Ezoe Kenji, Yabuuchi Akiko, Tani Tetsuya, Mori Chiemi, Miki Tetsuya, Takayama Yuko, Beyhan Zeki, Kato Yoko, Okuno Takashi, Kobayashi Tamotsu, Kato Keiichi
Kato Ladies Clinic, Shinjuku-ku, Tokyo, Japan.
Laboratory of Animal Reproduction, College of Agriculture, Kinki University, Nara, Japan.
PLoS One. 2015 May 12;10(5):e0126801. doi: 10.1371/journal.pone.0126801. eCollection 2015.
Cryopreservation of mature oocytes and embryos has provided numerous benefits in reproductive medicine. Although successful cryopreservation of germinal-vesicle stage (GV) oocytes holds promise for further advances in reproductive biology and clinical embryology fields, reports regarding cryopreservation of immature oocytes are limited. Oocyte survival and maturation rates have improved since vitrification is being performed at the GV stage, but the subsequent developmental competence of GV oocytes is still low. The purpose of this study was to evaluate the effects of supplementation of the maturation medium with cyclic adenosine monophosphate (cAMP) modulators on the developmental competence of vitrified-warmed GV bovine oocytes. GV oocytes were vitrified-warmed and cultured to allow for oocyte maturation, and then parthenogenetically activated or fertilized in vitro. Our results indicate that addition of a cAMP modulator forskolin (FSK) or 3-isobutyl-1-methylxanthine (IBMX) to the maturation medium significantly improved the developmental competence of vitrified-warmed GV oocytes. We also demonstrated that vitrification of GV oocytes led to a decline in cAMP levels and maturation-promoting factor (MPF) activity in the oocytes during the initial and final phases of maturation, respectively. Nevertheless, the addition of FSK or IBMX to the maturation medium significantly elevated cAMP levels and MPF activity during IVM. Taken together, our results suggest that the cryopreservation-associated meiotic and developmental abnormalities observed in GV oocytes may be ameliorated by an artificial increase in cAMP levels during maturation culture after warming.
成熟卵母细胞和胚胎的冷冻保存为生殖医学带来了诸多益处。尽管生发泡期(GV)卵母细胞的成功冷冻保存有望在生殖生物学和临床胚胎学领域取得进一步进展,但关于未成熟卵母细胞冷冻保存的报道有限。自从在GV期进行玻璃化冷冻以来,卵母细胞的存活率和成熟率有所提高,但GV卵母细胞随后的发育能力仍然较低。本研究的目的是评估在成熟培养基中添加环磷酸腺苷(cAMP)调节剂对玻璃化冷冻-解冻后的GV期牛卵母细胞发育能力的影响。将GV期卵母细胞进行玻璃化冷冻-解冻并培养以使其成熟,然后进行孤雌激活或体外受精。我们的结果表明,在成熟培养基中添加cAMP调节剂福斯高林(FSK)或3-异丁基-1-甲基黄嘌呤(IBMX)可显著提高玻璃化冷冻-解冻后的GV期卵母细胞的发育能力。我们还证明,GV期卵母细胞的玻璃化冷冻分别导致卵母细胞在成熟初始阶段和最终阶段的cAMP水平和促成熟因子(MPF)活性下降。然而,在体外成熟培养期间向成熟培养基中添加FSK或IBMX可显著提高cAMP水平和MPF活性。综上所述,我们的结果表明,在解冻后的成熟培养过程中通过人工提高cAMP水平,可能会改善在GV期卵母细胞中观察到的与冷冻保存相关的减数分裂和发育异常情况。