Establishment And Subsequent Pregnancy Outcomes Of Abortion Model Of BALB / C Mice Were Repeated

Aim:Medical or surgical abortion is one of the oldest, most commonly practiced, and most controversial induced procedure performed in the world. Repeated abortions account for a large portion of early pregnancy termination. But knowledge is lacking on risks of recurrent pregnancy after abortion, and other effects of abortion on subsequent pregnancy remain an important public health concern. The widely increasing trend of medical abortion and repeated abortions, particularly becoming frequent in an even younger population, critically require risk estimation. In this study, we aimed to establish a mouse model of the repeated medical termination of pregnancy and determine its subsequent outcomes.Methods:Mifepriston (RU486) medical abortion in BALB/c mice model was established to investigate the impact of medical abortion on subsequent pregnancy, including litter size and newborn birth weight. Pregnant mice were sacrificed to examine the mid-term pregnancy status and investigate the frequency of fetal resorption and placental function gene expression by real-time PCR and immunohistochemistry. Offspring liver mRNA was harvested for real-time PCR to determine the gene expression. Adult males from Fl generations of control and treatment groups were sacrificed to collect the testes and caudal epididymal sperm for further analysis, and investigated sexual function of Fl male. And we also investigated sexual function of female Fl generations.Results:Mice that previously experienced early medical abortion exhibited spontaneous abortion and pregnancy loss on subsequent pregnancy. Litter size and newborn birth weight of subsequent pregnancy were likewise adversely affected. On midgestation, spontaneous abortion occured during the subsequent pregnancy after medical abortion by RU486, but the level of progesterone and estrogen were no difference compared with control groups. We detected and analyzed metabolic gene expressions in midgestation placental and offspring liver. Medical abortion caused reduced reproductivity and affected placental dysfunction, with downregulation of tissue factor (TF), platelet endothelial cell adhesion molecule-1(CD31), vascular endothelial growth factor (VEGF), especially a panel of genes for proteins involved in metabolic functions relevant for pregnancy, such as 11β-hydroxysteroiddehydrogenase1/2(11β-HSD1/2), serine/threonine protein kinase1(SGK1) and glucocorticoid receptor (GR) expression were reduced. In the offspring, genes involved in lipid metabolism which might enhance key lipid transcription factors (PPARA and PPARG) and GR/11β-HSD1were down-regulated in the liver. We also found that F1female and male reduced their reproduction ability.Conclusion:We established an inbred model system investigating the impact of repeated first trimester mifepristone induced abortions, which led to subsequent pregnancy loss, affected placental function related gene expression, and F1generation development. This mechanism may involve epigenetic manipulation and merits further study. Thus, the model provides useful means to study the mechanism underlying the above phenomena, which will ultimately benefit the health of women and their children.