Effects of streptozotocin on spermatogenic function and testicular m6A methylase expression in diabetic mice

Meng Xingqi, Deng Jing, Peng Lixuan, Zhang Yuan, Lin Yi, Zhou Xiaobing, Cao Wenyu, Li Suyun

Chinese Journal of Clinical Anatomy ›› 2023, Vol. 41 ›› Issue (2) : 182-186.

PDF(2250 KB)
PDF(2250 KB)
Chinese Journal of Clinical Anatomy ›› 2023, Vol. 41 ›› Issue (2) : 182-186. DOI: 10.13418/j.issn.1001-165x.2023.2.11

Effects of streptozotocin on spermatogenic function and testicular m6A methylase expression in diabetic mice

  • Meng Xingqi 1, Deng Jing 2,  Peng Lixuan 1, Zhang Yuan 3, Lin Yi 3, Zhou Xiaobing 1, Cao Wenyu 1*, Li Suyun1*
Author information +
History +

Abstract

Objective    To investigate the effects of streptozotocin (STZ) on spermatogenic function and testicular m6A methylase expression in diabetic mice.    Methods   Twenty 8-week-old male ICR mice were randomly divided into a vehicle control group (NS) and a model group (STZ), and an animal model of diabetes was induced by intraperitoneal injection of STZ. Blood glucose and body weight changes were measured on the 2nd, 4th, 6th, 8th week after STZ injection. On the 8th week, testes and epididymis were weighed and the number of sperm was also counted, HE staining was then used to detect sperm motility and testicular morphology changes. Real-time PCR and Western blotting methods were used to detect the expression level of m6A methylase mRNA and protein in the testis of each group of mice.    Results   Compared with the NS group, the fasting blood glucose was significantly increased and body weight was significantly decreased in the model group (P<0.01), the weight of the testis and epididymis was significantly decreased (P<0.01), and the number of sperm was significantly decreased (P<0.05); the morphological structure of the testis was destroyed, the seminiferous tubules shrinked, the diameter of the lumen became smaller, the arrangement of spermatogenic cells at all levels was disordered, and the number of sperm in the lumen decreased; the expression of testicular m6A methylases METTL3, FTO, and YTHDF3 mRNA were significantly decreased (P<0.05); the expression of METTL3 and FTO protein were significantly reduced (P<0.05).    Conclusions   The spermatogenesis disorder in STZ-induced diabetic mice may be related to the abnormal expression of m6A methylase METTL3 and FTO in the testis.

Key words

m6A methylation;  /   / Streptozotocin;  /   / Diabetes;  /   /  Spermatogenic dysfunction

Cite this article

Download Citations
Meng Xingqi, Deng Jing, Peng Lixuan, Zhang Yuan, Lin Yi, Zhou Xiaobing, Cao Wenyu, Li Suyun. Effects of streptozotocin on spermatogenic function and testicular m6A methylase expression in diabetic mice[J]. Chinese Journal of Clinical Anatomy. 2023, 41(2): 182-186 https://doi.org/10.13418/j.issn.1001-165x.2023.2.11

References

[1] Ndjaboue R, Farhat I, Ferlatte CA, et al. Predictive models of diabetes complications: protocol for a scoping review[J]. Syst Rev, 2020, 9(1): 137. DOI: 10.1186/s13643-020-01391-w.
[2]  La Vignera S, Condorelli R, Vicari E, et al. Diabetes mellitus and sperm parameters[J]. J Androl, 2012, 33(2): 145-153. DOI: 10.2164/jandrol.111.013193.
[3]  Kleinberger JW, Pollin TI. Personalized medicine in diabetes mellitus: current opportunities and future prospects[J]. Ann N Y Acad Sci, 2015, 1346(1): 45-56. DOI: 10.1111/nyas.12757.
[4]  Qin Y, Li L, Luo E, et al. Role of m6A RNA methylation in cardiovascular disease (Review)[J]. Int J Mol Med, 2020, 46(6): 1958-1972. DOI: 10.3892/ijmm.2020.4746.
[5] Widagdo J, Anggono V. The m6A-epitranscriptomic signature in neurobiology: from neurodevelopment to brain plasticity[J]. J Neurochem, 2018, 147(2): 137-152. DOI: 10.1111/jnc.14481.
[6]  Wu S, Zhang S, Wu X, et al. m(6)A RNA methylation in cardiovascular diseases[J]. Mol Ther, 2020, 28(10): 2111-2119. DOI: 10.1016/j.ymthe.2020.08.010.
[7]  Wu J, Frazier K, Zhang J, et al. Emerging role of m(6)A RNA methylation in nutritional physiology and metabolism[J]. Obes Rev, 2020, 21(1): e12942. DOI: 10.1111/obr.12942.
[8]  杨润军, 李青旺, 赵蕊. 四氧嘧啶与链脲佐菌素诱导小鼠糖尿病模型的效果比较[J]. 西北农林科技大学学报(自然科学版), 2006, 34(2): 17-20. DOI: 10.13207/j.cnki.jnwafu.2006.02.004.
[9]  姚兰, 蒋成霞, 郭艳艳, 等. 沙棘多糖抑制PERK/ATF4/CHOP通路缓解糖尿病大鼠胰岛素抵抗和肝肾功能损伤[J]. 中国临床解剖学杂志, 2021, 39(2): 187-191. DOI: 10.13418/j.issn.1001-165x.2021.02.013.
[10]刘莉, 罗鹏, 周田田, 等. 厄贝沙坦对高血压合并2型糖尿病大鼠胰岛素抵抗IRS-1/PI3K/GLUT4信号通路的影响[J]. 中国临床解剖学杂志, 2021, 39(5): 563-568. DOI: 10.13418/j.issn.1001-165x.2021.05.012.
[11]Goyal SN, Reddy NM, Patil KR, et al. Challenges and issues with streptozotocin-induced diabetes- a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics[J]. Chem Biol Interact, 2016, 244: 49-63. DOI: 10.1016/j.cbi.2015.11.032.
[12]Saadane A, Lessieur EM, Du Y, et al. Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy[J]. PLoS One, 2020, 15(9): e0238727. DOI: 10.1371/journal.pone.0238727.
[13]Yigitturk G, Acara AC, Erbas O, et al. The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes[J]. Biomed Pharmacother, 2017, 87: 240-246. DOI: 10.1016/j.biopha.2016.12.102.
[14]Li Z, Hao S, Yin H, et al. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice[J]. Behav Brain Res, 2016, 305: 265-277. DOI: 10.1016/j.bbr.2016.03.023.
[15]Shi GJ, Zheng J, Wu J, et al. Beneficial effects of Lycium barbarum polysaccharide on spermatogenesis by improving antioxidant activity and inhibiting apoptosis in streptozotocin-induced diabetic male mice[J]. Food Funct, 2017, 8(3): 1215-1226. DOI: 10.1039/c6fo01575a.
[16]邱竹, 姜蓉, 汪子铃, 等. 当归多糖对D-半乳糖致衰老小鼠睾丸的保护作用[J]. 解剖学报, 2019, 50(4): 506-511. DOI: 10.16098/j.issn.0529-1356.2019.04.017.
[17]牛磊, 罗诗诗, 李威, 等. 丰富环境通过抑制NOD样受体蛋白3炎性小体活化缓解脂多糖小鼠的认知障碍[J]. 解剖学报, 2020, 51(2): 172-177. DOI: 10.16098/j.issn.0529-1356.2020.02.004.
[18]罗诗诗, 苏强, 孙秋敏, 等. 小鼠视觉发育关键期外侧膝状体胰岛素样生长因子2的动态表达[J]. 解剖学报, 2020, 51(3): 338-343. DOI: 10.16098/j.issn.0529-1356.2020.03.005.
[19]Pergialiotis V, Prodromidou A, Frountzas M, et al. Diabetes mellitus and functional sperm characteristics: a meta-analysis of observational studies[J]. J Diabetes Complications, 2016, 30(6): 1167-1176. DOI: 10.1016/j.jdiacomp.2016.04.002.
[20]罗丹, 杨惠, 罗诗诗, 等. 海马sortilin在链脲佐菌素诱导的糖尿病认知损伤小鼠中的作用[J]. 解剖学报, 2020, 51(1): 9-14. DOI: 10.16098/j.issn.0529-1356.2020.01.002.
[21]Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal[J]. Physiol Rev, 1972, 52(1): 198-236. DOI: 10.1152/physrev.1972.52.1.198.
[22]Leonetti AM, Chu MY, Ramnaraign FO, et al. An emerging role of m6A in memory: a case for translational priming[J]. Int J Mol Sci, 2020, 21(20): 7447. DOI: 10.3390/ijms21207447.
[23]Zhang C, Fu J, Zhou Y. A review in research progress concerning m6a methylation and immunoregulation[J]. Front Immunol, 2019, 10: 922. DOI: 10.3389/fimmu.2019.00922.
[24]Yang Y, Huang W, Huang JT, et al. Increased N6-methyladenosine in human sperm RNA as a risk factor for asthenozoospermia[J]. Sci Rep, 2016, 6: 24345. DOI: 10.1038/srep24345.
[25]Xu K, Yang Y, Feng GH, et al. Mettl3-mediated m(6)A regulates spermatogonial differentiation and meiosis initiation[J]. Cell Res, 2017, 27(9): 1100-1114. DOI: 10.1038/cr.2017.100.
[26]Lin Z, Hsu PJ, Xing X, et al. Mettl3-/Mettl14-mediated mRNA N(6)-methyladenosine modulates murine spermatogenesis[J]. Cell Res, 2017, 27(10): 1216-1230. DOI: 10.1038/cr.2017.117.
[27]Landfors M, Nakken S, Fusser M, et al. Sequencing of FTO and ALKBH5 in men undergoing infertility work-up identifies an infertility-associated variant and two missense mutations[J]. Fertil Steril, 2016, 105(5): 1170-1179.e5. DOI: 10.1016/j.fertnstert.2016.01.002.
[28]Li A, Chen YS, Ping XL, et al. Cytoplasmic m(6)A reader YTHDF3 promotes mRNA translation[J]. Cell Res, 2017, 27(3): 444-447. DOI: 10.1038/cr.2017.10.
PDF(2250 KB)

Accesses

Citation

Detail

Sections
Recommended

/