Abstract
Type 1 diabetes (T1D) results in decreased oocyte quality and compromised early embryonic development. Procyanidin B2 (PB2) is a natural compound extracted from grape seeds and has strong antioxidant activity in vivo. This study evaluated the effect of PB2 on oocyte maturation in diabetic mice. Diabetic mice were induced by streptozotocin (STZ) injection. PB2 was supplemented in the in vitro maturation medium, and the ratio of germinal vesicle breakdown (GVBD) and polar body extrusion (PBE), reactive oxygen species (ROS) levels, mitochondrial function, developmental ability, as well as crotonylation at H4K5 were determined in oocytes. PB2 can promote the extrusion of PBE (88.34% vs. 75.02%, P < 0.05); reduce the generation of ROS (1.12 vs. 1.96, P < 0.05); and improve the level of mitochondrial membrane potential (0.87 vs. 0.79 Δφm, P < 0.05), ATP level (1.31 vs. 0.71 pmol, P < 0.05), and mitochondria temperature (618.25 vs. 697.39 pixels, P < 0.05). The addition of PB2 also improved the level of oocyte crotonylation at H4K5 (crH4K5) (47.26 vs. 59.68 pixels, P < 0.05) and increased the blastocyst rate (61.51% vs. 36.07%, P < 0.05) after parthenogenetic activation. Our results are the first to reveal a role for PB2 in promoting the viability of oocytes by regulating the mitochondrial function. Moreover, we uncover that PB2 can improve the level of crH4K5, which provides a new strategy to combat the decline in oocyte quality of diabetic.
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References
Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin N Am. 2010;39(3):481–97. https://doi.org/10.1016/j.ecl.2010.05.011.
Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(11):a007641.
Lee J, Lee HC, Kim SY, Cho GJ, Woodruff TK. Poorly-controlled type 1 diabetes mellitus impairs LH-LHCGR signaling in the ovaries and decreases female fertility in mice. Yonsei Med J. 2019;60(7):667–78.
Gerard-Gonzalez A, Gitelman SE, Cheng P, Dubose SN, Miller KM, Olson BA, et al. Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D exchange clinic registry. J Diabetes. 2013;5(2):216–23.
Greene MF. Spontaneous abortions and major malformations in women with diabetes mellitus. Semin Reprod Endocrinol. 1999;17(2):127–36.
Codner E, Merino PM, Tena-Sempere M. Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update. 2012;18(5):568–85.
May-Panloup P, Boucret L, de la Barca JMC, Desquiret-Dumas V, Ferre-L'Hotellier V, Moriniere C, et al. Ovarian ageing: the role of mitochondria in oocytes and follicles. Hum Reprod Update. 2016;22(6):725–43.
Chiaratti MR, Garcia BM, Carvalho KF, Machado TS, Ribeiro FKD, Macabelli CH. The role of mitochondria in the female germline: implications to fertility and inheritance of mitochondrial diseases. Cell Biol Int. 2018;42(6):711–24.
Chretien D, Benit P, Ha HH, Keipert S, El-Khoury R, Chang YT, et al. Mitochondria are physiologically maintained at close to 50 degrees C. PLoS Biol. 2018;16(1):e2003992.
Ding L, Pan R, Huang X, Wang JX, Shen YT, Xu L, et al. Changes in histone acetylation during oocyte meiotic maturation in the diabetic mouse. Theriogenology. 2012;78(4):784–92.
Tan MJ, Luo H, Lee S, Jin FL, Yang JS, Montellier E, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146(6):1015–27.
Ruiz-Andres O, Dolores Sanchez-Nino M, Cannata-Ortiz P, Ruiz-Ortega M, Egido J, Ortiz A, et al. Histone lysine crotonylation during acute kidney injury in mice. Dis Model Mech. 2016;9(6):633–45. https://doi.org/10.1242/dmm.024455.
Martinez-Moreno JM, Fontecha-Barriuso M, Martin-Sanchez D, Sanchez-Nino MD, Ruiz-Ortega M, Sanz AB, et al. The contribution of histone crotonylation to tissue health and disease: focus on kidney health. Front Pharmacol. 2020;11. https://doi.org/10.3389/fphar.2020.00393.
Tian C, Liu L, Ye X, Fu H, Sheng X, Wang L, et al. Functional oocytes derived from granulosa cells. Cell Rep. 2019;29(13):4256–67.e9. https://doi.org/10.1016/j.celrep.2019.11.080.
Li JR, Jiang YM. Litchi flavonoids: isolation, identification and biological activity. Molecules. 2007;12(4):745–58.
Jung M, Triebel S, Anke T, Richling E, Erkel G. Influence of apple polyphenols on inflammatory gene expression. Mol Nutr Food Res. 2009;53(10):1263–80.
Heidker RM, Caiozzi GC, Ricketts ML. Dietary procyanidins selectively modulate intestinal farnesoid X receptor-regulated gene expression to alter enterohepatic bile acid recirculation: elucidation of a novel mechanism to reduce triglyceridemia. Mol Nutr Food Res. 2016;60(4):727–36.
Yin M, Zhang P, Yu F, Zhang Z, Cai Q, Lu WD, et al. Grape seed procyanidin B2 ameliorates hepatic lipid metabolism disorders in db/db mice. Mol Med Rep. 2017;16(3):2844–50.
Tesch GH, Allen TJ. Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology. 2007;12(3):261–6.
Wang YH, Feng WK, Xue WL, Tan Y, Hein DW, Li XK, et al. Inactivation of GSK-3 beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes. 2009;58(6):1391–402.
Liu XH, Zhang L, Wang P, Li XY, Qiu DH, Li L, et al. Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress in oocytes from diabetic mice. Cell Cycle. 2017;16(13):1302–8.
Xie HY, Xu F, Li Y, Zeng ZB, Zhang R, Xu HJ, et al. Increases in PKC gamma expression in trigeminal spinal nucleus is associated with orofacial thermal hyperalgesia in streptozotocin-induced diabetic mice. J Chem Neuroanat. 2015;63:13–9.
Cheng JM, Li J, Tang JX, Chen SR, Deng SL, Jin C, et al. Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice. Cell Cycle. 2016;15(18):2454–63.
Bao L, Cai XX, Zhang ZF, Li Y. Grape seed procyanidin B2 ameliorates mitochondrial dysfunction and inhibits apoptosis via the AMP-activated protein kinase-silent mating type information regulation 2 homologue 1-PPAR gamma co-activator-1 alpha axis in rat mesangial cells under high-dose glucosamine. Brit J Nutr. 2015;113(1):35–44.
Wang T, Gao Y-Y, Chen L, Nie Z-W, Cheng W, Liu X, et al. Melatonin prevents postovulatory oocyte aging and promotes subsequent embryonic development in the pig. Aging-Us. 2017;9(6):1552–64. https://doi.org/10.18632/aging.101252.
Arai S, Suzuki M, Park SJ, Yoo JS, Wang L, Kang NY, et al. Mitochondria-targeted fluorescent thermometer monitors intracellular temperature gradient. Chem Commun. 2015;51(38):8044–7.
Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med. 1999;27(5–6):612–6.
Liu HG, Liu ZQ, Lu TF, Zhang LY, Cheng JM, Fu XW, et al. Toxic effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal on the maturation and subsequent development of murine oocyte. Ecotoxicol Environ Saf. 2019;181:370–80.
Wang QA, Moley KH. Maternal diabetes and oocyte quality. Mitochondrion. 2010;10(5):403–10.
Li L, Jing Y, Dong M-Z, Fan L-H, Li Q-N, Wang Z-B, et al. Type 1 diabetes affects zona pellucida and genome methylation in oocytes and granulosa cells. Mol Cell Endocrinol. 2020;500:110627. https://doi.org/10.1016/j.mce.2019.110627.
Eppig JJ. Coordination of nuclear and cytoplasmic oocyte maturation in eutherian mammals. Reprod Fertil Dev. 1996;8(4):485–9.
Eppig JJ, Schultz RM, Obrien M, Chesnel F. Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes. Dev Biol. 1994;164(1):1–9. https://doi.org/10.1006/dbio.1994.1175.
Diamond MP, Moley KH, Pellicer A, Vaughn WK, Decherney AH. Effects of streptozotocin-induced and alloxan-induced diabetes-mellitus on mouse follicular and early embryo development. J Reprod Fertil. 1989;86(1):1–10.
Zhang CH, Qian WP, Qi ST, Ge ZJ, Min LJ, Zhu XL, et al. Maternal diabetes causes abnormal dynamic changes of endoplasmic reticulum during mouse oocyte maturation and early embryo development. Reprod Biol Endocrinol. 2013;11:31.
Mao LN, Lou HY, Lou YY, Wang N, Jin F. Behaviour of cytoplasmic organelles and cytoskeleton during oocyte maturation. Reprod BioMed Online. 2014;28(3):284–99.
Quinn P, Wales RG. Relationships between ATP content of preimplantation mouse embryos and their development in-vitro during culture. J Reprod Fertil. 1973;35(2):301–9.
Vanblerkom J, Davis PW, Lee J. ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo-transfer. Hum Reprod. 1995;10(2):415–24.
Hirano T. SMC proteins and chromosome mechanics: from bacteria to humans. Philos Trans R Soc Lond B Biol Soil. 2005;360(1455):507–14.
Duran HE, Simsek-Duran F, Oehninger SC, Jones HW, Castora FJ. The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation. Fertil Steril. 2011;96(2):384–8.
Nagano M, Katagiri S, Takahashi Y. ATP content and maturational/developmental ability of bovine oocytes with various cytoplasmic morphologies. Zygote. 2006;14(4):299–304.
Reers M, Smith TW, Chen LB. J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane-potential. Biochemistry-Us. 1991;30(18):4480–6.
Homma M, Takei Y, Murata A, Inoue T, Takeoka S. A ratiometric fluorescent molecular probe for visualization of mitochondrial temperature in living cells. Chem Commun. 2015;51(28):6194–7.
Gao L, Du M, Zhuan QR, Luo YX, Li JY, Hou YP, et al. Melatonin rescues the aneuploidy in mice vitrified oocytes by regulating mitochondrial heat product. Cryobiology. 2019;89:68–75.
Zhang JW, Xu DQ, Feng XZ. The toxic effects and possible mechanisms of glyphosate on mouse oocytes. Chemosphere. 2019;237:124435.
Cao P, Zhang Y, Huang Z, Sullivan MA, He ZH, Wang JL, et al. The preventative effects of procyanidin on binge ethanol-induced lipid accumulation and ROS overproduction via the promotion of hepatic autophagy. Mol Nutr Food Res. 2019;63(18):e1801255.
Cai XX, Bao L, Ren JW, Li Y, Zhang ZF. Grape seed procyanidin B2 protects podocytes from high glucose-induced mitochondrial dysfunction and apoptosis via the AMPK-SIRT1-PGC-1 alpha axis in vitro. Food Funct. 2016;7(2):805–15.
Ge ZJ, Liang XW, Guo L, Liang QX, Luo SM, Wang YP, et al. Maternal diabetes causes alterations of DNA methylation statuses of some imprinted genes in murine oocytes. Biol Reprod. 2013;88(5):117.
Wan J, Liu H, Chu J, Zhang H. Functions and mechanisms of lysine crotonylation. J Cell Mol Med. 2019;23(11):7163–9. https://doi.org/10.1111/jcmm.14650.
Wei W, Liu XG, Chen JW, Gao SN, Lu L, Zhang HF, et al. Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res. 2017;27(7):898–915.
Wei W, Mao AQ, Tang B, Zeng QF, Gao SN, Liu XG, et al. Large-scale identification of protein crotonylation reveals its role in multiple cellular functions. J Proteome Res. 2017;16(4):1743–52.
Montellier E, Rousseaux S, Zhao YM, Khochbin S. Histone crotonylation specifically marks the haploid male germ cell gene expression program. Bioessays. 2012;34(3):187–93.
Bueno A, Sinzato YK, Sudano MJ, Alvarenga FDLE, Calderon IDP, Rudge MVC, et al. Short and long-term repercussions of the experimental diabetes in embryofetal development. Diabetes Metab Res Rev. 2014;30(7):575–81.
Brown HM, Green ES, Tan TCY, Gonzalez MB, Rumbold AR, Hull ML, et al. Periconception onset diabetes is associated with embryopathy and fetal growth retardation, reproductive tract hyperglycosylation and impaired immune adaptation to pregnancy. Sci Rep. 2018;8(1):2114.
Pampfer S. Peri-implantation embryopathy induced by maternal diabetes. J Reprod Fertil. 2000;55(55):129–39.
Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11(5):797–813.
Acknowledgments
We thank Professor Yong-Tae Chang from POSTECH for giving the MTY. We thank Dr. Keren Cheng for giving the valuable suggestion concerning the manuscript.
Funding
This work was supported by the National Nature Science Foundation Project of China (No. 31101714, 81901562&31372307).
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This research was designed by Xiangwei Fu, Yuxi Luo, and Qingrui Zhuan. The in vitro maturation was performed by Yuxi Luo, the immunofluorescence staining (ROS, MT, H4K5 crotonylation) was performed by Yuxi Luo and Qingrui Zhuan. The cell culture and live imaging were performed by Yuxi Luo and Xingzhu Du. The obtained data were analyzed by Yuxi Luo and Xiangwei Fu. The results were interpreted by Jun Li, Zhengyuan Huang, and Yunpeng Hou. The manuscript was written by Yuxi Luo and Xiangwei Fu.
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This research did not involve human participants. All animal experiments were performed in compliance with the principles and guidelines for the use of laboratory animals and ratified by the Institutional Animal Care and Use Committee of China Agricultural University (AW01040202-1). This ethics statement was also mentioned in the manuscript.
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Luo, Y., Zhuan, Q., Li, J. et al. Procyanidin B2 Improves Oocyte Maturation and Subsequent Development in Type 1 Diabetic Mice by Promoting Mitochondrial Function. Reprod. Sci. 27, 2211–2222 (2020). https://doi.org/10.1007/s43032-020-00241-3
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DOI: https://doi.org/10.1007/s43032-020-00241-3