Ghosh D, Lalitkumar P G, Wong V J, Hendrickx A G, Sengupta J
Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India and California Regional Primate Research Center, University of California, Davis, CA 95616, USA.
Hum Reprod. 2000 Jan;15(1):180-8. doi: 10.1093/humrep/15.1.180.
The ultrastructural characteristics of peri-implantation stage embryos recovered on day 6 after ovulation from rhesus monkeys with or without mifepristone (RU486) treatment during the early luteal phase were examined in the present study. Monkeys were randomly allocated to two groups; group 1 animals were injected s.c. with 2 ml vehicle (1:4, benzyl benzoate: olive oil, v/v, n = 21) and group 2 animals received a single dose of mifepristone (2 mg/kg body weight, w/v, n = 30) in the same volume of vehicle on day 2 after ovulation in mated cycles. On day 6 after ovulation, female monkeys of both groups were laparotomized and their reproductive tracts were flushed to retrieve preimplantation stage embryos. Embryos that showed frank degeneration or desynchrony on gross microscopical examination were not included in the present study. Preimplantation embryo growth on day 6 after ovulation was significantly (P < 0.05) affected in the morula-blastocyst transition stage in mifepristone-treated monkeys compared with that in the control group of monkeys. Ultrastructurally, administration of mifepristone on day 2 after ovulation depressed preimplantation stage embryo development, characterized by loss of cell polarity, lack of mitochondrial maturity, and lack of differentiation in trophoblast cells. Furthermore, preimplantation embryos from mifepristone-treated animals displayed a higher occurrence of inter-blastomere space, intra-cytoplasmic vacuoles, myelinoid bodies, accumulation of lipid droplets, lysosomes, lipofuscins, autophagosomes and multivesicular bodies. Collectively, it appears that the developmental potential of preimplantation embryos was significantly compromised in mifepristone-treated cycles.
本研究检查了在黄体期早期接受或未接受米非司酮(RU486)治疗的恒河猴排卵后第6天回收的植入前阶段胚胎的超微结构特征。将猴子随机分为两组;第1组动物皮下注射2 ml赋形剂(1:4,苯甲酸苄酯:橄榄油,v/v,n = 21),第2组动物在交配周期排卵后第2天接受相同体积赋形剂中的单剂量米非司酮(2 mg/kg体重,w/v,n = 30)。排卵后第6天,对两组雌性猴子进行剖腹手术,并冲洗其生殖道以回收植入前阶段的胚胎。在大体显微镜检查中显示明显退化或不同步的胚胎不包括在本研究中。与对照组猴子相比,米非司酮处理的猴子在排卵后第6天的植入前胚胎生长在桑椹胚-囊胚过渡阶段受到显著(P < 0.05)影响。在超微结构上,排卵后第2天给予米非司酮会抑制植入前阶段胚胎的发育,其特征是细胞极性丧失、线粒体成熟度缺乏以及滋养层细胞缺乏分化。此外,米非司酮处理动物的植入前胚胎显示出更高的卵裂球间间隙、胞质内空泡、髓样体、脂滴积累、溶酶体、脂褐素、自噬体和多囊泡体发生率。总体而言,在米非司酮处理的周期中,植入前胚胎的发育潜力似乎受到显著损害。