The Modified Bushen Antai Recipe Upregulates Estrogen and Progesterone Receptors at the Maternal-Fetal Interface in Pregnant Rats with Mifepristone-Induced Pregnancy Loss

Abstract

Background The modified Bushen Antai recipe (BSAT) is a centuries-old traditional Chinese medicine that we use in our center as a therapy against pregnancy loss. Our study aimed to explore the potential benefit and mechanism of BSAT in pregnant rats with mifepristone-induced pregnancy loss. Materials and Methods The signature compounds of the eight BSAT ingredients were analyzed by high-performance liquid chromatography (HPLC). The BSAT group (n = 8) was treated daily with 6.3 ml/kg BSAT from gestation day (D) 0.5 to 10.5 and once with 1.25 mg/kg mifepristone on D 10.5. Normal saline replaced BSAT in the model group (n = 8), and both BSAT and mifepristone in the control group (n = 8). Morphological and histological analyses were performed on D 13.5. Results BSAT contains eight medicinal ingredients including Cuscuta chinensis and Dipsacus asperoides. The HPLC analysis detected the signature compounds of seven medicinal ingredients in the extract. Embryo resorption rate in the BSAT group was significantly lower than that in the model group, although the number of surviving embryos was similar between the two groups. Hematoxylin and eosin (HE) staining suggested that the maximum cross-sectional area of the placenta and the area ratio of the placental labyrinth in the BSAT group were higher than those in the model group. Immunohistochemical (IHC) staining indicated that the expression of ki67, estrogen receptor alpha (ERα), and progesterone receptor (PR) in the placental labyrinth of the BSAT group was higher than that of the model group. Furthermore, the protein levels of ERα, PR, phospho-Akt/Akt, and phospho-Erk1/2/Erk1/2 in the BSAT group were higher than those in the control group. The mRNA levels of ERα and PR in the BSAT group were higher than those in the control group. Conclusions BSAT may induce estrogen and progesterone receptors by phosphorylation via the classic Akt and Erk1/2 signaling pathways in the maternal-fetal interface of pregnant rats, thereby reducing the pregnancy loss rate and improving the live birth rate.

Clinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed Abortion

“…P is the main biologically active progestin secreted by the ovary that binds to specific receptors in target tissues such as the endometrium and myometrium to maintain placental function [ 18 ]. It is also able to reduce the sensitivity of the uterine muscle to contraction to avoid abnormal uterine contractions during pregnancy [ 19 ]. E2 is an estrogen secreted by the placenta and ovaries, which can promote endometrial proliferation and lay the foundation for normal pregnancy, and its level in early pregnancy can reflect ovarian luteal function and the quality of the dominant follicle [ 20 ].…”

Dipsacus and Scabiosa Species—The Source of Specialized Metabolites with High Biological Relevance: A Review

“…Gao et al [62] proposed that Dipsaci radix and its main ingredient, akebia saponin D, may promote decidualization in pregnant women. Bushen Antai, a Chinese herbal medicine preparation containing Dipsaci radix, was found to reduce the pregnancy loss caused by mifepristone administration [183]. This preparation may stimulate estrogen and progesterone receptors through Akt and Erk1/2 signaling pathways in the maternal-fetal interface of pregnant rats.…”

Efficacy and safety of Yunkang oral liquid combined with conventional therapy for threatened miscarriage of first-trimester pregnancy a protocol for systematic review and meta-analysis

“…YKOL combined with conventional therapy for TMFP: A protocol for systematic review and meta-analysis and improving the live birth rate [17]. The reported mechanisms from modern researches of YKOL various components are as follows: Semen Cuscutae Chinensis and Dipsacales are reported to have steroid-like and hormone-like effects, maintaining the hormone balance of the pregnant mother [15]; Cibotii Rhizoma maintain immune balance [18]; Asini Corii Colla, which has always been used as a tonic, promotes blood circulation [19].…”

“…This effect is related to increasing the hormone levels of follicle stimulating hormone, luteinizing hormone, prolactin, progesterone, and estrogenic in serum and promoting the proteins expression of prolactin receptor, progesterone receptor, and estrogenic receptor in mouse decidua [ 13 – 16 ]. In addition, animal studies also have found that YKOL may induce estrogen and progesterone receptors by phosphorylation via the classic Akt and Erk1/2 signaling pathways in the maternal-fetal interface of pregnant rats, thereby reducing the pregnancy loss rate and improving the live birth rate [ 17 ]. The reported mechanisms from modern researches of YKOL various components are as follows: Semen Cuscutae Chinensis and Dipsacales are reported to have steroid-like and hormone-like effects, maintaining the hormone balance of the pregnant mother [ 15 ]; Cibotii Rhizoma maintain immune balance [ 18 ]; Asini Corii Colla , which has always been used as a tonic, promotes blood circulation [ 19 ].…”