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RESEARCH ARTICLE
Contents Vol 36(4)

Lycopene inhibits apoptosis of mouse spermatocytes in varicocele via miR-23a/b-induced downregulation of PROK2

Hongqiang Wang A , Baojuan Zhu B , Tao Jing A , Lei Yu A , Kaishu Zhang A , Yujie Liu A and Hanshu Wang https://orcid.org/0000-0002-9996-5114 A *
+ Author Affiliations
- Author Affiliations

A Department of Andrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao, Shandong Province 266000, China.

B Department of Hemodialysis Room, Nephrology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao, Shandong Province 266000, China.

* Correspondence to: wanghanshu@qdu.edu.cn

Handling Editor: Jessica Dunleavy

Reproduction, Fertility and Development 36, RD23136 https://doi.org/10.1071/RD23136
Submitted: 30 July 2023  Accepted: 15 January 2024  Published online: 2 February 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing

Abstract

Context

The varicocele is the leading cause of male infertility and can impair sperm quality and testicular function through various mechanisms. In our previous study, we found that lycopene could attenuate hypoxia-induced testicular injury.

Aims

To illustrate the detailed mechanism of lycopene on spermatocytes.

Methods

The effect of lycopene on GC-2 cells under hypoxia were detected by flow cytometry and western blot assay. miR-seq was used to determine miRNA expression in varicocele rat model testes. The function of miR-23a/b were determined by flow cytometry and western blot assay.

Key results

We demonstrate that lycopene could alleviate hypoxia-induced GC-2 cell apoptosis and could elevate miR-23a/b expression of the hypoxia model in vivo and in vitro. The miR-23a and -23b mimics could reduce the hypoxia-induced GC-2 cell apoptosis. Both miR-23a and -23b could directly bind with prokineticin 2 (PROK2) mRNA and downregulate its expression.

Conclusions

Lycopene could attenuate hypoxia-induced spermatocyte injury through the miR-23a/b–PROK2 pathway.

Implications

Lycopene may be an effective treatment for varicocele to improve testicular impairment.

Keywords: apoptosis, GC-2 cell, hypoxia, lycopene, miR-23a, miR-23b, PROK2, varicocele.

References

Abu-Halima M, Ayesh BM, Hart M, Alles J, Fischer U, Hammadeh M, Keller A, Huleihel M, Meese E (2019) Differential expression of miR-23a/b-3p and its target genes in male patients with subfertility. Fertility and Sterility 112(2), 323-335.e2.
| Crossref | Google Scholar | PubMed |

Abu-Halima M, Belkacemi A, Ayesh BM, Simone Becker L, Sindiani AM, Fischer U, Hammadeh M, Keller A, Meese E (2021) MicroRNA-targeting in spermatogenesis: over-expressions of microRNA-23a/b-3p and its affected targeting of the genes ODF2 and UBQLN3 in spermatozoa of patients with oligoasthenozoospermia. Andrology 9(4), 1137-1144.
| Google Scholar | PubMed |

Ali Syeda Z, Langden SSS’, Munkhzul C, Lee M, Song SJ (2020) Regulatory mechanism of microRNA expression in cancer. International Journal of Molecular Sciences 21(5), 1723.
| Crossref | Google Scholar |

Babaei A, Asadpour R, Mansouri K, Sabrivand A, Kazemi-Darabadi S (2022) Lycopene improves testicular damage and sperm quality in experimentally induced varicocele: relationship with apoptosis, hypoxia, and hyperthermia. Food Science & Nutrition 10(5), 1469-1480.
| Crossref | Google Scholar | PubMed |

Buchold GM, Coarfa C, Kim J, Milosavljevic A, Gunaratne PH, Matzuk MM (2010) Analysis of microRNA expression in the prepubertal testis. PLoS ONE 5(12), e15317.
| Crossref | Google Scholar | PubMed |

Cannarella R, Calogero AE, Condorelli RA, Giacone F, Mongioi’ LM, La Vignera S (2019) Non-hormonal treatment for male infertility: the potential role of serenoa repens, selenium and lycopene. European Review for Medical and Pharmacological Sciences 23(7), 3112-3120.
| Crossref | Google Scholar | PubMed |

Chiba K, Fujisawa M (2016) Clinical outcomes of varicocele repair in infertile men: a review. The World Journal of Men’s Health 34(2), 101-109.
| Crossref | Google Scholar | PubMed |

Fang Y, Su Y, Xu J, Hu Z, Zhao K, Liu C, Zhang H (2021) Varicocele-mediated male infertility: from the perspective of testicular immunity and inflammation. Frontiers in Immunology 12, 729539.
| Crossref | Google Scholar | PubMed |

Freni J, Pallio G, Marini HR, Micali A, Irrera N, Romeo C, Puzzolo D, Mannino F, Minutoli L, Pirrotta I, Scarfone A, Antonuccio P (2023) Positive effects of the nutraceutical association of lycopene and selenium in experimental varicocele. International Journal of Molecular Sciences 24(17), 13526.
| Crossref | Google Scholar |

Ghandehari-Alavijeh R, Tavalaee M, Zohrabi D, Foroozan-Broojeni S, Abbasi H, Nasr-Esfahani MH (2019) Hypoxia pathway has more impact than inflammation pathway on etiology of infertile men with varicocele. Andrologia 51(2), e13189.
| Crossref | Google Scholar | PubMed |

Iftikhar A, Akhtar MF, Saleem A, Riaz A, Zehravi M, Rahman MH, Md Ashraf G (2022) Comparative potential of zinc sulfate, L-Carnitine, lycopene, and coenzyme Q10 on cadmium-induced male infertility. International Journal of Endocrinology 2022, 6266613.
| Crossref | Google Scholar |

Iqbal MA, Arora S, Prakasam G, Calin GA, Syed MA (2019) MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance. Molecular Aspects of Medicine 70, 3-20.
| Crossref | Google Scholar | PubMed |

Jensen CFS, Østergren P, Dupree JM, Ohl DA, Sønksen J, Fode M (2017) Varicocele and male infertility. Nature Reviews Urology 14(9), 523-533.
| Crossref | Google Scholar | PubMed |

Kabekkodu SP, Shukla V, Varghese VK, D’ Souza J, Chakrabarty S, Satyamoorthy K (2018) Clustered miRNAs and their role in biological functions and diseases. Biological Reviews 93(4), 1955-1986.
| Crossref | Google Scholar | PubMed |

Kang C, Punjani N, Lee RK, Li PS, Goldstein M (2022) Effect of varicoceles on spermatogenesis. Seminars in Cell & Developmental Biology 121, 114-124.
| Crossref | Google Scholar | PubMed |

Kathrins M (2017) The varicocele as related to fertility. Fertility and Sterility 107(1), 72-73.
| Crossref | Google Scholar | PubMed |

Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nature Reviews Genetics 11(9), 597-610.
| Crossref | Google Scholar | PubMed |

Li Y, Zhou T, Su Y-F, Hu Z-Y, Wei J-J, Wang W, Liu C-Y, Zhao K, Zhang H-P (2020) Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats. Asian Journal of Andrology 22(5), 500-506.
| Crossref | Google Scholar | PubMed |

Li N, Wu X, Zhuang W, Xia L, Chen Y, Wu C, Rao Z, Du L, Zhao R, Yi M, Wan Q, Zhou Y (2021a) Tomato and lycopene and multiple health outcomes: umbrella review. Food Chemistry 343, 128396.
| Crossref | Google Scholar | PubMed |

Li Z, Wang S, Gong C, Hu Y, Liu J, Wang W, Chen Y, Liao Q, He B, Huang Y, Luo Q, Zhao Y, Xiao Y (2021b) Effects of environmental and pathological hypoxia on male fertility. Frontiers in Cell and Developmental Biology 9, 725933.
| Crossref | Google Scholar | PubMed |

Li L, Zhang X, Ren H, Huang X, Shen T, Tang W, Dou L, Li J (2022) miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas. Journal of Molecular Endocrinology 68(1), 35-49.
| Crossref | Google Scholar | PubMed |

Maldonado-Pérez D, Evans J, Denison F, Millar RP, Jabbour HN (2007) Potential roles of the prokineticins in reproduction. Trends in Endocrinology & Metabolism 18(2), 66-72.
| Crossref | Google Scholar | PubMed |

Petrella C, Spaziani M, D’Orazi V, Tarani L, Terracina S, Tarani F, Micangeli G, Barbato C, Minni A, Greco A, Isidori AM, Ferraguti G, Fiore M (2022) Prokineticin 2/PROK2 and male infertility. Biomedicines 10(10), 2389.
| Crossref | Google Scholar |

Przybylska S, Tokarczyk G (2022) Lycopene in the prevention of cardiovascular diseases. International Journal of Molecular Sciences 23(4), 1957.
| Crossref | Google Scholar |

Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH (2019) An overview of microRNAs: biology, functions, therapeutics, and analysis methods. Journal of Cellular Physiology 234(5), 5451-5465.
| Crossref | Google Scholar | PubMed |

Sethi S, Mehta P, Pandey A, Gupta G, Rajender S (2022) miRNA profiling of major testicular germ cells identifies stage-specific regulators of spermatogenesis. Reproductive Sciences 29(12), 3477-3493.
| Crossref | Google Scholar | PubMed |

Wang H, Zhu B, Yu L, Li Q, Li S, Wang P, Jing T, Men T (2021) Lycopene attenuates hypoxia-induced testicular injury by inhibiting PROK2 expression and activating PI3K/AKT/mTOR pathway in a varicocele adult rat. Evidence-based Complementary and Alternative Medicine : eCAM 2021, 3471356.
| Crossref | Google Scholar | PubMed |

Wang Y, Ping Z, Gao H, Liu Z, Xv Q, Jiang X, Yu W (2023) LYC inhibits the AKT signaling pathway to activate autophagy and ameliorate TGFB-induced renal fibrosis. Autophagy 1-20.
| Crossref | Google Scholar |

Zhai L-L, Tang Z-G (2020) Lycopene improves sperm quality: a promising nutrient for the treatment of male infertility. Phytotherapy Research 34(6), 1187-1188.
| Crossref | Google Scholar | PubMed |

Zhang S, An X, Huang S, Zeng L, Xu Y, Su D, Qu Y, Tang X, Ma J, Yang J, Ai J (2021) AhR/miR-23a-3p/PKCα axis contributes to memory deficits in ovariectomized and normal aging female mice. Molecular Therapy - Nucleic Acids 24, 79-91.
| Crossref | Google Scholar | PubMed |

Zhao Y, Li X-N, Zhang H, Cui J-G, Wang J-X, Chen M-S, Li J-L (2022) Phthalate-induced testosterone/androgen receptor pathway disorder on spermatogenesis and antagonism of lycopene. Journal of Hazardous Materials 439, 129689.
| Crossref | Google Scholar | PubMed |

Zhao Y, Chen M-S, Wang J-X, Cui J-G, Zhang H, Li X-N, Li J-L (2023) Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders. Journal of Advanced Research 49, 115-126.
| Crossref | Google Scholar | PubMed |