Repeated Abortion Affects Subsequent Pregnancy Outcomes in BALB/c Mice

Abstract

AimIn this study, we aimed to establish a mouse model of repeated medical termination of pregnancy in order to determine subsequent outcomes.MethodsA model of mifepristone (RU 486)-induced medical abortion was established in BALB/c mice to facilitate the investigation of the impact of medical abortion on subsequent pregnancies, including litter sizes and newborn birth weights. Pregnant mice were sacrificed to examine midterm pregnancy status, investigate the frequency of fetal resorption, and measure placental function gene expression by real-time PCR and immunohistochemistry. Offspring liver mRNA was harvested for real-time PCR to determine gene expression and assess the effects of abortion on offspring development.ResultsMice subjected to 2 previous medical abortions experienced spontaneous abortions in subsequent pregnancies. Medical abortion caused reduced reproductive capacity and affected placental dysfunction, with reduced expression of tissue factor (TF) and genes encoding proteins involved in metabolic functions relevant to pregnancy, such as 11β-hydroxysteroid dehydrogenase 1/2 (11β-HSD1/2) and glucocorticoid receptor (GR). Reduced expression was also observed for platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF). In offspring from subsequent pregnancies, genes involved in lipid metabolism, which may enhance key lipid transcription factors, such as PPARA and PPARG, as well as GR/11β-HSD1, were downregulated in the liver. In addition, the sperm motility of the F1 males reduced.ConclusionRepeated medical abortion impaired the reproductive function of female mice, significantly affecting the outcomes of subsequent pregnancies. The impact of repeated abortions on the offspring of subsequent pregnancies was also noteworthy and deserves further exploration. Thus, this model provides a useful means to study the mechanisms underlying the above phenomena, which will ultimately benefit the health of women and their children.

Aneuploidy in Early Miscarriage and its Related Factors

“…BALB/c mice experiment result showed that repeated early medical abortions led to spontaneous abortion and pregnancy loss during subsequent pregnancies. [ 21 ] In humans, artificial abortion might be associated with an increased risk of first-trimester miscarriage in subsequent pregnancies. To indirectly determine whether artificial abortion is a cause of spontaneous abortion of subsequent pregnancy, we compared the rate of aneuploidy/polyploidy according to the number of previous artificial abortions.…”

Baicalin can attenuate the inhibitory effects of mifepristone on Wnt pathway during peri-implantation period in mice

“…Mifepristone is one kind of abortion medicines and commonly used for animal abortion model. According to the reports [16][17][18], the doses of mifepristone at 3.2-4.8 mg/kg BW can markedly decrease the average number of embryos in mice. In our pretest, we injected subcutaneously the different doses (3.2, 4.0 and 4.8 mg/kg BW) of mifepristone to Kuming mice on day 4 of the pregnancy, and found that the average number of embryos in mice administered with 4.0 and 4.8 mg/kg BW of mifepristone decreased (8.1 AE 2.85 embryo numbers/per mouse or 6.4 AE 1.97 embryo numbers/per mouse; p < 0.05; n = 8).…”

Mifepristone Treatment in Pregnant Murine Model Induced Mammary Gland Dysplasia and Postpartum Hypogalactia

“…Previous reports suggested that mifepristone administration at doses of 1.25-2.50 mg/kg BW on Pd4 had no impact on the reproduction of mice (Huang et al, 2005;Lv et al, 2012;Chen et al, 2015;Yang et al, 2016). However, mifepristone administration at doses of 0.30-2.00 mg/kg BW at approximately Pd8.5 caused 60-100% of abortions in mice (Szekeres-Bartho et al, 1997;Lv et al, 2012). Mifepristone treatment at doses of 0.40-12.50 mg/kg BW during late pregnancy (Pd14-Pd19) induced preterm labor in mice, with abortion rates of 66-100%.…”

“…A previous study in mice reported that the ducts from the nipples and buds were beginning to appear along the smaller ducts on Pd2 or Pd3; on Pd6, alveoli formation was taking place along all the ducts; from Pd7 to Pd12, the growth and budding of mammary gland proceed steadily, and the alveoli developed thickly along ducts until Pd12 (Cole, 1933). Researchers verified that administration of mifepristone at doses of 1.25-2.50 mg/kg BW on Pd4 had little effect on the litter size in mice (Huang et al, 2005;Lv et al, 2012;Chen et al, 2015), whereas when mifepristone was administrated at doses of 0.30-2.00 mg/kg and 0.401-2.50 mg/kg, respectively, on Pd8.5 and on Pd14-19, it induced more than 60% of abortions (Szekeres-Bartho et al, 1997;Lv et al, 2012). Based on the time points of mammary gland development, and the dose range of mifepristone that induce abortion in the studies described above, we administrated mifepristone on Pd4 (0.80, 1.20, 1.60, 2.00, and 2.40 mg/kg BW), Pd8 (0.20, 0.40, 0.60, 0.80, and 1.00 mg/kg BW), and Pd12 (0.10, 0.20, 0.30, 0.40, and 0.50 mg/kg BW) in a pilot study to identify the optimum mifepristone dosage for these time points.…”