Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility

Liping Cheng , He Jin , Tianheng Xiao , Xiaoyu Yang , Tingting Zhao , Eugene Yujun Xu

Journal of Biomedical Research ›› 2024, Vol. 38 ›› Issue (5) : 473 -484.

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Journal of Biomedical Research ›› 2024, Vol. 38 ›› Issue (5) :473 -484. DOI: 10.7555/JBR.37.20230296
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Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility
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Abstract

Reliable molecular biomarkers to predict fertility remain scarce. The current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm quality. Using reverse transcription-PCR and real-time reverse transcription-PCR assays, we identified seven circular RNAs from the human BOULE gene in human sperm. We observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia, while the expression levels of both circEx2-6 and circEx2-7 were decreased in teratozoospermia, compared with the controls. Furthermore, we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm DNA fragmentation index, and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive technologies. Further functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male fertility. Collectively, our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA quality. Therefore, clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.

Keywords

human circBOULE RNAs / sperm DNA fragmentation index / fertilization rate / cleavage rate / semen parameters / assisted reproductive technology

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Liping Cheng, He Jin, Tianheng Xiao, Xiaoyu Yang, Tingting Zhao, Eugene Yujun Xu. Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility. Journal of Biomedical Research, 2024, 38(5): 473-484 DOI:10.7555/JBR.37.20230296

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Fundings

This work was supported by the National Natural Science Foundation of China (Grant Nos. 31970792 and 31771652).

Acknowledgments

We thank Dr. Liuze Gao and Wenjuan Xia for their efforts in the early stage of this project and thank Chenwang Zhang for his comments on the manuscript.

References

[1]

Cannarella R, Condorelli RA, Duca Y, et al. New insights into the genetics of spermatogenic failure: a review of the literature[J]. Hum Genet, 2019, 138(2): 125-140. doi: 10.1007/s00439-019-01974-1

[2]

Sakkas D, Ramalingam M, Garrido N, et al. Sperm selection in natural conception: what can we learn from Mother Nature to improve assisted reproduction outcomes[J]. Hum Reprod Update, 2015, 21(6): 711-726. doi: 10.1093/humupd/dmv042

[3]

Sousa AP, Amaral A, Baptista M, et al. Not all sperm are equal: functional mitochondria characterize a subpopulation of human sperm with better fertilization potential[J]. PLoS One, 2011, 6(3): e18112. doi: 10.1371/journal.pone.0018112

[4]

Chen L, Yang L. Regulation of circRNA biogenesis[J]. RNA Biol, 2015, 12(4): 381-388. doi: 10.1080/15476286.2015.1020271

[5]

Miller D, Ostermeier GC, Krawetz SA. The controversy, potential and roles of spermatozoal RNA[J]. Trends Mol Med, 2005, 11(4): 156-163. doi: 10.1016/j.molmed.2005.02.006

[6]

Jodar M, Kalko S, Castillo J, et al. Differential RNAs in the sperm cells of asthenozoospermic patients[J]. Hum Reprod, 2012, 27(5): 1431-1438. doi: 10.1093/humrep/des021

[7]

Platts AE, Dix DJ, Chemes HE, et al. Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs[J]. Hum Mol Genet, 2007, 16(7): 763-773. doi: 10.1093/hmg/ddm012

[8]

Montjean D, De La Grange P, Gentien D, et al. Sperm transcriptome profiling in oligozoospermia[J]. J Assist Reprod Genet, 2012, 29(1): 3-10. doi: 10.1007/s10815-011-9644-3

[9]

García-Herrero S, Garrido N, Martínez-Conejero JA, et al. Ontological evaluation of transcriptional differences between sperm of infertile males and fertile donors using microarray analysis[J]. J Assist Reprod Genet, 2010, 27(2-3): 111-120. doi: 10.1007/s10815-010-9388-5

[10]

Garrido N, Martínez-Conejero JA, Jauregui J, et al. Microarray analysis in sperm from fertile and infertile men without basic sperm analysis abnormalities reveals a significantly different transcriptome[J]. Fertil Steril, 2009, 91(4 Suppl): 1307-1310. doi: 10.1016/j.fertnstert.2008.01.078

[11]

Nguyen MT, Delaney DP, Kolon TF. Gene expression alterations in cryptorchid males using spermatozoal microarray analysis[J]. Fertil Steril, 2009, 92(1): 182-187. doi: 10.1016/j.fertnstert.2008.05.043

[12]

Caballero-Campo P, Lira-Albarrán S, Barrera D, et al. Gene transcription profiling of astheno- and normo-zoospermic sperm subpopulations[J]. Asian J Androl, 2020, 22(6): 608-615. doi: 10.4103/aja.aja_143_19

[13]

Zhang Z, Yang T, Xiao J. Circular RNAs: promising biomarkers for human diseases[J]. EBioMedicine, 2018, 34: 267-274. doi: 10.1016/j.ebiom.2018.07.036

[14]

Chioccarelli T, Manfrevola F, Porreca V, et al. The cannabinoid receptor CB1 stabilizes sperm chromatin condensation status during epididymal transit by promoting disulphide bond formation[J]. Int J Mol Sci, 2020, 21(9): 3117. doi: 10.3390/ijms21093117

[15]

Manfrevola F, Chioccarelli T, Cobellis G, et al. CircRNA role and circRNA-dependent network (ceRNET) in asthenozoospermia[J]. Front Endocrinol (Lausanne), 2020, 11: 395. doi: 10.3389/fendo.2020.00395

[16]

Ragusa M, Barbagallo D, Chioccarelli T, et al. CircNAPEPLD is expressed in human and murine spermatozoa and physically interacts with oocyte miRNAs[J]. RNA Biol, 2019, 16(9): 1237-1248. doi: 10.1080/15476286.2019.1624469

[17]

Dong W, Li H, Qing X, et al. Identification and characterization of human testis derived circular RNAs and their existence in seminal plasma[J]. Sci Rep, 2016, 6: 39080. doi: 10.1038/srep39080

[18]

Shah C, VanGompel MJW, Naeem V, et al. Widespread presence of human BOULE homologs among animals and conservation of their ancient reproductive function[J]. PLoS Genet, 2010, 6(7): e1001022. doi: 10.1371/journal.pgen.1001022

[19]

Xu EY, Moore FL, Pera RAR. A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans[J]. Proc Natl Acad Sci U S A, 2001, 98(13): 7414-7419. doi: 10.1073/pnas.131090498

[20]

Eberhart CG, Maines JZ, Wasserman SA. Meiotic cell cycle requirement for a fly homologue of human Deleted in azoospermia[J]. Nature, 1996, 381(6585): 783-785. doi: 10.1038/381783a0

[21]

Gao L, Chang S, Xia W, et al. Circular RNAs from BOULE play conserved roles in protection against stress-induced fertility decline[J]. Sci Adv, 2020, 6(46): eabb7426. doi: 10.1126/sciadv.abb7426

[22]

World Health Organization. WHO laboratory manual for the examination and processing of human semen[M]. 5th ed. Geneva: World Health Organization, 2010.

[23]

Lambard S, Galeraud-Denis I, Martin G, et al. Analysis and significance of mRNA in human ejaculated sperm from normozoospermic donors: relationship to sperm motility and capacitation[J]. Mol Hum Reprod, 2004, 10(7): 535-541. doi: 10.1093/molehr/gah064

[24]

Goodrich R, Johnson G, Krawetz SA. The preparation of human spermatozoal RNA for clinical analysis[J]. Arch Androl, 2007, 53(3): 161-167. doi: 10.1080/01485010701216526

[25]

Liu C, Chen L. Circular RNAs: characterization, cellular roles, and applications[J]. Cell, 2022, 185(12): 2016-2034. doi: 10.1016/j.cell.2022.04.021

[26]

Varghese AC, Bragais FM, Mukhopadhyay D, et al. Human sperm DNA integrity in normal and abnormal semen samples and its correlation with sperm characteristics[J]. Andrologia, 2009, 41(4): 207-215. doi: 10.1111/j.1439-0272.2009.00917.x

[27]

Derijck AAHA, Van Der Heijden GW, Ramos L, et al. Motile human normozoospermic and oligozoospermic semen samples show a difference in double-strand DNA break incidence[J]. Hum Reprod, 2007, 22(9): 2368-2376. doi: 10.1093/humrep/dem166

[28]

Borini A, Tarozzi N, Bizzaro D, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART[J]. Hum Reprod, 2006, 21(11): 2876-2881. doi: 10.1093/humrep/del251

[29]

Muriel L, Goyanes V, Segrelles E, et al. Increased aneuploidy rate in sperm with fragmented DNA as determined by the sperm chromatin dispersion (SCD) test and FISH analysis[J]. J Androl, 2007, 28(1): 38-49. doi: 10.2164/jandrol.106.000067

[30]

Venkatesh S, Singh A, Shamsi MB, et al. Clinical significance of sperm DNA damage threshold value in the assessment of male infertility[J]. Reprod Sci, 2011, 18(10): 1005-1013. doi: 10.1177/1933719111401662

[31]

Giwercman A, Richthoff J, Hjøllund H, et al. Correlation between sperm motility and sperm chromatin structure assay parameters[J]. Fertil Steril, 2003, 80(6): 1404-1412. doi: 10.1016/S0015-0282(03)02212-X

[32]

Moskovtsev SI, Willis J, Azad A, et al. Sperm DNA integrity: correlation with sperm plasma membrane integrity in semen evaluated for male infertility[J]. Arch Androl, 2005, 51(1): 33-40. doi: 10.1080/014850190512770

[33]

Sendler E, Johnson GD, Mao S, et al. Stability, delivery and functions of human sperm RNAs at fertilization[J]. Nucleic Acids Res, 2013, 41(7): 4104-4117. doi: 10.1093/nar/gkt132

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