Loupis A, Ryan J, Waite K, Pollard I
School of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia.
J Matern Fetal Med. 1996 Nov-Dec;5(6):321-7. doi: 10.1002/(SICI)1520-6661(199611/12)5:6<321::AID-MFM6>3.0.CO;2-R.
The present study was designed to investigate whether caffeine administered daily throughout the estrous cycle prior to fertilization affected the development of the subsequent preimplantation day 5 rat embryo. The viability parameters chosen for assessment were glucose utilization, cell number, and stage of embryonic development (morula to hatched blastocyst). Two independently replicated experiments were conducted. Together these experiments demonstrated that after fertilization, a proportion of affected oocytes maturing in a caffeine-perfused ovarian environment used and oxidised glucose at a significantly higher rate and were significantly more advanced developmentally compared with their litter mates or with the control counterparts. Cell number per embryo and the number of embryos recovered (litter size) remained constant, suggesting that caffeine, at the doses used, is unlikely to affect the ovulation rate or prevent fertilization. This study is significant because it demonstrates for the first time that a drug such as caffeine, when administered prior to ovulation and genomic activation, causes a quantitative difference in growth promoting energy utilization in a proportion of susceptible embryos after genome activation. A link between genomic imprinting and changed developmental program in the preimplantation embryos was suggested.
本研究旨在调查在受精前整个发情周期每日给予咖啡因是否会影响随后第5天着床前大鼠胚胎的发育。选择用于评估的活力参数为葡萄糖利用、细胞数量和胚胎发育阶段（桑葚胚至孵化囊胚）。进行了两项独立重复实验。这些实验共同表明，受精后，在咖啡因灌注的卵巢环境中成熟的一部分受影响卵母细胞利用和氧化葡萄糖的速率显著更高，并且与其同窝仔或对照对应物相比，发育明显更成熟。每个胚胎的细胞数量和回收的胚胎数量（窝产仔数）保持不变，这表明所用剂量的咖啡因不太可能影响排卵率或阻止受精。这项研究具有重要意义，因为它首次证明，像咖啡因这样的药物在排卵和基因组激活之前给药时，会在基因组激活后使一部分易感胚胎的促进生长的能量利用产生定量差异。这提示了基因组印记与着床前胚胎发育程序改变之间的联系。
