Clock MUTANT MICE HAVING A DIMINISHED CIRCADIAN CLOCK SHOW ABNORMAL IMPLANTATION.
Clock MUTANT MICE HAVING A DIMINISHED CIRCADIAN CLOCK SHOW ABNORMAL IMPLANTATION.
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生物钟缩短的时钟突变小鼠表现出植入异常。
DOI：
10.1071/rdv29n1ab76
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Amano T
中科院分区：
文献类型：
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作者：
Tomoko Amano;Masayuki Anzai;Kazuya Matsumoto;Amano T
生物钟涉及包括时钟在内的昼夜节律基因的协同转录，并调节哺乳动物的昼夜节律，如睡眠和清醒的节奏。在哺乳动物的生殖生理中，存在着发情周期的进展和胚胎发育等时间相关的事件，因此我们检查了Clock Delta-19突变(CL)纯合子小鼠的生殖特征，以阐明昼夜节律时钟对生殖生理的影响。雌性(F)野生型小鼠(WT)和FCL的发情周期相同：FWT和FCL的发情周期由发情、发情和发情/间歇期3个阶段组成，10个FWT和14个FCL的每个阶段和1个发情周期的平均长度相同。因此，我们比较了WT和CL之间4个可能的交配组的结果。14个雄性(M)WT × FWT、10个MCL × FWT、14个MWt × FCL和15个MCL × FCL的交配组合平均产仔数分别为13.4 ± 0.8、12.6 ± 0.4、12.3 ± 0.7和8.6 ± 1.5，并随着母体和胚胎中时钟等位基因突变数的增加而逐渐减少。由于4个交配组的母亲在妊娠期的体重增长没有差异，而且在妊娠中后期没有自然流产的迹象，我们推测一些胚胎在植入之前或在植入时丢失。在着床前即刻(受精后88 h)，交配组间从子宫采集的胚胎数目和达到着床前(囊胚期)的胚胎百分率均无显著差异。而植入后即刻(受精后160 h)，12 MWt × FWT、11 MCL × FWT、13 MWt × FCL和13 MWt × FCL配对的平均着床位点数分别为13.0 ± 1.5、13.1 ± 1.2、11.7 ± 0.8和7.0 ± 1.3，并随着母体和胚胎时钟等位基因突变数的增加而逐渐减少。MWT × FWT、MCL × FWT、MWT × FCL和MCL × FWT子宫下部胚胎平均着床率分别为48.8%、59.3%、69.7%和77.7%。MCL × FWT组与MWT × FWT组之间差异有统计学意义(P <； 0.05)，这种差异可能是由于胚胎基因型的差异，尤其是WT与杂合子胚胎之间的差异。然而，mwt × FCL组植入部位的分布明显少于mCL × Fwt组(P <； 0.0 5)，这可能是由于母系基因的差异，尤其是WT和纯合子突变DAMs之间的差异。这项研究表明，生物钟，可能是母体和胚胎的生物钟，在从受精到分娩的过程中参与了植入。
The circadian clock involves co-operative transcription of circadian genes including Clock and regulates circadian rhythms in mammals such as the rhythm of sleep and wakefulness. In reproductive physiologies in mammals, there are several time-dependent events such as progression of the oestrous cycle and embryonic development, and we therefore checked the reproductive characters of mice homozygous for Clock delta-19 mutation (CL) having a diminished circadian clock to elucidate the effect of the circadian clock on reproductive physiologies. Profiles of the oestrous cycle were the same in female (f) wild-type mice (WT) and fCL: oestrous cycles of both fWT and fCL consisted of the same 3 stages, proestrous, oestrous, and metestrous/diestrous stages, and the average lengths of each stage and one oestrous cycle were the same in 10 fWT and 14 fCL. We therefore compared outcomes from the 4 possible mating groups between WT and CL. Average numbers of newborn pups obtained from mating pairs of 14 male (m) WT × fWT, 10 mCL × fWT, 14 mWT × fCL, and 15 mCL × fCL were 13.4 ± 0.8, 12.6 ± 0.4, 12.3 ± 0.7, and 8.6 ± 1.5, respectively, and gradually decreased depending on the number of mutated Clock alleles in mothers and embryos. Since increases in body weights of the mothers during the gestation period were not different in the 4 mating groups and since there were no signs of spontaneous abortion from mid to late gestation, we reasoned that some embryos were lost before or at the time of implantation. Immediately before implantation (88 h after fertilization), neither the number of embryos collected from uteri nor the percentage of embryos that reached the pre-implantation stage (blastocyst stage) differed significantly among mating groups. In contrast, immediately after implantation (160 h after fertilization), the average numbers of implantation sites in mating pairs of 12 mWT × fWT, 11 mCL × fWT, 13 mWT × fCL, and 13 fCL × fCL were 13.0 ± 1.5, 13.1 ± 1.2, 11.7 ± 0.8, and 7.0 ± 1.3, respectively, and also gradually decreased with increase in the number of mutated Clock alleles in mothers and embryos. This decrease was accompanied by a significant lowering of the positions of implantation sites in uteri, a possible cause of the decrease of the number of newborns and implantation sites, and average percentages of embryos implanted in a lower part of the uterus were 48.8, 59.3, 69.7, and 77.7% in mWT × fWT, mCL × fWT, mWT × fCL, and mCL × fCL, respectively. The difference between the mCL × fWT and mWT × fWT groups was statistically significant (P < 0.05), and this difference was thought to be due to the difference in embryonic genotype, specifically between WT and heterozygous embryos. However, the distribution of implantation sites in the mWT × fCL group was significantly smaller than that in the mCL × fWT group (P < 0.05), presumably due to the difference in maternal genotype, specifically between WT and homozygous mutant dams. This study showed involvement of the circadian clock, possibly the maternal and embryonic circadian clock, in implantation among events that occur from fertilization to parturition.