小鼠体内卵母细胞成熟同步化后体外受精结果的改善。
Improvement in in vitro fertilization outcome following in vivo synchronization of oocyte maturation in mice.
作者信息
Taiyeb Ahmed M, Muhsen-Alanssari Saeeda A, Dees W L, Ridha-Albarzanchi Mundhir T, Kraemer Duane C
机构信息
Baylor College of Medicine, Houston, TX 77030, USA Barz IVF Center for Embryo Research and Infertility Treatment, 40 Koyah Street, Brayate, Erbil, Iraq
Barz IVF Center for Embryo Research and Infertility Treatment, 40 Koyah Street, Brayate, Erbil, Iraq.
出版信息
Exp Biol Med (Maywood). 2015 Apr;240(4):519-26. doi: 10.1177/1535370214549533. Epub 2014 Sep 21.
Synchronization of oocyte maturation in vitro has been shown to produce higher in vitro fertilization (IVF) rates than those observed in oocytes matured in vitro without synchronization. However, the increased IVF rates never exceeded those observed in oocytes matured in vivo without synchronization. This study was therefore designed to define the effect of in vivo synchronization of oocyte maturation on IVF rates. Mice were superovulated and orally treated with 7.5 mg cilostazol (CLZ), a phosphodiesterase 3A (PDE3A) inhibitor, to induce ovulation of immature oocytes at different stages depending on frequency and time of administration of CLZ. Mice treated with CLZ ovulated germinal vesicle (GV) or metaphase I (MI) oocytes that underwent maturation in vitro or in vivo (i.e. in the oviduct) followed by IVF. Superovulated control mice ovulated mature oocytes that underwent IVF directly upon collection. Ovulated MI oocytes matured in vitro or in vivo had similar maturation rates but significantly higher IVF rates, 2-4 cell embryos, than those observed in control oocytes. Ovulated GV oocytes matured in vitro showed similar maturation rates but significantly higher IVF rates than those observed in control oocytes. However, ovulated GV oocytes matured in vivo had significantly lower IVF rates than those noted in control oocytes. It is concluded that CLZ is able to synchronize oocyte maturation and improve IVF rates in superovulated mice. CLZ may be capable of showing similar effects in humans, especially since temporal arrest of human oocyte maturation with other PDE3A inhibitors in vitro was found to improve oocyte competence level. The capability of a clinically approved PDE3A inhibitor to improve oocyte fertilization rates in mice at doses extrapolated from human therapeutic doses suggests the potential scenario of the inclusion of CLZ in superovulation programs. This may improve IVF outcomes in infertile patients.
体外卵母细胞成熟同步化已被证明比未同步化的体外成熟卵母细胞产生更高的体外受精（IVF）率。然而，增加的IVF率从未超过未同步化的体内成熟卵母细胞所观察到的IVF率。因此，本研究旨在确定卵母细胞成熟体内同步化对IVF率的影响。对小鼠进行超排卵，并口服7.5毫克西洛他唑（CLZ），一种磷酸二酯酶3A（PDE3A）抑制剂，根据CLZ给药的频率和时间诱导不同阶段未成熟卵母细胞排卵。用CLZ处理的小鼠排出的生发泡（GV）或中期I（MI）卵母细胞在体外或体内（即在输卵管中）成熟，然后进行IVF。超排卵的对照小鼠排出成熟卵母细胞，收集后直接进行IVF。在体外或体内成熟的排出MI卵母细胞具有相似的成熟率，但IVF率显著更高，即2-4细胞胚胎，高于对照卵母细胞。在体外成熟的排出GV卵母细胞显示出相似的成熟率，但IVF率显著高于对照卵母细胞。然而，在体内成熟的排出GV卵母细胞的IVF率显著低于对照卵母细胞。结论是CLZ能够使超排卵小鼠的卵母细胞成熟同步化并提高IVF率。CLZ可能在人类中表现出类似的效果，特别是因为发现用其他PDE3A抑制剂在体外暂时阻止人类卵母细胞成熟可提高卵母细胞的能力水平。一种临床批准的PDE3A抑制剂在从小鼠治疗剂量推算出的剂量下提高小鼠卵母细胞受精率的能力表明，CLZ有可能被纳入超排卵方案。这可能会改善不孕患者的IVF结果。
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