dinoprost and Fetal-Resorption

This study in cats compared the effects of a natural prostaglandin F2 alpha (PGF2 alpha) and cabergoline, administered on and after day 30 after mating, with regard to the plasma progesterone concentration, the induction of abortion and the side effects of each regimen. PGF2 alpha, through a direct luteolytic action, induced abortion by an abrupt and rapid (24 h) decline in the plasma progesterone concentration. Using doses (2 mg per cat) comparable to the ones selected in a previous study, 100% of abortions (4/4) in cats treated from day 33 of gestation were obtained. Cabergoline (1.65 micrograms kg-1 day-1, administered subcutaneously for 5 days), through its antiprolactinic action induced abortion in 80% (4/5) of the cats treated on day 30 of gestation. The abortion was initiated by means of a reduction in plasma progesterone concentration to < 1 ng ml-1. This reduction was not as rapid (3-4 days), however, as that obtained with PGF2 alpha (24 h). Prostaglandins always induced significant side effects such as nausea, prostration, vomiting and diarrhoea, within 10 min following injection, whereas cabergoline never induced side effects or behavioural disturbances. In addition, cabergoline usually induced abortion through fetal resorption (75% of cases), without any clinical sign other than some vaginal discharge.

Topics: Abortifacient Agents; Abortion, Induced; Animals; Cabergoline; Cats; Dinoprost; Drug Evaluation; Ergolines; Female; Fetal Resorption; Pregnancy; Pregnancy, Animal; Progesterone; Prolactin

The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance in diabetic embryopathy is unclear. We therefore investigated the role of RAGE in diabetic embryopathy using streptozotocin induced diabetes in female wild type (WT) C57Bl/6N and RAGE knockout C57Bl/6N (RAGE(-/-)) mice, mated with control males of the same genotype. Maternal diabetes induced more fetal resorption and malformation (facial skeleton, neural tube) in the WT than in the RAGE(-/-) fetuses. Maternal plasma glucose and methylgyoxal concentrations, as well as embryonic N(ε)-carboxymethyl-lysine (CML) levels were increased to the same extent in diabetic WT and RAGE(-/-) pregnancy. However, maternal diabetes induced increased fetal hepatic isoprostane 8-iso-PGF2α levels (oxidative stress marker) and embryonic activation of NFκB in WT only (not in RAGE(-/-) embryos). The association between RAGE knockout and diminished embryonic dysmorphogenesis in diabetic pregnancy suggests that embryonic RAGE activation is involved in diabetic embryopathy.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Dinoprost; Embryo, Mammalian; Embryonic Development; Female; Fetal Development; Fetal Resorption; Gene Expression; Liver; Lysine; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Pregnancy; Pregnancy in Diabetics; Pyruvaldehyde; Receptor for Advanced Glycation End Products

Maternal Type I (insulin-dependent) diabetes mellitus is associated with an increased risk for fetal malformations and spontaneous abortions. Although the pathogenic mechanism is not fully understood, reactive oxygen species have been shown to contribute to the pathogenesis in experimental studies. By measuring 8-iso-PGF2alpha and protein carbonyls, radical oxygen damage to lipids and proteins can be estimated. The aim of this study was to investigate the status of lipid peroxidation and protein carbonylation in mothers and fetuses in experimental diabetic pregnancy.. Non-pregnant and pregnant rats with and without streptozotocin-induced diabetes were studied after 4 weeks of diabetes or at gestational day 19, respectively. Gross morphology of the offspring was studied and 24 h urine, plasma, amniotic fluid, maternal and fetal livers were collected. Concentrations of 8-iso-PGF2alpha, 15-keto-DH-PGF2alpha and other oxidative stress variables were measured.. Malformation and resorption rates were increased in diabetic litters, whereas fetal weights were decreased in the control rats. There were no statistically significant differences in maternal plasma concentrations of 8-iso-PGF2alpha, but plasma protein carbonyl content was increased in the diabetic groups. Pregnancy increased 24 h urinary excretion of 8-iso-PGF2alpha in diabetic rats but not in the control rats. There was no difference in the amniotic fluid concentration of 8-iso-PGF2alpha between the normal and the diabetic group. However, in the diabetic group there was a correlation between the uterine horn concentration of 8-iso-PGF2alpha and the percentage of resorptions.. In diabetic pregnancy, both diabetes and pregnancy are promoting oxygen radical damage. Fetal oxidative stress markers do not clearly reflect fetal morphology.

Topics: Amniotic Fluid; Animals; Congenital Abnormalities; Diabetes Mellitus, Experimental; Dinoprost; F2-Isoprostanes; Female; Fetal Resorption; Lipid Peroxides; Liver; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Proteins; Rats; Rats, Sprague-Dawley; Reference Values; Thiobarbituric Acid Reactive Substances

Three groups of five beagle bitches were treated three times a day with natural prostaglandin F2 alpha (PGF2 alpha) at a dosage of either 20 micrograms kg-1 bodyweight (days 5-8 of metoestrus), 50 micrograms kg-1 bodyweight (days 5-11 of metoestrus) or 20 micrograms kg-1 bodyweight after detection of pregnancy (days 20-21 after ovulation) for 7 days. A dose of 20 micrograms PGF2 alpha kg-1 bodyweight administered during the early luteal stage could not induce a reliable decrease of progesterone concentrations, while injections of 50 micrograms PGF2 alpha kg-1 bodyweight beginning before implantation resulted in arrest of luteal progesterone production and prevention of nidation in all five bitches. The application of 20 micrograms PGF2 alpha kg-1 bodyweight shortly after implantation induced functional arrest of corpora lutea and led to embryonic or fetal resorption in all cases. In general, the luteolytic effect of low PGF2 alpha doses was insufficient because of the recovery of the corpora lutea seen in nearly all bitches and the prolonged process of embryonic or fetal resorption that increase the risk of uterine disease.

Topics: Abortion, Induced; Animals; Corpus Luteum; Dinoprost; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Embryo Implantation; Embryo Loss; Embryonic Development; Female; Fetal Resorption; Injections, Subcutaneous; Pregnancy; Progesterone

Fourteen unvaccinated and seronegative ewes were experimentally infected with bovine virus diarrhoea virus around day 60 of pregnancy. Two other groups of pregnant ewes served as control animals. The animals were followed with ultrasound scanning to study the status of the fetus and with frequent blood sampling for analysis of progesterone and 15-keto-13,14-dihydro-PGF2 alpha, two hormones that could reflect the propagation of the infection. The unvaccinated ewes responded to the infection with abortion, resorption of the fetus, mummification or no changes at all. The endocrinological changes reflected in a most adequate way the pathological changes in the uterus. Detailed endocrinological studies can contribute to the understanding of the pathogenesis of some infectious diseases that affect reproduction.

Topics: Abortion, Veterinary; Animals; Bovine Virus Diarrhea-Mucosal Disease; Cattle; Cattle Diseases; Dinoprost; Female; Fetal Resorption; Fetal Viability; Pregnancy; Pregnancy Complications, Infectious; Progesterone; Prostaglandins F; Sheep; Sheep Diseases; Ultrasonography

Calcium channel blockers have been advocated as potential therapeutic agents in the management of premature labor. In the present study, the class of intracellular calcium antagonistic methylenedioxyindenes (MDIs) was investigated for potential antiabortifacient activity in mice. Pretreatment of pregnant mice from day 15 of gestation with the MDIs did not afford protection against the abortifacient effect of prostaglandin F2alpha administered from day 17 of gestation. The MDIs demonstrated embryotoxic and fetotoxic activity as shown by a significant increase in the incidence of resorptions and stillbirths. Similar embryotoxicity was previously reported for the calcium channel blockers. It appears doubtful that any of the calcium antagonists so far examined will be clinically useful in the management of premature labor.. 2 intracellular calcium antagonists with weak membrane calcium channel blocking activity were tested for antiabortifacient and embryotoxic effects in mice. The compounds were 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene (pr-MDI) and cis-2-n-butyl-3-dimethylamino-5,6-methylenedioxindan (cis-H-bu-MDI). Charles River CD-1 mice treated intramuscularly with saline (controls), or Pgf2alpha twice daily to induce premature abortion starting on day 17 of gestation, with 15 or 25 mg/kg cis-H-bu-MDI. or 70 mg/kg/pr-MDI. the LD50 for cis-H-bu-MDI was 75 mg/kg (single intramuscular dose). The compounds had no effect on premature delivery. They significantly decreased numbers of live-born pups, however, counted as the difference between implantation sites and recovered live or stillborn pups. There were no malformations, maternal toxicity or detrimental effects of survival or term-born progeny. These calcium antagonists appear to be of no value in the management of premature labor.

Topics: Abortifacient Agents; Abortion, Spontaneous; Animals; Dinoprost; Female; Fetal Resorption; Indenes; Mice; Pregnancy; Prostaglandins F

The influence of PGF2 alpha on pregnancy and fetal outcome was investigated in the hamster. Following subcutaneous treatment with 50, 100, 200, 400, and 800 micrograms PGF2 alpha prenatal loss was significantly increased only at the highest dose level. The offspring of the treated animals were all alive and normal. Fetal weight was not affected. However, following intravenous injection of 100 and 200 micrograms PGF2 alpha there was a significant reduction in fetal weight, and at the 400 micrograms dose level an increase in fetal indicate that PGF2 alpha is not teratogenic in hamsters despite the apparent greater sensitivity of the hamster embryo to prostaglandin.

Topics: Animals; Body Weight; Cricetinae; Dinoprost; Dose-Response Relationship, Drug; Female; Fetal Resorption; Fetus; Injections, Intravenous; Injections, Subcutaneous; Pregnancy; Pregnancy, Animal; Prostaglandins F