Research Centre for Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, Australia.
Hum Reprod. 2010 Dec;25(12):2999-3011. doi: 10.1093/humrep/deq246. Epub 2010 Sep 24.
Oocyte in vitro maturation (IVM) reduces the need for gonadotrophin-induced ovarian hyperstimulation and its associated health risks but the unacceptably low conception/pregnancy rates have limited its clinical uptake. We report the development of a novel in vitro simulated physiological oocyte maturation (SPOM) system.
Bovine or mouse cumulus-oocyte complexes (COCs) were treated with cAMP modulators for the first 1-2 h in vitro (pre-IVM), increasing COC cAMP levels ∼100-fold. To maintain oocyte cAMP levels and prevent precocious oocyte maturation, COCs were treated during IVM with an oocyte-specific phosphodiesterase inhibitor and simultaneously induced to mature with FSH. Using SPOM, the pre-IVM and IVM treatments synergized to increase bovine COC gap-junctional communication and slow meiotic progression (both P < 0.05 versus control), extending the normal IVM interval by 6 h in bovine and 4 h in mouse. FSH was required to complete maturation and this required epidermal growth factor signalling. These effects on COC had profound consequences for oocyte developmental potential. In serum-free conditions, SPOM increased bovine blastocyst yield (69 versus 27%) and improved blastocyst quality (184 versus 132 blastomeres; both P < 0.05 versus standard IVM). In mice, SPOM increased (all P < 0.05) blastocyst rate (86 versus 55%; SPOM versus control), implantation rate (53 versus 28%), fetal yield (26 versus 8%) and fetal weight (0.9 versus 0.5 g) to levels matching those of in vivo matured oocytes (conventional IVF).
SPOM is a new approach to IVM, mimicing some characteristics of oocyte maturation in vivo and substantially improving oocyte developmental outcomes. Adaption of SPOM for clinical application should have significant implications for infertility management and bring important benefits to patients.
卵母细胞体外成熟（IVM）减少了对促性腺激素诱导的卵巢过度刺激及其相关健康风险的需求，但不可接受的低妊娠/怀孕率限制了其临床应用。我们报告了一种新的体外模拟生理卵母细胞成熟（SPOM）系统的开发。
牛或小鼠卵丘-卵母细胞复合物（COC）在体外最初的 1-2 小时用 cAMP 调节剂处理（预-IVM），将 COC 的 cAMP 水平提高约 100 倍。为了维持卵母细胞 cAMP 水平并防止过早的卵母细胞成熟，在 IVM 期间用卵母细胞特异性磷酸二酯酶抑制剂处理 COC，并同时用 FSH 诱导其成熟。使用 SPOM，预-IVM 和 IVM 处理协同作用增加了牛 COC 的缝隙连接通讯并减缓了减数分裂进程（均 P <0.05 与对照相比），将牛的正常 IVM 间隔延长了 6 小时，将小鼠的 IVM 间隔延长了 4 小时。FSH 是完成成熟所必需的，这需要表皮生长因子信号。这些 COC 的影响对卵母细胞的发育潜力产生了深远的影响。在无血清条件下，SPOM 增加了牛胚泡的产量（69%比 27%），并改善了胚泡质量（184 个比 132 个卵裂球；均 P <0.05 与标准 IVM 相比）。在小鼠中，SPOM 增加了（均 P <0.05）胚泡率（86%比 55%；SPOM 比对照）、着床率（53%比 28%）、胎儿产量（26%比 8%）和胎儿体重（0.9 克比 0.5 克），达到与体内成熟卵母细胞（常规 IVF）相匹配的水平。
SPOM 是一种新的 IVM 方法，模拟了卵母细胞在体内成熟的一些特征，并显著改善了卵母细胞的发育结果。SPOM 的临床应用适应应该对不孕管理有重要意义，并为患者带来重要益处。
