The Effects Of Serum From Women With Miscarriages On The In Vitro Development Of Mouse Preimplantation Embryos

Abstract

It is generally believed that some human miscarriages result from embryotoxic factors existing in the sera. To study the embryotoxicity of such sera, 3.5-day-old mouse blastocysts were cultured for 72 h on 80% sera from different groups of women. After 72 h there was no blastocystic development in 53.2% of the cases grown on sera from women after two or more miscarriages, and none in 33.6% of the blastocysts grown on sera from women after one miscarriage, as compared with 8.2% and 12% respectively on control sera. Sera from women with miscarriages were divided into 'high risk' (50% or more embryotoxicity) and 'low risk' (less than 50% embryotoxicity) sera. The 'high risk' sera from two or more miscarriages caused an average of 72.1% undevelopment, while the 'low risk' sera (less than 50% embryotoxicity) from the same group caused 33.6% undevelopment. The 'high risk' sera from one miscarriage were embryotoxic to 55.8% of the blastocysts and the 'low risk' sera from the same group caused only 8.7% undevelopment. No significant differences were found in the mean serum concentrations of folic acid, zinc and copper of many of the experimental groups, in comparison with controls. The embryotoxic factor/s which exist in the 'high risk' sera from women with miscarriages are still not known.

Luteal phase serum cell-free DNA as a marker of failed pregnancy after assisted reproductive technology

“…Embryotoxic factors have been detected in the sera of patients with recurrent spontaneous abortions (RSA) or endometriosis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). About 24% (8,10) to 70% (2) of the sera of RSA patients and 0% (9) to 100% (7) of the endometriosis patients were found to be embryotoxic.…”

The Effects of IgG Purified from Women with SLE and Associated Pregnancy Loss on Rat Embryos in Culture

“…To demonstrate direct effects of the antibodies on embryos, several investigators have exposed embryos in in vitro systems to sera of women with recurrent abortions. Oksenberg and Brautbar 13 and Abir et al 14 . in our laboratory, have demonstrated the embryotoxic effects of sera from women with spontaneous abortions on preimplantation mouse embryos.…”

“…Many studies claimed that sera from women with SLE and from women with recurrent abortions were embryotoxic and teratogenic in vitro 13 –15 , 17 , 19 , 23 . However there seems to be no increase in the rate of anomalies in offspring of SLE and APS patients.…”

“…After that stage, growth inhibition might be a more common problem except for cleft palate that may be induced later. As many studies claimed that the embryotoxic factor is an IgG antibody, 13 , 14 , 19 , 23 , 26 we decided to analyze the direct effects of IgG purified from SLE and RPL patients on 11.5‐day old‐rat embryos, at a stage where malformations are less expected but growth inhibition can be analyzed. IgG purified from SLE and RPL indeed inhibited yolk sac diameter and ECRL in rat embryos in culture, in comparison with NIgG that was purified from healthy women.…”

Validation of an Embryotoxicity Assay

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Culture of mouse embryos has served as a tool for identifying these embryotoxins in human serum. I been suggested as a cause for reproductive failure because sera from some women with recurrent pregnancy 10SS,4,5,8,9,11.I3, 16 unexplained infertility,5,16 and infertility associated with endometriosis 14 inhibit growth of mouse embryos in vitro. Although the mouse blastocyst assay has been proposed to provide a basis for a new classification of idiopathic recurrent spontaneous abortion and act as an indicator of those women likely to respond to immunotherapy," the clinical utility of the embryotoxicity assay has been controversial.…”