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Activated PI3K/AKT Signaling Pathway Associates with Oxidative Stress and Impaired Developmental Potential of Vitrified-Thawed Oocytes

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Abstract

It was suggested that the compromised developmental potential of vitrified-thawed oocytes was due to the oxidative stress occurred during the process. PI3K/AKT signaling pathway is important in response to stress. The present study aimed to investigate the role of PI3K/AKT played in oocyte vitrification and thawing. The results revealed that the fertilization rate, cleavage rate, as well as the blastocyst formation rate were significantly lower in the vitrified-thawed oocytes than that of the control counterparts [63.81 ± 7.19 vs. 82.00 ± 4.21% (P < 0.05), 58.89 ± 8.39 vs. 78.92 ± 2.78% (P < 0.05), and 59.37 ± 7.03 vs. 74.56 ± 5.06% (P < 0.05), respectively]. Significantly increased reactive oxygen species (ROS) level (P < 0.01), decreased mitochondrial membrane potential (P < 0.01), and declined SIRT3 expression level (P < 0.01) were observed in vitrified-thawed oocytes compared with that of the fresh group. In addition, enhanced PIK3CA was quantified (P < 0.05), and the protein expression levels of PIK3CA (P < 0.05) and P-AKT (P < 0.01) were increased in vitrified-thawed oocytes compared to the fresh ones. Also, decreased SIRT3 level was observed after vitrification/thawing (P < 0.01). In conclusion, our data demonstrated a link between activated PI3K/AKT signaling pathway in response to oxidative stress and compromised developmental potential in vitrified-thawed oocytes.

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References

  1. Herrero L, Pareja S, Losada C, Cobo AC, Pellicer A, Garcia-Velasco JA. Avoiding the use of human chorionic gonadotropin combined with oocyte vitrification and GnRH agonist triggering versus coasting: a new strategy to avoid ovarian hyperstimulation syndrome. Fertil Steril. 2011;95(3):1137–40.

    CAS  PubMed  Google Scholar 

  2. De Vos M, Smitz J, Woodruff TK. Fertility preservation in women with cancer. Lancet. 2014;384(9950):1302–10.

    PubMed  PubMed Central  Google Scholar 

  3. Chamayou S, Bonaventura G, Alecci C, Tibullo D, di Raimondo F, Guglielmino A, et al. Consequences of metaphase II oocyte cryopreservation on mRNA content. Cryobiology. 2011;62(2):130–4.

    CAS  PubMed  Google Scholar 

  4. Monzo C, Haouzi D, Roman K, Assou S, Dechaud H, Hamamah S. Slow freezing and vitrification differentially modify the gene expression profile of human metaphase II oocytes. Hum Reprod. 2012;27(7):2160–8.

    CAS  PubMed  Google Scholar 

  5. Shirazi A, Naderi MM, Hassanpour H, Heidari M, Borjian S, Sarvari A, et al. The effect of ovine oocyte vitrification on expression of subset of genes involved in epigenetic modifications during oocyte maturation and early embryo development. Theriogenology. 2016;86(9):2136–46.

    CAS  PubMed  Google Scholar 

  6. Cheng KR, Fu XW, Zhang RN, Jia GX, Hou YP, Zhu SE. Effect of oocyte vitrification on deoxyribonucleic acid methylation of H19, Peg3, and Snrpn differentially methylated regions in mouse blastocysts. Fertil Steril. 2014;102(4):1183–90 e1183.

    CAS  PubMed  Google Scholar 

  7. Ghazifard A, Salehi M, Ghaffari Novin M, Bandehpour M, Keshavarzi S, Fallah Omrani V, et al. Anacardic acid reduces acetylation of H4K12 in mouse oocytes during vitrification. Cell J. 2019;20(4):552–8.

    PubMed  Google Scholar 

  8. Goldman KN, Noyes NL, Knopman JM, McCaffrey C, Grifo JA. Oocyte efficiency: does live birth rate differ when analyzing cryopreserved and fresh oocytes on a per-oocyte basis? Fertil Steril. 2013;100(3):712–7.

    PubMed  Google Scholar 

  9. Braga DP, Setti AS, Figueira RC, Azevedo Mde C, Iaconelli A Jr, Lo Turco EG, et al. Freeze-all, oocyte vitrification, or fresh embryo transfer? Lessons from an egg-sharing donation program. Fertil Steril. 2016;106(3):615–22.

    PubMed  Google Scholar 

  10. Amoushahi M, Salehnia M, Mowla SJ. Vitrification of mouse MII oocyte decreases the mitochondrial DNA copy number, TFAM gene expression and mitochondrial enzyme activity. J Reprod Infertil. 2017;18(4):343–51.

    PubMed  PubMed Central  Google Scholar 

  11. Nohales-Corcoles M, Sevillano-Almerich G, Di Emidio G, et al. Impact of vitrification on the mitochondrial activity and redox homeostasis of human oocyte. Hum Reprod. 2016;31(8):1850–8.

    CAS  PubMed  Google Scholar 

  12. Succu S, Gadau SD, Serra E, et al. A recovery time after warming restores mitochondrial function and improves developmental competence of vitrified ovine oocytes. Theriogenology. 2018;110:18–26.

    PubMed  Google Scholar 

  13. Amidi F, Khodabandeh Z, Nori Mogahi MH. Comparison of the effects of Vitrification on gene expression of mature mouse oocytes using Cryotop and open pulled straw. Int J Fertil Steril. 2018;12(1):61–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Tatone C, Di Emidio G, Barbonetti A, et al. Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Hum Reprod Update. 2018;24(3):267–89.

    CAS  PubMed  Google Scholar 

  15. Bagul PK, Katare PB, Bugga P, Dinda AK, Banerjee SK. SIRT-3 modulation by resveratrol improves mitochondrial oxidative phosphorylation in diabetic heart through deacetylation of TFAM. Cells. 2018;7(12).

    CAS  PubMed Central  Google Scholar 

  16. Lee J, Kim Y, Liu T, et al. SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease. Aging Cell. 2018;17(1).

    PubMed Central  Google Scholar 

  17. Wang Y, Zhang ML, Zhao LW, Kuang YP, Xue SG. Enhancement of the efficiency of oocyte vitrification through regulation of histone deacetylase 6 expression. J Assist Reprod Genet. 2018;35(7):1179–85.

    PubMed  PubMed Central  Google Scholar 

  18. Zhang TY, Sun XF, Li L, Ma JM, Zhang RQ, Li N, et al. Ochratoxin A exposure impairs porcine granulosa cell growth via the PI3K/AKT signaling pathway. J Agric Food Chem. 2019;67(9):2679–90.

    CAS  PubMed  Google Scholar 

  19. Artini PG, Tatone C, Sperduti S, et al. Cumulus cells surrounding oocytes with high developmental competence exhibit down-regulation of phosphoinositol 1,3 kinase/protein kinase B (PI3K/AKT) signalling genes involved in proliferation and survival. Hum Reprod. 2017;32(12):2474–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Andrade GM, da Silveira JC, Perrini C, del Collado M, Gebremedhn S, Tesfaye D, et al. The role of the PI3K-Akt signaling pathway in the developmental competence of bovine oocytes. PLoS One. 2017;12(9):e0185045.

    PubMed  PubMed Central  Google Scholar 

  21. Jeong PS, Yoon SB, Choi SA, et al. Iloprost supports early development of in vitro-produced porcine embryos through activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. Reprod Fertil Dev. 2017;29(7):1306–18.

    CAS  PubMed  Google Scholar 

  22. Gao L, Jia G, Li A, Ma H, Huang Z, Zhu S, et al. RNA-Seq transcriptome profiling of mouse oocytes after in vitro maturation and/or vitrification. Sci Rep. 2017;7(1):13245.

    PubMed  PubMed Central  Google Scholar 

  23. Yoon SY, Eum JH, Cha SK, Yoon TK, Lee DR, Lee WS. Prematuration culture with phosphodiesterase inhibitors after vitrification may induce recovery of mitochondrial activity in vitrified mouse immature oocytes. Biopreserv Biobank. 2018;16(4):296–303.

    CAS  PubMed  Google Scholar 

  24. Cao Z, Zhang M, Xu T, Chen Z, Tong X, Zhang D, et al. Vitrification of murine mature metaphase II oocytes perturbs DNA methylation reprogramming during preimplantation embryo development. Cryobiology. 2019;87:91–8.

    CAS  PubMed  Google Scholar 

  25. Pan B, Yang H, Wu Z, et al. Melatonin improves parthenogenetic development of vitrified(−)warmed mouse oocytes potentially by promoting G1/S cell cycle progression. Int J Mol Sci. 2018;19(12).

    PubMed Central  Google Scholar 

  26. Matilla E, Martin-Cano FE, Gonzalez-Fernandez L, Sanchez-Margallo FM, Alvarez IS, Macias-Garcia B. N-acetylcysteine addition after vitrification improves oocyte mitochondrial polarization status and the quality of embryos derived from vitrified murine oocytes. BMC Vet Res. 2019;15(1):31.

    PubMed  PubMed Central  Google Scholar 

  27. Lei T, Guo N, Liu JQ, Tan MH, Li YF. Vitrification of in vitro matured oocytes: effects on meiotic spindle configuration and mitochondrial function. Int J Clin Exp Pathol. 2014;7(3):1159–65.

    PubMed  PubMed Central  Google Scholar 

  28. Lei T, Guo N, Tan MH, Li YF. Effect of mouse oocyte vitrification on mitochondrial membrane potential and distribution. J Huazhong Univ Sci Technolog Med Sci. 2014;34(1):99–102.

    CAS  PubMed  Google Scholar 

  29. Dai J, Wu C, Muneri CW, et al. Changes in mitochondrial function in porcine vitrified MII-stage oocytes and their impacts on apoptosis and developmental ability. Cryobiology. 2015;71(2):291–8.

    CAS  PubMed  Google Scholar 

  30. Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11(5):797–813.

    PubMed  Google Scholar 

  31. Lord T, Aitken RJ. Oxidative stress and ageing of the post-ovulatory oocyte. Reproduction. 2013;146(6):R217–27.

    CAS  PubMed  Google Scholar 

  32. Wang Y, Zhang M, Chen ZJ, Du Y. Resveratrol promotes the embryonic development of vitrified mouse oocytes after in vitro fertilization. In Vitro Cell Dev Biol Anim. 2018;54(6):430–8.

    CAS  PubMed  Google Scholar 

  33. Trapphoff T, Heiligentag M, Simon J, Staubach N, Seidel T, Otte K, et al. Improved cryotolerance and developmental potential of in vitro and in vivo matured mouse oocytes by supplementing with a glutathione donor prior to vitrification. Mol Hum Reprod. 2016;22(12):867–81.

    CAS  PubMed  Google Scholar 

  34. Li Z, Gu R, Lu X, Zhao S, Feng Y, Sun Y. Preincubation with glutathione ethyl ester improves the developmental competence of vitrified mouse oocytes. J Assist Reprod Genet. 2018;35(7):1169–78.

    PubMed  PubMed Central  Google Scholar 

  35. Moawad AR, Xu B, Tan SL, Taketo T. L-carnitine supplementation during vitrification of mouse germinal vesicle stage-oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. Hum Reprod. 2014;29(10):2256–68.

    CAS  PubMed  Google Scholar 

  36. Spricigo JF, Morato R, Arcarons N, et al. Assessment of the effect of adding L-carnitine and/or resveratrol to maturation medium before vitrification on in vitro-matured calf oocytes. Theriogenology. 2017;89:47–57.

    CAS  PubMed  Google Scholar 

  37. Lombard DB, Zwaans BM. SIRT3: as simple as it seems? Gerontology. 2014;60(1):56–64.

    CAS  PubMed  Google Scholar 

  38. Kawamura Y, Uchijima Y, Horike N, Tonami K, Nishiyama K, Amano T, et al. Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest. J Clin Invest. 2010;120(8):2817–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhao HC, Ding T, Ren Y, Li TJ, Li R, Fan Y, et al. Role of Sirt3 in mitochondrial biogenesis and developmental competence of human in vitro matured oocytes. Hum Reprod. 2016;31(3):607–22.

    CAS  PubMed  Google Scholar 

  40. Liu X, Zhang L, Wang P, Li X, Qiu D, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Shi H, Deng HX, Gius D, Schumacker PT, Surmeier DJ, Ma YC. Sirt3 protects dopaminergic neurons from mitochondrial oxidative stress. Hum Mol Genet. 2017;26(10):1915–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Li Y, He L, Zeng N, Sahu D, Cadenas E, Shearn C, et al. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling regulates mitochondrial biogenesis and respiration via estrogen-related receptor alpha (ERRalpha). J Biol Chem. 2013;288(35):25007–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Noh EM, Park J, Song HR, et al. Skin aging-dependent activation of the PI3K signaling pathway via downregulation of PTEN increases intracellular ROS in human dermal fibroblasts. Oxidative Med Cell Longev. 2016;2016:6354261.

    Google Scholar 

  44. Goo CK, Lim HY, Ho QS, Too HP, Clement MV, Wong KP. PTEN/Akt signaling controls mitochondrial respiratory capacity through 4E-BP1. PLoS One. 2012;7(9):e45806.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Cao H, Yu D, Yan X, et al. Hypoxia destroys the microstructure of microtubules and causes dysfunction of endothelial cells via the PI3K/stathmin1 pathway. Cell Biosci. 2019;9:20.

    PubMed  PubMed Central  Google Scholar 

  46. Park H, Lim W, You S, Song G. Oxibendazole induces apoptotic cell death in proliferating porcine trophectoderm and uterine luminal epithelial cells via mitochondria-mediated calcium disruption and breakdown of mitochondrial membrane potential. Comp Biochem Physiol C Toxicol Pharmacol. 2019;220:9–19.

    CAS  PubMed  Google Scholar 

  47. Aroui S, Dardevet L, Najlaoui F, et al. PTEN-regulated AKT/FoxO3a/Bim signaling contributes to human cell glioblastoma apoptosis by platinum-maurocalcin conjugate. Int J Biochem Cell Biol. 2016;77(Pt A):15–22.

    CAS  PubMed  Google Scholar 

  48. Wang LF, Huang CC, Xiao YF, Guan XH, Wang XN, Cao Q, et al. CD38 deficiency protects heart from high fat diet-induced oxidative stress via activating Sirt3/FOXO3 pathway. Cell Physiol Biochem. 2018;48(6):2350–63.

    CAS  PubMed  Google Scholar 

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Funding

This work was supported by Natural Science Foundation of Hebei Province (No. H2015206453).

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  1. Department of Reproductive Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, People’s Republic of China

    Jun Li, Xuemei Yang, Fang Liu, Yaman Song & Yuanke Liu

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Jun Li contributed to conceive and design, data acquisition, analysis, drafting, and revision of the article. Xuemei Yang and Yaman Song contributed to sample collection, determination, and statistical analysis. Fang Liu participated in the design of the study. Yuanke Liu participated in sample collection and data analysis. All authors read and approved the final manuscript.

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Li, J., Yang, X., Liu, F. et al. Activated PI3K/AKT Signaling Pathway Associates with Oxidative Stress and Impaired Developmental Potential of Vitrified-Thawed Oocytes. Reprod. Sci. 27, 404–410 (2020). https://doi.org/10.1007/s43032-019-00036-1

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