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Biomedical subjects

A Ornoy

Publications and source records attributed to A Ornoy.

206 records · Page 12Linked to original sources

The effect of sera from women with systemic lupus erythematosus and/or antiphospholipid syndrome on rat embryos in culture.

Women with systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (APLA) suffer from a high rate of recurrent abortions perhaps as a result of specific antibodies that may damage the conceptus. We studied the effects of sera from women with SLE--with or without--APLA and recurrent abortions on 10.5-d-old rat embryos in culture. This was compared to the results of culture on sera from control women and on rat sera. In addition, we studied sera from women with SLE with or without APLA after treatment with low doses of aspirin and glucocorticosteroids. Seventy-three percent of embryos cultured in sera from women with SLE with or without APLA were malformed in comparison to only 10.2% in embryos cultured on control sera and 5.4% in embryos cultured on rat sera. The rate of anomalies was reduced to 37.5% in embryos cultured on sera from women with SLE with or without APLA after treatment, as in 6 of 13 sera, the treatment reduced or prevented the occurrence of embryonic anomalies. When sera were divided in to low- and high-risk sera, the effect of treatment was even more significant, as the average percentage of embryonic anomalies per serum was reduced from 81.7 to 44.7%. Specific ultrastructural changes were found in the yolk sacs of the embryos cultured on the sera from women with SLE with or without APLA by transmission electron microscopy and by scanning electron microscopy. It seems that the rat embryo culture system may be an important clinical diagnostic tool to identify women with recurrent abortions in whom the etiology may be immunologic rejection of the embryo and to assess the efficacy of various treatment modalities.

Abnormalities, Drug-Induced↗

Is benzodiazepine use during pregnancy really teratogenic?

Benzodiazepines (BDs) have a widespread use among people suffering from anxiety. These drugs easily cross the placenta and may affect the developing embryo and fetus. The literature is divided as to whether BD may cause an increase in spontaneous abortions or congenital anomalies. From the years 1988 to 1996, 756 women called the Israeli TIS concerning exposures to BD prior to or during pregnancy. Of 599 women who called us during pregnancy, we have follow-up information on 460 pregnancies (76.6%). The incidence of congenital anomalies (3.1%) was not different from that found in 424 control pregnancies (2.6%). There was a significantly higher incidence of induced abortions (14.1% vs. 4.7%, P = 0.00) and of spontaneous abortions (8.7% vs. 5.2%, P = 0.01). From an examination of our results, it does not appear that BD during pregnancy caused an increase in the incidence of birth defects. There was no specific defect in the offspring. The increase in the rate of induced abortions is probably related to the counseling of the callers, and the increase in spontaneous abortions seems to be a result of the lower gestational age at the time of counseling in the women exposed to BD. It is unknown whether BD could be responsible for developmental or behavioral problems, which are observed only at a later stage.

Abnormalities, Drug-Induced↗

Genetic and teratogenic effects of cancer treatments on gametes and embryos.

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.

Abnormalities, Drug-Induced↗

Transplacental effects of methylmercury chloride in mice with specific emphasis on the audiogenic seizure response.

Sabra mice were exposed to a single injection of 8 mg/kg body weight of methylmercury chloride on day 12 of their gestation. The mice were then sacrificed on day 19 and their fetuses were removed for examination. The fetal malformation rate was 8.6% with the most common anomaly being cleft palate. In another group, offspring who were exposed in utero to a single dose of 8 mg/kg methylmercury chloride were tested for their susceptibility to the audiogenic seizure response on days 28-31 after birth. There was a significant (p less than 0.05) increase (almost twofold) in the susceptibility of treated versus controls to this response, suggesting possible neurological damage.

Abnormalities, Drug-Induced↗

Embryotoxic effects of diabetes on pre-implantation embryos.

We describe the effects of metabolic diabetic factors and sera from diabetic animals and humans on the development of early pre-implantation mouse embryos. Our studies demonstrated that 20 to 24% of control mouse blastocysts failed to develop successfully when grown for 72 h in RPMI medium supplemented with 10% fetal bovine serum. D-glucose in concentrations greater than 3 mg/ml, insulin at concentrations of 0.5 and 1.0 IU/ml, glucagon in concentrations of greater than or equal to 10 micrograms/ml, beta-hydroxybutyrate in concentrations greater than 5 mg/ml, and acetoacetate at concentrations of greater than or equal to 10 micrograms/ml were all embryotoxic, the number of underdeveloped blastocysts rising to over 50%. The combination of these factors in relatively low concentrations was highly embryotoxic, especially when accompanied by hyperglycemia. The addition, to a control medium, of serum from nondiabetic rats (in concentrations of 20%) or of nondiabetic human serum (in concentrations of 50%) did not significantly change the rate of blastocystic development. Serum from streptozotocin-diabetic rats, in the same concentrations, increased the number of undeveloped embryos to 53%. With human diabetic sera the highest embryotoxic effect was found in type I diabetes with and without ketoacidosis. In type II diabetes, embryotoxic effects, although lower, were observed among all types studied [untreated, treated with insulin or with DAONIL (Hoechst, Germany)]. A high correlation was found between the number of undeveloped embryos and the blood concentrations of metabolic diabetic factors: glucose (in type I diabetes), beta-hydroxybutyrate (in type II diabetes untreated or treated with Daonil), acetoacetate (in insulin-treated type II diabetes), and HbA1c (in both insulin-treated and in Daonil-treated type II diabetes). The possible role of diabetic metabolic factors in causing increased risk of spontaneous abortions and infertility among diabetic women is discussed.

Animals↗