雌性小鼠不同时期雌激素及其受体表达对Th1/Th2和Th17/Treg免疫平衡的影响

目的 探索雌性小鼠不同时期雌激素及其受体表达对Th1/Th2和Th17/Treg免疫平衡的影响。方法 取2月龄雌性C57BL/6小鼠随机分为发情间期组、发情期组、妊娠期组,取13月龄雌性小鼠作为绝经期组,每组10只。分别检测4组小鼠血清雌激素(E2)水平、脾脏雌激素受体α(ERα)、雌激素受体β(ERβ) mRNA水平以及脾脏单个核细胞Th1、Th2、Th17、Treg亚群比例,计算Th1/Th2、Th17/Treg比值,并分析E2水平、ERαmRNA水平分别与Th1/Th2、Th17/Treg比值的相关性。结果 与发情间期组比,发情期组、妊娠期组小鼠E2水平、ERαmRNA水平、Th2、Treg亚群比例升高(P 0. 05),Th1、Th17亚群比例、Th1/Th2、Th17/Treg比值降低(P 0. 05);绝经期组小鼠E2水平、ERαmRNA水平、Th2、Treg亚群比例降低(P 0. 05),Th1、Th17亚群比例、Th1/Th2、Th17/Treg比值升高(P 0. 05)。E2水平、ERαmRNA水平分别与Th1/Th2、Th17/Treg比值呈负相关(P 0. 05)。结论 雌性小鼠不同时期雌激素及其受体表达水平不同,且与Th1/Th2、Th17/Treg比值呈负相关,可能调节Th1/Th2和Th17/Treg免疫平衡。     

主动免疫治疗对反复自然流产患者外周血Th1/Th2模式表达影响

目的:探讨主动免疫治疗对原因不明性反复自然流产(URSA)患者Th1/Th2模式表达的影响。方法:采用流式细胞仪对30例URSA患者进行主动免疫治疗前后外周血Th1/Th2模式测定,以30例正常已生育妇女作为对照。结果:UR-SA组Th1型细胞因子IFN-γ(18.98±5.37)%,明显高于对照组的(8.69±2.66)%(P<0.05);而Th2型细胞因子IL-4(5.52±0.18)%,明显少于对照组的(6.78±0.61)%(P<0.05),Th1/Th2为3.14,模式向Th1偏移。主动免疫治疗后Th2型细胞因子IL-4水平(10.27±2.04)%及Th1型细胞因子IFN-γ水平(11.73±2.47)%,Th1/Th2为1.41,模式向Th2偏移。结论:URSA患者Th1/Th2模式偏向Th1,主动免疫治疗可使Th1/Th2模式偏向Th2,诱导母胎免疫耐受,使妊娠成功。     

子痫前期患者胎盘组织IL-4 mRNA和IFN-γ mRNA的表达水平

目的:探讨子痫前期的病因及发病机制。方法:用原位杂交法测定子痫前期患者胎盘组织中IFN-γmRNA和IL-4mRNA的基因表达。结果:①IL-4mRNA在正常妊娠组、子痫前期轻度组和子痫前期重度组的表达随病情的加重表达减弱,但3组间两两比较无统计学意义(P>0.05);②IFN-γmRNA的表达随病情的加重表达增强,子痫前期重度组与正常妊娠组、子痫前期轻度组相比差异有统计学意义(P<0.05),且与正常妊娠组相比差异显著(P<0.001);子痫前期轻度组的表达也高于正常妊娠组,但差异无统计学意义(P>0.05);③IFN-γmRNA/IL-4mRNA比值结果显示,随病情的加重比值增大,且子痫前期轻度组、重度组与正常妊娠组两两相比差异均有统计学意义(P<0.05),重度组与正常妊娠组相比差异显著(P<0.001)。结论:子痫前期孕妇胎盘中表现为免疫杀伤的Th1型细胞因子IFN-γmRNA表达增强,表现为免疫保护或免疫营养的Th2型细胞因子IL-4mRNA表达无差异,提示子痫前期患者母胎界面中IFN-γmRNA的高表达与其发病有关,IL-4mRNA在子痫前期的发生、发展中的作用不明显;IFN-γmRNA/IL-4mRNA比值随病情的加重而增大,提示母胎界面的Th1/Th2细胞因子的平衡偏离可能是导致子痫前期发病的病因之一。     

细胞因子与复发性流产的相关性研究进展

<正>常妊娠依赖于母体内细胞因子参与的免疫调控以产生母胎免疫耐受。近年来研究发现复发性流产(recurrent spontaneous abortion,RSA)患者体内存在Th 1/Th 2型细胞因子失衡现象,正常妊娠是以Th 2细胞免疫为主,RSA则以Th 1细胞免疫为主。任何影响Th 1/Th 2细胞比例的因素均可导致流产。随着对细胞因子研究的进展,发现传统Th 1/Th 2细胞模式不能完全解释母胎免疫耐受机制,由此提出了Th 1/Th 2/Th 17及调节性T细胞(regulatory T cell,Treg)模式。研究发现Th 17/Treg比例失衡,影响母体外周血及子宫蜕膜局部细胞因子间的网络平衡,导致流产发生。针对细胞因子的免疫调节治疗(如淋巴细胞免疫治疗、IVIG、TNF-α抑制剂等)可调整T细胞亚群比例及其细胞因子的分泌水平。本文将对Th 1/Th 2/Th 17及Treg模式与RSA的关系进行综述。     

米非司酮终止妊娠与Th1/Th2调节的相关性研究

目的：探讨米非司酮终止妊娠者血清及蜕膜组织液中Th1/Th2型细胞因子的水平及临床意义。方法：采用酶联免疫吸附法检测50例口服米非司酮终止妊娠妇女（药流组）血清及蜕膜组织液中Th1（IL-2、IFN-γ）/Th2（IL-4、IL-10）型细胞因子水平,同时以50例正常健康早孕妇女,要求行人工流产终止妊娠者作为人流组。结果：药流组血清及蜕膜组织中IL-2、IFN-γ的水平明显高于人流组,而IL-4、IL-10含量明显低于人流组,这种变化与药物流产次数无关。结论：米非司酮可以改变流产妇女血清及蜕膜组织液中Th1/Th2平衡,从而终止妊娠。     

砷暴露对小鼠脾脏炎症反应及Th1/Th2的影响

目的探讨慢性饮水砷暴露对小鼠脾脏的炎症反应及Th1/Th2细胞因子和转录因子表达的影响。方法将30只健康SPF级雌性昆明小鼠根据体重按照随机数字表分为对照组和25、50 mg/L NaAsO_2染毒组,每组10只。采用自由饮水方式染毒,染毒6个月后,测定小鼠脾脏组织中炎症因子IL-12和IL-6的mRNA水平。采用Real-time PCR方法分别检测脾脏Th1和Th2的转录因子T-bet、Gata3和细胞因子Ifn-γ、IL-4的mRNA表达水平。同时用Western blot法观察Nrf2、NQO1和GSTO1/2的蛋白表达水平。结果与对照组比较,随着染毒剂量的上升,各染毒组小鼠脾脏炎症因子IL-12和IL-6的mRNA水平均上升,除IL-12的25 mg/L剂量组外,差异均具有统计学意义(P0.05);各染毒组小鼠脾脏细胞因子Ifn-γ和IL-4的转录水平呈上升趋势;Nrf2及其调控的下游蛋白NQO1和GSTO1/2的表达水平明显增加。结论慢性砷暴露小鼠免疫器官脾脏的炎症相关因子IL-12和IL-6明显增加,同时上调Th1和Th2特异性细胞因子的表达水平,调节CD4~+T淋巴细胞亚群的分化,从而发挥对小鼠脾脏的免疫调节效应。     

补肾固冲方治疗原因不明复发性自然流产作用机制的研究

目的:探讨补肾固冲方治疗原因不明复发性流产(URSA)的作用机制。方法:采用病例对照研究方法。URSA患者30例(URSA组),给予补肾固冲方治疗,正常妊娠妇女30例(正常妊娠组)为对照。流式细胞术胞内外双染色法检测两组妇女外周血Th17、Treg亚群分化状态,RT-PCR法检测Th17亚群特异性核转录因子RORγt和Treg亚群特异性核转录因子Foxp3mRNA的转录水平。结果:与正常妊娠组比较,URSA组治疗前外周血Th17亚群比例升高(P=0.008),Treg亚群比例降低(P=0.003),两者比值(Th17/Treg)升高(P=0.001)。与补肾固冲方治疗前比较,治疗后URSA组Th17亚群比例及RORγt mRNA的表达降低(P=0.014,P=0.010);Treg亚群比例及Foxp3mRNA表达升高(P=0.007,P=0.005);Th17/Treg降低(P=0.005);URSA组治疗后与正常妊娠组比较无统计学差异(P=0.759)。相关性分析显示,URSA组治疗后子宫出血天数与Th17亚群比例呈显著正相关(r=0.760,P=0.002),与Treg亚群比例呈负相关(r=-0.540,P=0.009),与Th17/Treg呈正相关(r=0.789,P=0.001)。结论:URSA患者存在Th17/Treg亚群失衡,补肾固冲方通过上调RORγt转录水平、下调Foxp3转录水平,优势诱导Treg亚群分化,逆转Th17/Treg失衡,诱导母胎免疫耐受,进而治疗URSA。     

褐藻胶对小鼠脾淋巴细胞Th1/Th2细胞因子谱影响的体内外研究

目的研究褐藻胶对小鼠脾淋巴细胞Th1/Th2细胞因子谱的影响。方法体内实验:分别设阴性对照组和两个褐藻胶组(0.50g/kgbw和1.50g/kgbw),每组各5只C57BL/6小鼠,分别经口给予纯净水和褐藻胶,30天后分离脾淋巴细胞,培养48h后取上清采用流式微球分析术(CBA)方法分析白细胞介素(IL-2、IL-4、IL-5)、肿瘤坏死因子(TNF)和干扰素-γ(IFN-γ)水平。体外实验:分离C57BL/6种小鼠脾淋巴细胞,与褐藻胶(25mg/ml和50mg/ml)培养48h后取上清采用CBA方法分析IL-2、IL-4、IL-5、TNF和IFN-γ水平。结果体内实验:0.5g/kgbw和1.5g/kgbw褐藻胶组IFN-γ表达水平明显高于阴性对照组(P<0.01),而IL-2和IL-4表达水平下降(P<0.01,P<0.05)。体外实验:25mg/ml和50mg/ml褐藻胶组TNF、IL-2和IL-4表达均明显高于阴性对照组(P<0.05,P<0.01),50mg/ml褐藻胶组IL-5表达水平明显高于阴性对照组(P<0.01)。结论无论是在体内还是体外实验条件下,褐藻胶对小鼠脾淋巴细胞分泌的Th1/Th2细胞因子谱均有影响。     

Th1/Th2失衡与妊娠高血压综合征

妊娠时母胎界面的母体淋巴细胞被激活且可产生各种细胞因子 ,细胞因子在母胎界面局部网络的相对平衡对正常妊娠的维持有重要作用。近年来的研究发现妊娠高血压综合征患者外周血Th1/Th2细胞因子的失衡与其发病有密切关系 ,因此可从妊娠高血压综合征时Th1/Th2失衡的角度考察PIH的发病原因及采取相应的免疫防治措施     

环孢霉素A对不明原因反复自然流产患者外周血Th1/Th2比例转换的研究

目的 探讨环孢霉素A(CsA)对不明原因反复自然流产(URSA)患者外周血Th1/Th2模式的作用.方法 利用CsA作用反复自然流产患者外周血单核细胞( PBMC)的体外实验模型, 以流式细胞仪分析对Th1/Th2 模式的转化.结果 实验组加入CsA培养72 h后可上调IL-4水平,并下调IFN-γ的表达水平.IFN-γ/ IL -4的比值明显低于对照组, 两者差异有统计学意义(P<0.05).CsA 10 μg /mL组与1 μg/mL组IFN/ IL-4的比值, 差异无统计学意义(P>0.05).结论 CsA有利于调控Th1/Th2模式趋向Th2型偏倚,可使URSA患者外周血有利于妊娠维持的Th2型细胞因子(IL-4)表达水平升高,同时降低不利于妊娠维持的Th1型细胞因子(TNF-γ )的表达.从而诱导母胎免疫耐受,使妊娠成功.     

Synergistic effects of DL111-IT combined with mifepristone on termination of early pregnancy in rhesus monkeys

The objectives of this study were to determine the synergistic effects of DL111-IT in combination with mifepristone (RU486) on termination of early pregnancy in rhesus monkeys. Pregnancy was confirmed by tactile sensation of pregnant uterus via anus with finger and ultrasound examination. Pregnancy termination was obtained with vaginal bleeding and abortion materials including fetuses and placentae after treatment. With multiple doses of DL111-IT or RU486 given alone between d24 and d50 of gestation, pregnancy arrests were obtained in 40% (2/5) of monkeys treated with DL111-IT intramuscularly (im) (25 mg x kg(-1) x d(-1) x 3 days), in 20% (1/5) of monkeys treated with 9 mg x kg(-1) x d(-1) x 2 days, and 4.5 mg x kg(-1) on day 3 with RU486 intragastrically (ig). DL111-IT (25 mg x kg(-1) on day 1, im) in combination with RU486 (the same treatment as above) resulted in 100% (10/10) termination of pregnancy and uterine bleeding lasted 6.6 +/- 1.3 days. RU486 (as above treatment) in combination with misoprostal (Miso, 109 microg x kg(-1) on day 3, ig) showed 71.4% (5/7) termination of pregnancy, and uterine bleeding lasted 12.9 +/- 9.6 days. The synergistic effect of DL111-IT plus RU486 enhances termination of early pregnancy and significantly shortens the bleeding time than RU486 plus Miso does in rhesus monkeys.     

Clinical trial on termination of early pregnancy with RU486 in combination with prostaglandin.

Termination of early pregnancy was performed in 1572 healthy women with RU486 (mifepristone, 600mg orally once), followed 36-60 hours later by administration of methyl ester of dl-15-methyl-PGF2 alpha (PG05, 1mg vaginal suppository). Complete abortion was accomplished in 91.2% (1433/1571), incomplete abortion in 4.8% (76/1571), and continued pregnancy in 3.9% (62/1571). The time elapsed between RU486 intake and complete expulsion was 2.4 +/- 1.3 days. Expulsion took place on the third day in 935 women (72%), and on the 4th day in 273 women (21.0%). Uterine bleeding occurred on the second or third day after RU486 intake in 1256 women (88.8%), and lasted 11.7 +/- 6.4 (SD) days, range 2-55 days. One subject had blood transfusion due to excessive bleeding. The main side effects were nausea/vomiting (22.3%), abdominal pain (10.2%), headache/dizziness (4.1%) and diarrhea (2.8%). Fatal side effects have not been reported in this study. About 73% of subjects with complete abortion assessed the treatment as good to excellent. Even in the failed cases, 25-42% of subjects considered the treatment as good. Further studies are needed to determine the optimal dose of the RU486 regimen. It should be emphasized that the treatment must be used under close medical supervision in order to monitor the uterine bleeding.     

Therapeutic abortion in early pregnancy with antiprogestogen RU486 alone or in combination with prostaglandin analogue (gemeprost)

Abortion was attempted in 39 women in early pregnancy (less than 56 days amenorrhea) with the progesterone antagonist RU486 alone (150 mg per day for 4 days) or in combination with a PG analogue, 16,16-dimethyl-trans-delta 2-PGE1 (Gemeprost) in the form of a 1 mg vaginal pessary. Complete abortion was also attempted in 5 women who received RU486 together with 2 X 1 mg PG pessaries. Vaginal bleeding followed by complete abortion occurred in 18 of 19 women who received RU486 + 1 mg PG pessary as compared to only 12 of 20 women who received RU486 alone (P less than 0.01). All women who received RU486 + 2 mg Gemeprost had a complete abortion. The onset of crampy abdominal pain (median: 3 vs 4 days) and vaginal bleeding (3 vs 3 days) was similar in the RU486 and RU486 + PG groups, respectively. Slightly less than half the patients in both groups had nausea and/or vomiting, but the incidence did not differ from that occurring prior to treatment. The mean duration (range) of vaginal bleeding [RU486 alone: 10 (0,29) days and RU486 + PG: (5,34) days], and the measured blood loss [RU486: 53 (2,227) ml and RU486 + PG: 81 (32,222) ml] did not differ significantly between the two treatments. It is concluded that the combination of RU486 and a single PG vaginal pessary is a highly effective means of inducing therapeutic abortion in early pregnancy and offers an alternative to surgery.     

Oral administration of RU 486 and 9-methylene PGE2 for termination of early pregnancy

It has been shown that the antiprogestin RU 486 increases the sensitivity of the early pregnant human uterus to the stimulatory action of prostaglandin E analogues administered vaginally or intramuscularly. To examine if RU 486 also increases uterine sensitivity to a PGE analogue given orally, two investigative approaches were used in the present study: 1) direct registration of uterine contractions before and after administration of 9-methylene PGE₂ in untreated and RU-486-treated early pregnant women; and 2) an efficacy trial involving treatment of pregnant women (amenorrhea of 49 days or less) with 25 mg RU 486 twice daily for three or four days followed by 2.5, 5.0 or 10 mg 9-methylene PGE₂, or 600 mg RU486 followed by 10 mg 9-methylene PGE₂ administered on day 3 and 4. The results showed that oral 9-methylene PGE₂ had a clear stimulatory effect on uterine contractility which was further increased by pretreatment with RU 486. Following 2.5. 5.0 or 10.0 mg 9-methylene PGE₂,the frequency of complete abortion was the same, or approximately 80%. The success rate is higher than that generally reported for RU 486 treatment alone. If 600 mg RU 486 was complemented with 10 mg 9-methylene PGE₂ administered on both days 3 and 4, the frequency of complete abortion increased to 95%. Side effects were of a mild nature and generally occurred following administration of 9-methylene PGE₂. The results of the present study indicate that a combined treatment based on oral administration of both the antiprogestin and the prostaglandin analogue can be developed into a highly effective and simple method to terminate early pregnancy.     

米非司酮药物流产后子宫异常出血与内膜MMP-9、TIMP-1的关系研究

目的：研究米非司酮药物流产后子宫内膜基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶特异性组织抑制物-1（TIMP-1）的表达变化,探讨药物流产后子宫异常出血的机理。方法：取药物流产（简称药流）后和吸宫术后子宫出血〉14天妇女各20例以及药物流产后子宫出血≤14天20例妇女的子宫内膜,应用免疫组化二步法测定子宫内膜MMP-9和TIMP-1的表达,对3组子宫内膜MMP-9和TIMP-1表达进行组织学积分测定。结果：药流非出血组、药流出血组和吸宫出血组子宫内膜组织中MMP-9的表达依次下降（P〈0.05）,TIMP-1表达3组间无差异,3组子宫内膜中MMP-9/TIMP-1组织学积分比值分别为1.47、1.00、1.14。MMP-9/TIMP-1比值药流出血组高于其它两组（P〈0.05）,而药流出血组和吸宫出血组之间子宫内膜MMP-9/TIMP-1比值无差异。结论：子宫内膜MMP-9的下降和MMP-9/TIMP-1比值降低与人工流产术后的子宫出血有关,并非是药物流产后子宫出血所特有的内膜局部因子改变。     

Uses of RU 486: a clinical update

RU 486, a steroid with antiprogesterone and antiglucocorticoid properties, is currently in phase II clinical trials. To date, over 1000 women have been treated with RU 486 for various purposes. In pregnancies of less than 5 weeks' amenorrhea, 600 mg of RU 486 has led to interruption of pregnancy with complete expulsion of the uterine content in approximately 90% of cases, without any need for additional surgical procedures. The success rate declines with increasing duration of pregnancy: complete interruption and expulsion has been recorded in only 58% of pregnancies over 6 weeks' duration. An average of 2.5 days elapses between RU 486 intake and the onset of uterine bleeding. Trials are in progress to determine if the addition of oxytocic agents such as prostaglandins will decrease the rate of incomplete abortion in more advanced pregnancies, reduce the amount of uterine bleeding, and speed up the occurrence of complete abortion. RU 486 has further been noted to result in cervical ripening, and trials are underway to identify optimal conditions for using RU 486 to prepare the cervix for vacuum aspiration or dilatation and curettage. In addition, large scale studies are in progress to assess the preliminary observation that RU 486 leads to complete fetal expulsion within 72 hours in the case of 2nd-trimester fetal death in utero. No major side effects have been associated with RU 486, even when administered in large doses. Finally, data obtained in nonpregnant women indicate that, when given in the mid-luteal phase in large amounts, RU 486 may exert luteolytic effects in addition to its endometrial action. Studies are underway to determine if these findings can be extrapolated to women in whom fertilization has occurred.     

原因不明复发性流产患者蜕膜组织中Th1/Th2比率与B7-1、B7-2的相关性

目的:探讨原因不明复发性流产患者蜕膜组织中Th1/Th2比率与巨噬细胞B7-1、B7-2表达水平的相关性,分析蜕膜组织中共刺激分子B7-1、B7-2及Th1/Th2比率失衡在原因不明复发性流产发病中的作用。方法:用双荧光标记流式细胞技术检测原因不明复发性流产妇女(流产组)和正常妊娠妇女(对照组)的蜕膜组织中Th1/Th2比率和巨噬细胞B7-1、B7-2的表达水平。结果:流产组妇女蜕膜组织中Th1/Th2比率(20.41±3.32)、巨噬细胞B7-1的表达水平(21.57±1.70)%明显高于对照组(P<0.01);流产组妇女蜕膜组织中巨噬细胞B7-2的表达水平(27.82±2.28)%明显低于对照组(P<0.01);流产组妇女蜕膜组织中Th1/Th2比率与蜕膜组织中巨噬细胞B7-1的表达水平之间存在显著正相关(r=0.8663,P<0.01);流产组妇女蜕膜组织中Th1/Th2比率与蜕膜组织中巨噬细胞B7-2的表达水平之间存在显著负相关(r=-0.9016,P<0.01)。结论:原因不明复发性流产患者蜕膜组织中B7-1表达水平增高、B7-2表达水平降低与蜕膜组织中Th1/Th2比率异常有密切的关系,可能是导致原因不明复发性流产发生的重要因素。     

宫清颗粒对人早孕绒毛、蜕膜组织细胞凋亡及信号转导的影响

目的：探讨宫清颗粒对人早孕绒毛、蜕膜组织细胞凋亡及信号转导的影响,为临床防治药物流产后异常子宫出血（简称药流后出血）提供生物学依据。方法：将120例受试者随机分为宫清药流组、茜芷药流组、单纯药流组及负压吸宫组,各30例,收集各组绒毛及蜕膜组织,观察细胞超微结构变化;TUNEL法检测细胞凋亡率（AR）、荧光分光光度计检测细胞内钙离子浓度（[Ca2＋]i）、免疫组化法检测蛋白激酶C（PKC）蛋白表达。结果：宫清药流组绒毛、蜕膜组织细胞超微结构出现典型凋亡改变,AR、[Ca2＋]i升高,PKC蛋白表达降低,与其它3组比较差异有统计学意义（P〈0.05或P〈0.01）。结论：宫清颗粒能影响细胞内Ca2＋及PKC介导的细胞信号转导,诱导人早孕绒毛、蜕膜组织细胞凋亡,促进绒毛与蜕膜组织完全排出,进而防治药物流产后出血。     

新利尿合剂对子痫前期患者Th1/Th2比率的影响

目的:探讨新利尿合剂(多巴胺、酚妥拉明、速尿及硫酸镁)治疗子痫前期的机理。方法:采用流式细胞技术分别测定24例使用新利尿合剂治疗的子痫前期患者(新利尿合剂组)、20例使用硫酸镁治疗的子痫前期患者(硫酸镁组)以及21例正常妊娠妇女(正常妊娠组)Th1、Th2细胞百分比和Th1/Th2比率,同时测量各组受试者血压、肝、肾功能。结果:①新利尿合剂组和硫酸镁组治疗后Th1细胞、Th1/Th2比率均降低(P<0.05),新利尿合剂组较硫酸镁组降低明显(P<0.05),但均未降至正常妊娠状态(P<0.05)。②新利尿合剂组和硫酸镁组治疗后Th2细胞比率无明显变化(P>0.05)。③用药后新利尿合剂组的血压较硫酸镁组有显著下降(P<0.05),肝、肾功能明显好转(P<0.05),但未完全恢复正常妊娠状态(P<0.05)。结论:使用新利尿合剂治疗可以改变Th1细胞与Th1/Th2比率,可以促进子痫前期患者体内Th1/Th2比率趋于平衡,是临床上治疗子痫前期的一种有效、可行的方法。     

Progesterone receptor blockage. Effect on uterine contractility and early pregnancy

RU 486 is an antiprogestin which acts at the receptor level. In the present study the effect of this compound on uterine contractility and sensitivity during early pregnancy was evaluated in 10 patients. Five patients in the 6th to 7th week of pregnancy received 25 mg RU 486 twice daily for four days. On the fourth day of treatment, uterine contractility was recorded. The remaining five early pregnant patients were untreated and served as control. Withdrawal of progesterone locally by RU 486 treatment resulted in the development of a regular uterine activity which was in sharp contrast to the low level contractility pattern found in the untreated control patients. Also the sensitivity to prostaglandin increased following RU 486 treatment. The efficacy of a sequential therapy of RU 486 and the PGE analogue 16-phenoxy-tetranor-PGE2 methyl sulfonylamide for termination of early pregnancy was also studied. Thirty-four early pregnant women (duration of amenorrhea for up to 49 days) admitted to the hospital for termination of their pregnancy volunteered for the study. The patients received 25 mg RU 486 twice or four times daily for four days. In the morning of the fourth day of RU 486 treatment, a small dose (0.25 mg) of the PGE analogue was given as a single intramuscular injection. The combined treatment resulted in complete abortion in 32 patients (94%). One patient experienced an incomplete abortion and in one patient the pregnancy continued unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)