Does combination of estradiol and sesame oil improve the oocyte quality, embryo development and expressions of Zp3, E-cad, and Ctnnb1 genes in mice? An experimental study
Background: Aging may reduce oocyte maturation, embryo quality, and fertility potential.
Objective: To compare the effect of estradiol (E2) and sesame oil on oocyte and embryo quality between young and old mice.
Materials and Methods: Sixty old and young female mice were divided in to two groups (30 mice/group, grouped by age). Each group was divided into three subgroups of mice treated with sesame oil, E2 + sesame oil, and normal saline as control group. After ovulation induction, some oocytes were considered for in vitro fertilization and the rest were assessed for morphological status. After obtaining the two-cell embryos, the embryos were collected to determine the expression of zona pellucida (ZP) glycoprotein 3, E-cadherin, and β-catenin genes and some of them followed until the blastocysts stage to evaluate the viability.
Results: The findings showed that the mean ZP and perivitelline space thickness increased in the old mice that received the E2 + sesame oil treatment. The number of 2-cell embryos, blastocysts, and live cells were significantly higher in the old group treated with sesame oil respectively (p = 0.018, 0.002, and < 0.0001, respectively). The normal ZP shape and refractile body numbers increased in the old mice that were treated with sesame oil, respectively. The E-cadherin gene was downregulated in the treatment groups compared to the controls.
Conclusion: Sesame oil showed a better response in the old mice, because aging is associated with an increased rate of reactive oxygen species, causing deficiencies in both oocyte and embryo qualities.
Key words: Estradiol, Sesame oil, Gene expression, Oocyte, Mouse.
 Balakier H, Sojecki A, Motamedi G, Bashar S, Mandel R, Librach C. Is the zona pellucida thickness of human embryos influenced by women’s age and hormonal levels? Fertil Steril 2012; 98: 77–83.
 El-Hayek S, Clarke HJ. Follicle-stimulating hormone increases gap junctional communication between somatic and germ-line follicular compartments during murine oogenesis. Biol Reprod 2015; 93: 47.
 Terasaki M, Campagnola P, Rolls MM, Stein PA, Ellenberg J, Hinkle B, et al. A new model for nuclear envelope breakdown. Mol Biol Cell 2001; 12: 503– 510.
 Ge ZJ, Schatten H, Zhang CL, Sun QY. Oocyte ageing and epigenetics. Reproduction 2015; 149: R103–R114.
 Devesa J, Caicedo D. The role of growth hormone on ovarian functioning and ovarian angiogenesis. Front Endocrinol 2019; 10: 450.
 Zarif-Yeganeh M, Rastegarpanah M. Clinical role of silymarin in oxidative stress and infertility: A short review for pharmacy practitioners. J Res Pharm Pract 2019; 8: 181–188.
 Khaneshi F, Nasrolahi O, Azizi SH, Nejati V. Sesame effects on testicular damage in streptozotocininduced diabetes rats. Avicenna J Phytomed 2013; 3: 347–355.
 Ryan E, Galvin K, O’connor TP, Maguire AR, O’Brien NM. Phytosterol, squalene, tocopherol content and fatty acid profile of selected seeds, grains, and legumes. Plant Foods Hum Nutr 2007; 62: 85–91.
 Zhao M, Dean J. The zona pellucida in folliculogenesis, fertilization and early development. Rev Endocr Metab Disord 2002; 3: 19–26.
 Rankin T, Soyal S, Dean J. The mouse zona pellucida: Folliculogenesis, fertility and preimplantation development. Mol Cell Endocrinol 2000; 163: 21–25.
 Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, et al. Molecular cues to implantation. Endocr Rev 2004; 25: 341–373.
 Fleming TP, Sheth B, Fesenko I. Cell adhesion in the preimplantation mammalian embryo and its role in trophectoderm differentiation and blastocyst morphogenesis. Front Biosci 2001; 6: D1000–D1007.
 Nelson WJ. Regulation of cell-cell adhesion by the cadherin-catenin complex. Biochem Soc Trans 2008; 36: 149–155.
 Mohammadzadeh M, Fesahat F, Khoradmehr A, AliKhalili M. Influential effect of age on oocyte morphometry, fertilization rate and embryo development following IVF in mice. Mid Eas Fert Soc J 2018; 23: 117–120.
 Mohammadzadeh M, Mazaheri F, Anbari F, Khalili MA. [The impacts of estrogen and sesame oil on the hippocampal histomorphologic changes in mice]. Shefaye Khatam 2020; 8: 29–38. (in Persian)
 Mohammapour K, Ahmadi M, Kesmati M. The effect of intraperitoneal injection sesame oil on fear conditioning in the female mice. J Anim Biol 2009; 1: 33–39.
 Caligioni CS. Assessing reproductive status/stages in mice. Curr Protoc Neurosci 2009; Appendix: Appendix-4I.
 Butcher RL, Collins W, Fugo NW. Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrous cycle of the rat. Endocrinology 1974; 94: 1704–1708.
 Al-Hasani S, Ozmen B, Koutlaki N, Schoepper B, Diedrich K, Schultze-Mosgau A. Three years of routine vitrification of human zygotes: Is it still fair to advocate slow-rate freezing? Reprod BioMed Online 2007; 14: 288–293.
 Nawroth F, Müller P, Wolf C, Sudik R. Is the zona pellucida thickness of metaphase-II oocytes in an IVF/ICSI program influenced by the patient’s age? Gynecol Obstetric Invest 2001; 52: 55–59.
 Litscher ES, Wassarman PM. The fish egg’s zona pellucida. Curr Top Deve Biol 2018; 130: 275–305.
 Bo G, Bergfelt DR, Brogliatti GM, Pierson RA, Adams GP, Mapletoft RJ. Local versus systemic effects of exogenous estradiol-17β on ovarian follicular dynamics in heifers with progestogen implants. Anim Reprod Sci 2000; 59: 141–157.
 Shi SL, Yao GD, Jin HX, Song WY, Zhang FL, Yang HY, et al. Correlation between morphological abnormalities in the human oocyte zona pellucida, fertilization failure and embryonic development. Int J Clin Exp Med 2016; 9: 260–267.
 Ebner T. Extracytoplasmic markers of human oocyte quality. J Mammal Ova Res 2009; 26: 18–25.
 Combelles CM, Gupta S, Agarwal A. Could oxidative stress influence the in-vitro maturation of oocytes? Reprod Biomed Online 2009; 18: 864–880.
 Luddi A, Capaldo A, Focarelli R, Gori M, Morgante G, Piomboni P, et al. Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF. Reprod Biol Endocrinol 2016; 14: 57.
 Hussain SA, Hameed A, Ajmal I, Nosheen S, Rasul Suleria HA, Song Y. Effects of sesame seed extract as a natural antioxidant on the oxidative stability of sunflower oil. J Food Sci Technol 2018; 55: 4099– 4110.
 Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod 2012; 86: 27.
 Zahmatkesh A, Ansari Mahyari S, Daliri Joupari M, Shirazi A, Rahmani H. Expression of bovine Ecat1 gene in immature and in vitro matured oocytes as well as during early embryonic development. Reprod Domest Anim 2015; 50: 34–40.
 Liu C, Li M, Li T, Zhao H, Huang J, Wang Y, et al. ECAT1 is essential for human oocyte maturation and pre-implantation development of the resulting embryos. Sci Rep 2016; 6: 38192.
 Mahdy AKH, Pavani KC, Baron E, da Silva SM. Studies on gene expression and developmental competence of bovine embryos produced under different conditions of heat stress. In: Abubakar M. Trends and advances in veterinary genetics. Coroitia: Intech Open; 2017: 31–60.
 Jefferson W, Newbold R, Padilla-Banks E, Pepling M. Neonatal genistein treatment alters ovarian differentiation in the mouse: Inhibition of oocyte nest breakdown and increased oocyte survival. Biol Reprod 2006; 74: 161–168.
 Kim H, Hayashi S, Chambon P, Watanabe H, Iguchi T, Sato T. Effects of diethylstilbestrol on ovarian follicle development in neonatal mice. Reprod Toxicol 2009; 27: 55–62.
 Otsuki J, Nagai Y, Chiba K. Lipofuscin bodies in human oocytes as an indicator of oocyte quality. J Assist Reprod Genet 2007; 24: 263–270.