of sperm imprinted gene methylation on assisted reproductive technique outcomes and pregnancy loss: A systematic review. Systems Biology in Reproductive Medicine, 67(4), 251259. doi: 10.1080/19396368.2021.1909667 CrossRefGoogle ScholarPubMed
Coomarasamy, A., Dhillon-Smith, R. K., Papadopoulou, A., Al-Memar, M., Brewin, J., Abrahams, V. M., Maheshwari, A., Christiansen, O. B., Stephenson, M. D., Goddijn, M., Oladapo, O. T., Wijeyaratne, C. N., Bick, D., Shehata, H., Small, R., Bennett, P. R., Regan, L., Rai, R., Bourne, T., Quenby, S. (2021). Recurrent miscarriage: Evidence to accelerate action. Lancet, 397(10285), 16751682. doi: 10.1016/S0140-6736(21)00681-4 CrossRefGoogle ScholarPubMed
Elhamamsy, A. R. (2017). Role of DNA methylation in imprinting disorders: An updated review. Journal of Assisted Reproduction and Genetics, 34(5), 549562. doi: 10.1007/s10815-017-0895-5 CrossRefGoogle ScholarPubMed
Gharagozloo, P., Gutiérrez-Adán, A., Champroux, A., Noblanc, A., Kocer, A., Calle, A., Pérez-Cerezales, S., Pericuesta, E., Polhemus, A., Moazamian, A., Drevet, J. R. and Aitken, R. J. (2016). A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: Promising preclinical evidence from animal models. Human Reproduction, 31(2), 252262. doi: 10.1093/humrep/dev302 CrossRefGoogle ScholarPubMed
Gopal, R., Foster, K. W. and Yang, P. (2012). The DPY-30 domain and its flanking sequence mediate the assembly and modulation of flagellar radial spoke complexes. Molecular and Cellular Biology, 32(19), 40124024. doi: 10.1128/MCB.06602-11 CrossRefGoogle ScholarPubMed
Gunes, S. and Esteves, S. C. (2021). Role of genetics and epigenetics in male infertility. Andrologia, 53(1), e13586. doi: 10.1111/and.13586 CrossRefGoogle ScholarPubMed
He, W., Sun, ϒ., Zhang, S., Feng, X., Xu, M., Dai, J., Ni, X., Wang, X. and Wu, Q. (2020). Profiling the DNA methylation patterns of imprinted genes in abnormal semen samples by next-generation bisulfite sequencing. Journal of Assisted Reproduction and Genetics, 37(9), 22112221. doi: 10.1007/s10815-020-01839-x CrossRefGoogle ScholarPubMed
Hon, G. C., Rajagopal, N., Shen, Y., McCleary, D. F., Yue, F., Dang, M. D. and Ren, B. (2013). Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nature Genetics, 45(10), 11981206. doi: 10.1038/ng.2746 CrossRefGoogle ScholarPubMed
James, E. and Jenkins, T. G. (2018). Epigenetics, infertility, and cancer: Future directions. Fertility and Sterility, 109(1), 2732. doi: 10.1016/j.fertnstert.2017.11.006 CrossRefGoogle ScholarPubMed
Jenkins, T. G., Aston, K. I., Meyer, T. D., Hotaling, J. M., Shamsi, M. B., Johnstone, E. B., Cox, K. J., Stanford, J. B., Porucznik, C. A. and Carrell, D. T. (2016). Decreased fecundity and sperm DNA methylation patterns. Fertility and Sterility, 105(1), 51–7.e1–57.e1–3. doi: 10.1016/j.fertnstert.2015.09.013 CrossRefGoogle ScholarPubMed
Klimczak, A. M., Patel, D. P., Hotaling, J. M. and Scott, R. T. (2021). Role of the sperm, oocyte, and embryo in recurrent pregnancy loss. Fertility and Sterility, 115(3), 533537. doi: 10.1016/j.fertnstert.2020.12.005 CrossRefGoogle ScholarPubMed
Krausz, C. and Riera-Escamilla, A. (2018). Genetics of male infertility. Nature Reviews. Urology, 15(6), 369384. doi: 10.1038/s41585-018-0003-3 CrossRefGoogle ScholarPubMed
Li, Y. C., Wang, G. W., Xu, S. R., Zhang, X. N. and Yang, Q. E. (2020). The expression of histone methyltransferases and distribution of selected histone methylations in testes of yak and cattle-yak hybrid. Theriogenology, 144, 164173. doi: 10.1016/j.theriogenology.2020.01.001 CrossRefGoogle ScholarPubMed
Liu, Y., Zhang, Y., Yin, J., Gao, Y., Li, Y., Bai, D., He, W., Li, X., Zhang, P., Li, R., Zhang, L., Jia, Y., Zhang, Y., Lin, J., Zheng, Y., Wang, H., Gao, S., Zeng, W. and Liu, W. (2019). Distinct H3K9me3 and DNA methylation modifications during mouse spermatogenesis. Journal of Biological Chemistry, 294(49), 1871418725. doi: 10.1074/jbc.RA119.010496 CrossRefGoogle ScholarPubMed
Livak, K. J. and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4), 402408. doi: 10.1006/meth.2001.1262 CrossRefGoogle ScholarPubMed
Lou, H., Le, F., Hu, M., Yang, X., Li, L., Wang, L., Wang, N., Gao, H. and Jin, F. (2019). Aberrant DNA methylation of IGF2-H19 locus in human fetus and in spermatozoa from assisted reproductive technologies. Reproductive Sciences, 26(7), 9971004. doi: 10.1177/1933719118802052 CrossRefGoogle ScholarPubMed
Ma, X., Zhang, S., Zhang, M., Zhu, Y., Ma, P., Yang, S., Su, L., Li, Z., Lv, W. and Luan, W. (2018). TRIM28 down-regulation on methylation imprints in bovine preimplantation embryos. Zygote, 26(6), 449456. doi: 10.1017/S0967199418000424 CrossRefGoogle ScholarPubMed
Practice Committee of the American Society for Reproductive Medicine (2020). Definitions of infertility and recurrent pregnancy loss: A committee opinion. Fertility and Sterility, 113(3), 533535. doi: 10.1016/j.fertnstert.2019.11.025 CrossRefGoogle Scholar
Quenby, S., Gallos, I. D., Dhillon-Smith, R. K., Podesek, M., Stephenson, M. D., Fisher, J., Brosens, J. J., Brewin, J., Ramhorst, R., Lucas, E. S., McCoy, R. C., Anderson, R., Daher, S., Regan, L., Al-Memar, M., Bourne, T., MacIntyre, D. A., Rai, R., Christiansen, O. B., Coomarasamy, A. (2021). Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet, 397(10285), 16581667. doi: 10.1016/S0140-6736(21)00682-6 CrossRefGoogle ScholarPubMed
Rajender, S., Avery, K. and Agarwal, A. (2011). Epigenetics, spermatogenesis and male infertility. Mutation Research, 727(3), 6271. doi: 10.1016/j.mrrev.2011.04.002 CrossRefGoogle ScholarPubMed
Rodrigo, L. (2020). Sperm genetic abnormalities and their contribution to embryo aneuploidy & miscarriage. Best Practice & Research Clinical Endocrinology & Metabolism, 34, 101477. doi: 10.1016/j.beem.2020.101477 CrossRefGoogle ScholarPubMed
Sakkas, D., Ramalingam, M., Garrido, N. and Barratt, C. L. R. (2015). Sperm selection in natural conception: What can we learn from Mother Nature to improve assisted reproduction outcomes? Human Reproduction Update, 21(6), 711726. doi: 10.1093/humupd/dmv042 CrossRefGoogle ScholarPubMed
Tournaye, H., Krausz, C. and Oates, R. D. (2017). Novel concepts in the aetiology of male reproductive impairment. Lancet. Diabetes and Endocrinology, 5(7), 544553. doi: 10.1016/S2213-8587(16)30040-7 CrossRefGoogle ScholarPubMed
Uysal, F., Akkoyunlu, G. and Ozturk, S. (2016). DNA methyltransferases exhibit dynamic expression during spermatogenesis. Reproductive Biomedicine Online, 33(6), 690702. doi: 10.1016/j.rbmo.2016.08.022 CrossRefGoogle ScholarPubMed
Weber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M. and Schübeler, D. (2007). Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nature Genetics, 39(4), 457466. doi: 10.1038/ng1990 CrossRefGoogle ScholarPubMed
Yin, Y., Wang, G., Liang, N., Zhang, H., Liu, Z., Li, W. and Sun, F. (2013). Nuclear export factor 3 is involved in regulating the expression of TGF-β3 in an mRNA export activity-independent manner in mouse Sertoli cells. Biochemical Journal, 452(1), 6778. doi: 10.1042/BJ20121006 CrossRefGoogle Scholar
Yuan, M., Huang, L., Leung, W. T., Wang, M., Meng, Y., Huang, Z., Pan, X., Zhou, J., Li, C., Sima, Y., Wang, L., Zhang, Y., Ying, C. and Wang, L. (2019). Sperm DNA fragmentation valued by SCSA and its correlation with conventional sperm parameters in male partner of recurrent spontaneous abortion couple. BioScience Trends, 13(2), 152159. doi: 10.5582/bst.2018.01292 CrossRefGoogle ScholarPubMed
Zhang, X., Wang, H., Feng, T., Yang, J., Huang, Q., Lu, C., Guan, Y., Sun, R., Chen, M. and Qian, Y. (2020a). The relationship between semen factors and unexplained recurrent spontaneous abortion. Clinica Chimica Acta; International Journal of Clinical Chemistry, 510, 605612. doi: 10.1016/j.cca.2020.08.022 CrossRefGoogle ScholarPubMed
Zhang, X., Wang, Y., Zhao, N., Liu, P. and Huang, J. (2020b). Variations in chromosomal aneuploidy rates in IVF blastocysts and early spontaneous abortion chorionic villi. Journal of Assisted Reproduction and Genetics, 37(3), 527537. doi: 10.1007/s10815-019-01682-9 CrossRefGoogle ScholarPubMed
Zhou, Q., Xiong, Y., Qu, B., Bao, A. and Zhang, Y. (2021). DNA methylation and recurrent pregnancy loss: A mysterious compass? Frontiers in Immunology, 12, 738962. doi: 10.3389/fimmu.2021.738962 CrossRefGoogle Scholar