Teratogenic IgG From Sera of Women With Spontaneous Abortions Seem to Induce Anomalies and Yolk Sac Damage in Rat Embryos. A Possible Method to Detect Abortions of Immunologic Origin

Abir, Ronit; Ornoy, Asher

doi:10.1111/j.1600-0897.1996.tb00013.x

Cited by 12 publications

(11 citation statements)

References 18 publications

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“…7 Furthermore, similar pathological effects were observed in rat embryos cultured in sera from women with SLE, suggesting that immunological factors associated with SLE could be at least partially responsible for pregnancy loss in these women. 8 These same sera were used to investigate their effects also on placental explants.…”

Section: A Mechanismmentioning

confidence: 50%

Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS

Schwartz

Shoenfeld²,

Barzilai

et al. 2007

Lupus

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Systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS) are autoimmune diseases causing recurrent pregnancy loss. We hypothesized that anti-phospholipid antibodies (aPL), but not anti-Ro and anti-La antibodies, might have a role through direct placental damage. We cultured human placental explants in sera from women with SLE/PAPS with different antibodies. These sera were found to reduce placental growth and increase trophoblastic apoptosis. No effect was found on estradiol or progesterone secretion, but inhibition in betahCG secretion was detected. BetahCG was reduced in women with a history of recurrent pregnancy loss or thromboembolic events, and was also the most sensitive marker when examining the effects of specific antibodies. High titers of aPL were found to cause the largest reduction in betahCG. Anti-Ro and anti-La did not induce placental damage. A strong correlation was found between the rise in the number of different antibodies in the sera and the incidence of recurrent pregnancy loss, which was also accompanied by a decline in the betahCG levels. In conclusion, aPL, but not anti-Ro or anti-La, may cause placental damage in vitro. Thus betahCG levels might constitute a predictive marker for the risk of placental damage and pregnancy loss in women with SLE/PAPS.

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Section: A Mechanismmentioning

confidence: 50%

Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS

Schwartz

Shoenfeld²,

Barzilai

et al. 2007

Lupus

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“…(Ergaz et al, 2010). A high rate of anomalies in embryos cultured in sera from women with recurrent spontaneous abortions (Abir et al, 1994) or following the addition to the culture medium of purified IgG from SLE and APLs patients (Abir & Ornoy, 1996), differed from the study using sera obtained from non-pregnant patients in remission, where there was no increase in the rate of anomalies compared to controls. It can be speculated therefore, that the teratogenicity of the sera reflected the patient's high-activity disease state (Clowse et al, 2005).…”

Section: The Embryotoxicity Of Oxidative Stressmentioning

confidence: 87%

“…The embryos are cultured for 28-48 hours at 37°C in rotating bottles, and supplemented with gas mixtures: day-1: 20% Oxygen, 75% N2, 5% CO2, and day-2: 40% oxygen, 55% N2, and 5% CO2. After 28-48 hours of culture the embryos are examined under a dissecting microscope and scored according to the method described by Brown et al (Brown & Fabro, 1981) and us (Abir & Ornoy, 1996, Abir et al, 1994. Only embryos with a beating heart are examined for yolk sac size and circulation, axial rotation, neural tube closure, presence of telencephalic vesicles, optic and otic vesicles, number of somites, body size, and presence of gross anomalies.…”

Section: In Vitro Development Of Early Somite Stage Rat Embryos In Cumentioning

confidence: 99%

Embryonic and Placental Damage Induced by Maternal Autoimmune Diseases - What Can We Learn from Experimental Models

Ergaz¹,

Ornoy²

2012

Systemic Lupus Erythematosus

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Systemic Lupus Erythematosus 186 antibodies are typically found among the patients. Complement activation was shown to play a role in antiphospholipid antibody-mediated fetal loss associated with inflammatory process, when C4d, a degradation product of C4 was demonstrated in human placenta of SLE patients (Cohen et al., 2011), as well as diminished number of T regulatory cells, associated with pregnancy loss and pre-eclampsia (Tower et al., 2011). Circulating microparticles that expose phospholipids in the outer membrane and induce coagulation via tissue factor have been associated with lupus anticoagulants and poor obstetric outcome (Alijotas-Reig et al., 2009). Other reports indicate that enhanced oxidative stress could be linked to autoimmune diseases; however, there is lack of data about anti oxidant status of the placenta and embryos during pregnancy in women suffering from autoimmune diseases. 2. The role of experimental animal studies in evaluation of pregnancy complications among women suffering from autoimmune diseases As more than one mechanism of pathogenesis exists for fetal damage in autoimmune diseases, experimental animal models can be used to isolate the different causative effects. Evaluation of the role of different antibodies and molecules can be obtained by direct injection or induction of antibodies production in the pregnant animals and evaluation of the resultant effect on the embryos and fetuses. In such case the effect is evaluated in normal animals rather than being secondary to an autoimmune disease. Previous published studies revealed fetal damage induced by various antibodies. A smaller litter size was demonstrated after the injection to pregnant BALB/C mice with a human cytomegalovirus-peptide-induced monoclonal antiphospholipid (Gharavi et al., 2004). Fetal heart block and bradycardia were evidenced in a murine model as a result of maternal autoantibodies to Ro and La antigen induced by maternal immunization (Suzuki et al., 2005). In addition maternal immunization with DNA memitope in mice led to the induction of autoantibodies that bind DNA and the N-methyl-D-aspartate receptor in the maternal circulation leading to increased neocortical cell death in the fetal brain and subsequent delayed acquisition of neonatal reflexes and cognitive impairments in the adult offspring. In this model the antibodies that were detected in the fetal neocortex outside of blood vessels evidenced their transport through fetal circulation until binding to the fetal brain (Lee et al., 2009). We previously found that the immunization of BALB /C mice with mouse laminin-1 was followed by the development of anti-laminin-1 antibodies. A double fetal resorption rate and lower fetal and placental weight was found in the laminin-1 immunized group compared with controls. Resorption rate was highest in the subgroup of animals with very high levels of anti-laminin-1 (Matalon et al., 2003). Other molecules were also found to have direct embryotoxic effects. The injection of a low-molecular weight fraction of boiled h...

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“…Whole rat embryos were prepared as described previously and modified in our laboratory. 24,25 The embryos were cultured for 28 h at 37 C in rotating bottles. The gas mixture for the first day contained 20% O 2 , 75% N 2 , 5% CO 2 , and the second day (for the last 4 h in culture) 40% O 2 , 55% N 2 , and 5% CO 2 .…”

Section: Culture Of Early Somite Rat Embryosmentioning

confidence: 99%

The embryotoxicity of sera from patients with autoimmune diseases on post-implantation rat embryos in culture persists during remission and is not related to oxidative stress

Ergaz¹,

Mevorach

Goldzweig

et al. 2010

Lupus

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We evaluated the embryolethality and embryotoxicity of sera from patients suffering from autoimmune diseases during remission on post-implantation rat embryos cultured on these sera and determined the association between the patients' clinical history, high blood levels of specific antibodies, medications, and oxidative stress parameters. One hundred and eighty, 10.5-day-old rat embryos were cultured in their yolk sacs in 33 sera of systemic lupus erythematosus (SLE)/antiphospholipid syndrome (APS) patients, and compared with 84 embryos cultured in rat sera and 88 embryos cultured in control human sera. The sera proved to be lethal and embryotoxic but not teratogenic resulting in smaller yolk sacs and embryos, lower protein level and lower developmental score. Significantly less embryos cultured in 'toxic' SLE/APS sera had peak 2 of low molecular weight antioxidants (LMWA) wave, implying a delayed maturation of the antioxidant defense. Lower peak 1 of LMWA correlated with a history of recurrent abortions. Embryonic levels of superoxide dismutase (SOD) and catalase (CAT) did not correlate with sera toxicity, patients' clinical history or specific antibodies. We conclude that SLE/APS patients' clinical remission did not prevent death or developmental delay accompanied by later appearance of peak 2 of LMWA in post-implantation rat embryo cultures. The normal levels of the antioxidant enzymes evaluated may indicate that sera toxicity is not related to oxidative stress.

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Teratogenic IgG From Sera of Women With Spontaneous Abortions Seem to Induce Anomalies and Yolk Sac Damage in Rat Embryos. A Possible Method to Detect Abortions of Immunologic Origin

Abstract: The serum and the IgG fraction from women with habitual abortions can be tested in whole embryo culture to evaluate the embryonic and yolk sac damage. On this basis it may be possible to detect the women in whom the habitual abortions result from immunological rejection.

Cited by 12 publications

References 18 publications

Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS

Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS

Embryonic and Placental Damage Induced by Maternal Autoimmune Diseases - What Can We Learn from Experimental Models

The embryotoxicity of sera from patients with autoimmune diseases on post-implantation rat embryos in culture persists during remission and is not related to oxidative stress

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