Effect of a single dose of mifepristone on expression of pinopodes in endometrial surface of mice1

Abstract

Aim: To investigate the effect of mifepristone (RU486) as a single dose on pinopodes expression in the endometrial surface of mice at the time of implantation. Methods: Pregnant mice in the treated four groups received mifepristone subcutaneously (0.1 mg) between 07:00 and 08:00 AM on Pd (day of pregnancy)1, Pd2, Pd3, and Pd4. Pregnant mice in the non‐treated group were used as controls. The uterine horns were collected randomly from two mice in each group between 21:30 and 22:00 PM on Pd4, and from another two mice of the same group between 09:30 and 10:00 AM on Pd5. The specimens were examined by scanning electron microscopy for the detection of pinopodes. Results: When mifepristone was given on Pd1, developing and fully developed pinopodes were observed, but the expression was markedly reduced compared to the control group. When mifepristone was administered on Pd2, only a few developing pinopodes were present. When mifepristone was administered on Pd3, developing pinopodes were observed. When mifepristone was administered on Pd4, different development stage pinopodes were present in specimens collected between 21:30 and 22:00 PM on Pd4, but no pinopodes was observed in specimens taken between 09:30 and 10:00 AM on Pd5. Conclusion: These findings suggest that administration of a single dose of RU486 subcutaneously on Pd1, Pd2, Pd3, and Pd4 might play a role in inhibiting development and maturation of endometrium, hence affecting embryo implantation in mice.

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

“…But the ovaries were not affected, and the estradiol/progesterone concentrations in serum were not significantly changed. Huang et al [17] found that subcutaneous administration of a single dose of mifepristone 0.10 mg mouse À1 on Pd1, Pd2, Pd3 and Pd4 respectively inhibited the development and maturation of the endometrium, thus affecting the embryo implantation. Lai and Zhang [20] found that the levels of Dkk1 mRNA and protein in mifepristone group were significantly higher than those in the control groups, suggesting that Dkk1 probably plays an important role in signal transudation of the embryo implantation, and its expression may be up-regulated by progestogen.…”

“…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

“…Mifepristone is an effective drug for termination of early pregnancy. 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).…”

“…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.…”

Effect of Zhuyun recipe on endometrial pinopode expression in mice with embryonic implantation dysfunction and ovulation stimulation

“…Pinopode deficiency in reproductive females undergoing in vitro fertilization (IVF) and embryo transfer treatment results in multiple implantation failures. Previous studies in humans have revealed that the window of implantation, which begins upon the formation of fully developed pinopodes, opens and closes earlier in females undergoing ovarian hyperstimulation for IVF compared with females with natural cycles ( 15 – 17 ). In addition, a low dose of mifepristone, which is administered as a progesterone (P4) receptor antagonist, restrains the development and maturity of pinopodes ( 18 ).…”