Immunochemical study of specific "pregnancy protein" during mammalian ontogenesis]

beta1-globulins were found in the rats and guinea pigs in the extracts of placenta during the first term of pregnancy in one third of cases and beginning from the second term in all cases; they were not found in the other organs. These proteins were also present in the blood serum of pregnant rats, guinea pigs, foetuses and in the amniotic fluid, their concentration being much higher than in the placenta.     

Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin,a marinobufagenin antagonist

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats.Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1–20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum.SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups.The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.     

Theophylline neurotoxicity in pregnant rats

The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats.     

Effects of estradiol and progesterone on early embryonic development in aging rats

Regularly cyclic, middle-aged female rats exhibit a decreased incidence of fertility, and those females that are fertile produce small litters. These decreases in fertility and litter size are associated with reduced numbers of normal blastocysts formed and implanted, suggesting that pre- and/or peri-implantation failures may be the causes for these aging-related reproductive declines. The present study examined the relationships and influence of circulating estradiol (E2) and progesterone (P) levels on early embryonic development and implantation in middle-aged rats. Serial blood samples obtained from cannulated, middle-aged pregnant rats revealed minor decreases in plasma P and increases in E2 levels during Days 2-4 of pregnancy, compared to young pregnant rats, resulting in significantly (p less than 0.001) decreased plasma P/E2 ratios. These alterations in endogenous hormone secretion in middle-aged pregnant rats were associated with fewer normal blastocysts on Day 5 of pregnancy and reduced numbers of normally implanting embryos. Correlation analysis further revealed a significant (p less than 0.05) inverse relationship between mean circulating E2 levels and numbers of normal conceptuses on Day 12 of gestation. Moreover, s.c. administration of P implants (in Silastic) to middle-aged pregnant rats increased serum P levels by about 34-40 ng/ml, and significantly (p less than 0.05) reduced the incidence of abnormal embryos before implantation. In contrast, treatment with E2 minipumps produced a sustained rise in serum E2 (by about 7-15 pg/ml) and resulted in the complete absence of embryos in the reproductive tracts by Day 5 of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of blood pressure control on delivery in pregnant rats in a warm environment

The relation between blood pressure and delivery in pregnant rats was investigated when the blood pressure of pregnant rats was controlled by a pressor or antihypertensive drug in the middle or final stage of pregnancy. All of the pregnant rats studied delivered in a 23 degrees C environment in spite of blood pressure control by a pressor or antihypertensive drug. At 33 degrees C, the pregnant rats were divided into two groups whose blood pressure was increased severely (160-175 mm Hg) or moderately (145-155 mm Hg) at 10 days of pregnancy. Those in the former group delivered, but those in the latter died in the final stage of pregnancy. When the pregnant rats in the group with high blood pressure on day 10 were treated with a antihypertensive drug in the middle stage of pregnancy or with a pressor drug in the final stage, the mortality rate was 100 per cent in both cases. The delivery rate was 57 per cent when the pregnant rats were treated with a antihypertensive drug from the middle to the final stage of pregnancy. In the group with low blood pressure on day 10, all of the pregnant rats delivered when they were treated with a pressor drug in the middle stage of pregnancy. However, the delivery rate was 89 per cent when the pregnant rats were treated with antihypertensive drug in the final stage of pregnancy.     

同型半胱氨酸对孕鼠糖代谢的影响与机制分析

目的:探讨同型半胱氨酸(homocysteine,HCY)摄入后对孕鼠糖代谢的影响以及生物学机制分析。方法:孕鼠妊娠10 d后,将实验动物随机分为3组,每组12只,妊娠对照组(Ctrl)腹腔注射生理盐水,同型半胱氨酸高剂量组(HCYH)和同型半胱氨酸低剂量组(HCYL)腹腔注射HCY溶液,注射浓度分别为200 mg/kg·d和100 mg/kg·d,持续20 d(即为HCY20 d)后,利用血糖含量检测试剂盒和胰岛素试剂盒分别检测孕鼠空腹血糖水平、胰岛素水平;葡萄糖检测试剂盒对孕鼠葡萄糖耐量和胰岛素抵抗进行检测;蛋白免疫印迹法检测孕鼠目的蛋白过氧化物酶体增殖物激活受体γ(PPARγ)、葡萄糖转运蛋白4(GLUT4)、蛋白激酶B(AKT)、磷酸化AKT蛋白(P-AKT)的表达。结果:与Ctrl组比较,在孕鼠注射HCY后,空腹血糖水平升高、血清中胰岛素浓度下降、HOMA-β指数下降、HOMA-IR指数升高(P<0.05);摄入葡萄糖后,孕鼠血糖随时间的变化而下降,葡萄糖曲线下面积升高(P<0.05);摄入胰岛素后,孕鼠血糖随时间的变化而升高,胰岛素曲线下面积升高(P<0.05);PPARγ、P-AKT、GLUT4蛋白表达水平下降,HCYH组降低水平更为显著(P<0.05)。结论:孕鼠HCY摄入后,生物体糖代谢紊乱,AKT磷酸化表达水平抑制,HCY可能通过降低PPARγ的表达减少AKT磷酸化,导致胰岛素受体的活化,进而激活了PI3K/AKT通路,减少了脂肪组织中的GLUT4表达,增加了对于葡萄糖的摄取能力。     

High intensity exercise during pregnancy of rats. Effects on mother and offspring

We see in this study the effect of high intensity exercise (90% VO₂ max) in pregnant rats and their offspring depending on the length of pregnancy. The findings were compared with those obtained for sedentary pregnant rats and non-pregnant rats for similar exercise. This allowed for analysing the isolated effects of exercise (against the sedentary non-pregnant rat control group), of pregnancy and of the interaction between the two factors. For checking the effect of the length of pregnancy, each group of rats was subdivided into those with pregnancy terminated or sacrificed on the seventh, fourteenth or twentieth day of the experiment. VO₂ max, post-exertion blood lactic acid level, body weight gain, food intake, feed efficiency, glucose, triglyceride, total cholesterol, total protein and albumin plasmatic concentrations in adult rats, and weight and number of offspring of pregnant rats were determined. Pregnancy increased weight gain and feed efficiency from the first week of the study, accompanied by a greater food intake (from the twelfth day). In the group of pregnant rats subjected to exercise, there was a reduction in weight gain percentage and feed efficiency in the first and third weeks, staying the same in the second week. A greater food intake during the period accompanied this recovery in the second week. In the group of non-pregnant rats subjected to exercise, food intake did not vary. As the weight gain percentage was less in relation to the non-pregnant control group, feed efficiency decreased. Pregnancy induced a drop in blood sugar level starting in the second week, and the exercise performed during pregnancy did not change this behavior. Pregnancy produced, however, an increase in plasmatic concentration of triglycerides and total cholesterol during the third week of pregnancy. Exercise performed by pregnant rats also did not change this behavior, but the increase observed in the third week was less. Exercise performed by non-pregnant rats did not change the blood sugar level and plasmatic concentration of triglycerides and total cholesterol during the entire experiment. Plasmatic concentration of total proteins and albumin showed a drop in the third week of pregnancy, probably due to high fetal use of proteins in this stage. Exercise performed by the pregnant group caused a lower protein drop in the third week, and in the non-pregnant group, determined an increase in plasmatic protein concentrations. The weight of the offspring of mother rats exercised until the end of the second and third weeks of pregnancy was found to be reduced in relation to the sedentary pregnant group. The group exercised until the third week showed a reduction in the number of offspring, indicating a possible fetal reabsorption. These findings confirmed that high intensity exercise can produce deleterious effects on the mother and fetus, especially when applied up to the last stage of pregnancy.     

低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响

目的:研究低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响.方法:将90只孕期大鼠以随机数表法分成正常孕组、子痫前期组、治疗组,每组30只.其中子痫前期组和治疗组大鼠于妊娠第13 d开始皮下注射左旋硝基精氨酸甲酯,建立子痫前期大鼠模型,注射剂量为200mg/(kg·d),正常孕组予以等...     

Immunochemical study of the specific antigens of human amniotic fluid]

Four specific antigens (trophoblastic beta 1-globulin, placental lactogen, alpha 1- and alpha 2-globulins of human placenta) were identified using antisera to the native amniotic fluid. Five antigens with the mobility of prealbumins, alpha 1-globulins, alpha 2-globulins and beta 2-globulins which bear no resemblance with the previously studied antigens were identified using antisera to the acid fraction of the amniotic fluid. Both the prealbumins and alpha 2-globulin were found in the blood serum of foetuses of different age and of newborn infants; these proteins were absent from the blood serum of pregnant women and donors. They received the names of embryonic prealbumine 1, embryonic prealbumine 2 and embryonic alpha 2-globulin. The protein with the mobility of alpha 1-globulins was found in the amniotic fluid of foetuses and in the blood serum of pregnant women only and received the name of amniotic alpha 1-globulin. The concentration of the antigens in question was studied in the developing foetuses and in the blood serum of pregnant women at different stages of pregnancy.     

Autoimmune processes after long-term low-level exposure to electromagnetic fields (experimental results) part 5. Study of the influence of blood serum from rats exposed to low-level electromagnetic fields on pregnancy and fetal and offspring development

The work evaluates the possible adverse effects on pregnancy and fetal and offspring development arising from the injection of blood serum from rats exposed to microwaves at a power density of 500 μW/cm² into intact female rats. The study is performed on 59 pregnant Wistar rats. Intrauterine mortality, embryo and fetal body weights, and placenta weight are used for the evaluation of embryo and fetal development. Generally accepted integral and specific parameters are used for the evaluation of the postnatal development of offspring during the first 30 days of life. It is shown that injection of blood serum from rats subjected to long-term RF exposure at 500 μW/cm² into intact rats on the tenth day of pregnancy results in adverse effects on fetal and offspring development. Higher total in utero and postnatal mortality, as well as delayed offspring development, are recorded.     

Amelioration of some metabolic effects produced by hyperthyroidism in late pregnant rats and their fetuses. Effects on lipids and proteins.

We have studied the effect of 40-45 days administration of 1 mg/kg thyroxine on protein and lipid metabolism in liver, heart, lungs, kidneys and adrenal glands of virgin and 21-day pregnant rats and their fetuses and placentae. The chronic administration of thyroid hormone produced significant increases in serum T3 and T4 in both groups as well as in organ weights and protein concentrations in virgin rats, but much smaller modifications in pregnant ones. Hyperthyroidism decreased the weight of fetal livers and increased that of placentae; protein content was increased in all fetal organs. Hyperthyroidism induced increases in phospholipid concentrations in all the organs and in total lipids only in liver and heart of adult rats, which were not counteracted by pregnancy. Pregnant rats had increases in total lipids in liver and kidneys and in adrenal phospholipids. In hyperthyroid fetuses there was an increase in hepatic total lipids and no changes in phospholipids. Hepatic lipogenesis (measured by in vivo incorporation of 3H2O into lipids) was increased by hyperthyroidism in virgin and pregnant rats, but the increase was significantly smaller in the pregnant hyperthyroid rats compared with the virgin ones. Fetal lipogenesis in liver and lung was not changed. In addition, an increase was observed in lipogenic enzyme (fatty acid synthetase and glucose-6-phosphate dehydrogenase) activities in hyperthyroid virgin rats which was prevented by pregnancy. In fetuses only pulmonary glucose-6-phosphate dehydrogenase was increased when expressed in terms of tissue weight. Our results indicate that the metabolic effect of hyperthyroidism is attenuated in pregnant rats and their fetuses, when compared with adult virgin rats, in most of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of conceptus number to the action of luteinizing hormone-antiserum in the pregnant rat

Treatment of pregnant rats on Day 12 of pregnancy with luteinizing hormone-antiserum (LH-AS) (equine anti-bovine LH) had no effect on the maintenance of pregnancy or serum progesterone levels in rats bearing either 2 or more than 8 conceptuses. In rats with only 1 conceptus, LH-AS administration resulted in a significant decline in serum progesterone to basal levels within 24 h and all animals (n = 6) failed to maintain pregnancy. All rats with either 1, 2 or greater than 8 implantations showed no effect of normal horse serum (NHS) administration. There was no effect of LH-AS administration on serum testosterone levels, compared to NHS-treated controls.     

Role of the nongravid part of the uterus in the luteolytic effects of estrogen in pregnant rats

Effects of a low dose of estradiol on the luteal function were studied in intact pregnant rats. The pregnant rats received daily sc injections of 0.1 microgram estradiol or sesame oil from day 7 to 14 of pregnancy (day 1 = day of insemination). Serum progesterone levels on day 15 were significantly lower in the estrogen-treated group than in the oil-treated group. In order to study how estrogen induced luteolysis, the pregnant rats received each of the following treatments on day 7 of pregnancy: (1) The uterus except that containing a single conceptus was removed by hysterectomy (hysterectomy group); (2) All but a single conceptus were removed by aspiration, so that rats carried only a single conceptus with the whole part of the nongravid uterus (aspiration group). Each group of rats received also sc injections of 0.1 microgram estradiol or sesame oil from day 7 to 14 of pregnancy. Estradiol treatment caused a significant decline in serum progesterone levels in the aspiration group on day 15, but this was not the case in the hysterectomy group. There was no significant difference in serum LH levels among any of the groups on day 15 of pregnancy. These results indicated that estradiol induced luteolysis in the intact pregnant rats, which would, at least in part, be mediated through the uterus.     

Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy

The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3, and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in control and 20- to 21-day pregnant rats. Western analysis showed that expression of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not change. Expression of Mrp2 protein determined by Western analysis of total liver homogenate decreased to 50% of control levels in pregnant rats, consistent with studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments. In isolated perfused liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly decreased in pregnancy, consistent with decreased expression of Mrp2. The expression of the basolateral transporter Mrp1 was not altered in pregnancy, whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression is not necessarily accompanied by increased Mrp3 expression.     

Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na(+)-K(+)-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-alpha)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na(+)-K(+)-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF(2alpha), and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.     

Regulation of insulin release from isolated islets of Langerhans of the rat in pregnancy. The role of adenosine 3':5'-cyclic monophosphate

1. The concentrations of cyclic AMP were compared in islets of Langerhans isolated from the pancreases of normal female and pregnant rats and were higher in islets in pregnancy. 2. There was also a significant increase in adenylate cyclase activity in homogenates of islets from pregnant rats compared with those from normal rats. 3. Increased cyclic AMP concentration in islets from pregnant rats was reflected in increased protein kinase activity. When the cyclic AMP-dependent protein kinase activity was increased by 3-isobutyl-1-methylxanthine this stimulated activity was significantly greater in pregnancy. 4. Insulin-secretion studies with islets from normal and pregnant rats showed that theophylline or 3-isobutyl-1-methylxanthine, which raise intracellular cyclic AMP concentrations, caused a significantly greater insulin secretion in pregnancy. 5. It was also found that in the presence of a glucose concentration too low to stimulate insulin secretion, the latter could be induced if the cyclic AMP concentrations were raised sufficiently with 3-isobutyl-1-methylxanthine. 6. It is suggested that the higher cyclic AMP concentrations observed in islets in pregnancy mediate the greater insulin-secretory capacity, as well as the greater sensitivity of these islets to low glucose concentrations.     

Transplacental transport of alpha 2-macroglobulin (alpha 2M) and induction of alpha 2M in maternal and neonatal rats with acute inflammation.

The aims of this study were to investigate transplacental transport of alpha 2-macroglobulin (alpha 2M) in rats in rats and to examine the degree of alpha 2M induction in maternal and neonatal rats with acute inflammation. Serum was collected from healthy pregnant CD (IGS) rats, neonates of the pregnant rats and their cord blood. Additional serum samples were obtained from pregnant rats inoculated with an inflammatory agent, turpentine oil, their neonates and cord blood, and neonates inoculated with turpentine oil. The serum levels of alpha 2M were measured by means of an enzyme-linked immunosorbent assay. The average serum levels of alpha 2M in healthy neonates and cord blood were about 380 micrograms/ml. Serum a2M level in neonates inoculated with turpentine oil averaged about 580 micrograms/ml. Serum alpha 2M levels in maternal rats inoculated with turpentine oil, neonates from those rats and their cord blood were elevated, the values being 2,000 micrograms/ml or higher. It was demonstrated that induction of alpha 2M in neonatal rats was lower than in maternal rats when inoculated with turpentine oil. These results suggest that alpha 2M is transplacentally transported from maternal rats to fetal ones.     

Plasma protein and blood volume restitution after hemorrhage in conscious pregnant and ovarian steroid-replaced rats

We have previously shown that both plasma protein restitution and plasma volume restitution are significantly enhanced in female rats hemorrhaged during the proestrus phase of the estrous cycle. Estradiol and progesterone levels are markedly elevated during proestrus and also increase during pregnancy. The present studies were therefore designed to determine whether the ability to restore plasma protein and blood volume after hemorrhage is augmented during pregnancy and by chronically elevated estradiol levels. The response to moderate hemorrhage (22-23% blood loss) was evaluated in conscious pregnant rats during early and midgestation and compared with that of virgin female rats studied during metestrus. At 22 h posthemorrhage, plasma volume had increased to greater than basal levels, and blood volume was restored to 93 +/- 1% (metestrus), 91 +/- 2% (early pregnancy), and 98 +/- 2% (midgestation) of control (P > 0.05). Animals hemorrhaged during metestrus or early pregnancy restored the same amount of protein to the plasma as had been removed, whereas those hemorrhaged during midgestation restored nearly 50% more plasma protein than had been removed (P < 0.01). In ovariectomized animals with chronic steroid replacement that maintained plasma progesterone at metestrus levels (15 +/- 2 ng/ml) but raised plasma estradiol to twofold that of midgestation (22 +/- 3 pg/ml), the blood volume and plasma protein restitution responses to hemorrhage did not differ from those of ovariectomized animals with no steroid replacement. In summary, posthemorrhage restoration of plasma protein content is significantly augmented during midgestation, but not during early pregnancy. This augmented response cannot be attributed to chronic elevation of plasma estradiol levels alone.     

Gonadotropin-releasing hormone alters the T helper cytokine balance in the pregnant rat

The interactions between immune-endocrine and reproductive systems are heightened during pregnancy as an adaptive mechanism, and are regulated by a complex array of hormones and cytokines that control the survival of a semiallogeneic conceptus. GnRH can exert direct effects on the immune system via its receptor (GnRH-R) on lymphoid cells. In the present study, we employed in vitro, ex vivo, and in vivo approaches to investigate the role of GnRH in the modulation of T helper cytokines in pregnant rats undergoing termination of pregnancy. Day 8 pregnant rats were infused with a GnRH agonist (GnRH-Ag) for 24 h using an osmotic minipump. Sham control rats were infused with the vehicle, saline. Lymphocytes were isolated from sham and treated rats and polyclonally stimulated with immobilized anti-CD3 antibody. The levels of the signature T helper 1 (Th-1) cytokines (interferon-gamma [IFN-gamma] and interleukin-2 [IL-2]) and Th-2 cytokines (IL-4 and IL-10) were measured in culture supernatants. Using immunoflourescence confocal microscopy, we demonstrated for the first time the spatial localization of GnRH-R protein on the surface of lymphocytes. We observed a marked increase in IFN-gamma and inhibition of IL-4 production from lymphocytes of pregnant rats treated in vitro with different doses of GnRH-Ag. Further, the responsiveness of lymphocytes to produce IFN-gamma was markedly increased in cells cultured ex vivo from GnRH-Ag infused rats, whereas the capacity of lymphocytes to produce IL-4 was significantly inhibited. In addition, GnRH-Ag infusion in pregnant rats induced a shift toward Th-1 cytokines in the serum. We did not observe any significant difference in IL-2 and IL-10 production in response to GnRH-Ag. Our results suggest an additional function for GnRH as a Th-1 inducer and Th-2 inhibitor. GnRH can thus skew the cytokine balance to predominantly Th-1 type in pregnancy, leading to the termination of pregnancy in rats.     

Effect of RU 486 on luteal function in the early pregnant rat

A dose of 30 mg RU 486/kg, an antiprogesterone, was administered to pregnant rats on Day 2 (Group 1) or Day 4 (Group 2) of pregnancy. RU 486 significantly changed serum progesterone and oestradiol concentrations and luteal 3 beta-HSD and 20 alpha-HSD activities in Group 1, and implantation was significantly inhibited. The luteal 3 beta-HSD activity in Group 2 rats on Day 6 was significantly (P less than 0.01) lower than the control value (7.5 +/- 0.6 and 10.1 +/- 0.6 mU/mg protein respectively). This decline in the 3 beta-HSD activity was followed by a marked decrease in the serum progesterone concentration, resulting in a significant decrease of the progesterone/oestradiol ratio and implantation was completely inhibited. The 20 alpha-HSD activity, which could not be detected on Day 6 in the control rats, was twice as great in Group 2 than in Group 1 rats (17.5 +/- 1.2 and 7.4 +/- 3.1 mU/mg protein respectively). Ultrastructural examination of corpora lutea of Group 2 rats confirmed luteolysis. These results suggest that RU 486 has a luteolytic effect and its anti-implantation effect is concomitant with luteolysis of the corpora lutea of pregnancy.