Roles of Yangxue Antai prescription in improving endometrial epithelial-mesenchymal transformation and decidualization in recurrent spontaneous abortion mice by regulating autophagy

doi:10.19803/j.1672-8629.20240061

Abstract

Abstract: Objective To explore the role of Yangxue Antai prescription in improving endometrial epithelial-mesenchymal transformation (EMT) and decidualization in mice with recurrent spontaneous abortion (RSA) by regulating autophagy. Methods An RSA mouse model with kidney deficiency and blood stasis was established before the normal pregnant mice were intraperitoneally injected 2 mg·kg^-1 rapamycin (Rapa) solution or 15 mg·kg^-1 3-methyladenine (3-MA) solution, respectively; RSA mice, Rapa mice and 3-MA mice treated with the same method were also set up, and the concentration of 28.08 g·kg^-1 of Yangxue Antai Prescription was given at the same time for intervention, then the endometrium of the mice was collected. The expressions of EMT-related proteins E-cadherin, Vimentin, N-cadherin, and Fibronectin, as well as deciduation-related proteins BMP2, HOXA10, PRL, and IGFBP1 were measured by Western blot. Results Compared with the normal pregnancy group, the expression of E-cadherin in the endometrium of mice in the RSA group was significantly increased, while the expressions of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly decreased. The expression of E-cadherin in the endometrium of the Rapa group was significantly increased, while those of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly decreased. The protein expression of E-cadherin in the endometrium of the 3-MA group was significantly decreased while that of HOXA10 was significantly increased. Compared with the RSA group, the expression of E-cadherin in the the endometrium of mice in the RSA+ YXAT group was significantly decreased, while the expressions of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly increased. Compared with the Rapa group, the expression of E-cadherin in the endometrium of mice in the Rapa+ YXAT group was significantly decreased, while those of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly increased. Conclusion Yangxue Antai prescription can inhibit autophagy, promote EMT and decidualization process of the endometrium of pregnant mice, and reduce abortion rate.

Key words: Yangxue Antai prescription, rapamycin, 3-methyladenine, embryo implantation, recurrent spontaneous abortion, autophagy, epithelial-mesenchymal transformation, decidualization, herbal compounding, mice

CLC Number:

R984

YAO Weijie, YAN Shiqi, YUAN Sisi, GONG Leilei, FENG Xin. Roles of Yangxue Antai prescription in improving endometrial epithelial-mesenchymal transformation and decidualization in recurrent spontaneous abortion mice by regulating autophagy[J]. Chinese Journal of Pharmacovigilance, 2024, 21(5): 547-552.

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.zgywjj.com/EN/10.19803/j.1672-8629.20240061

https://www.zgywjj.com/EN/Y2024/V21/I5/547

References

[1] Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, Chinese Expert Consensus Group on Diagnosis and Management of Recurrent Spontaneous Abortion. Chinese expert consensus on diagnosis and management of recurrent spontaneous abortion (2022)[J]. Chinese Journal of Obstetrics and Gynecology(中华妇产科杂志), 2022, 57(9): 653-667.
[2] ESHRE Guideline Group on RPL, Bender Atik R, Christiansen OB, et al. ESHRE guideline: recurrent pregnancy loss[J]. Hum Reprod Open, 2018(2): hoy004.
[3] SHI S, TAN Q, LIANG J, et al.Placental trophoblast cell-derived exosomal microRNA-1290 promotes the interaction between endometrium and embryo by targeting LHX6[J]. Mol Ther Nucleic Acids, 2021, 26: 760-772.
[4] PAN D, LI J, HE YY.Study on the collation of ancient books of traditional Chinese medicine for recurrent abortion[J]. Hunan Journal of Traditional Chinese Medicine(湖南中医杂志), 2020, 12(36): 108-110.
[5] ZHANG J, NI S, LI J.Effect of Bushen Huoxue Formula on expression of VEGF/PI3K/Akt pathway in decidua of mice with recurrent abortion[J]. Shanghai Journal of Traditional Chinese Medicine(上海中医药杂志), 2021, 2(55): 82-89.
[6] WEI S.Impact of Bushen Huoxue formula on serum VEGF and TGF-β1 in unexplained recurrent spontaneous abortion and non-pregnant patients with kidney deficiency and blood stasis type at the late secretory phase[J]. Journal of Guangzhou University of Traditional Chinese Medicine(广州中医药大学学报), 2021, 38(9): 1846-1855.
[7] HE JQ, LI MJ, WANG YW, et al.Intervention of integrated Chinese and western medicine on prethrombotic state in recurrent spontaneous abortion with Yangxue Antai granules[J]. World Journal of Integrated Traditional and Western Medicine(世界中西医结合杂志), 2014, 9(6): 620-623.
[8] LI ET, LI MJ, GAO AP, et al.Effect of Yangxue Antai granule in prevnting and treating habitual abortion and its effect on short life T-suppressor Cell[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2000, 20(4): 248-250.
[9] MOSER G, WEISS G, SUNDL M, et al.Extravillous trophoblasts invade more than uterine arteries: evidence for the invasion of uterine veins[J]. Histochem Cell Biol, 2017, 147(3): 353-366.
[10] LAI R, JI L, ZHANG X, et al.Stanniocalcin2 inhibits the epithelial-mesenchymal transition and invasion of trophoblasts via activation of autophagy under high-glucose conditions[J]. Mol Cell Endocrinol, 2022, 547: 111598.
[11] WANG J,DING J,ZHANG S,et al.Decreased USP2a expression inhibits trophoblast invasion and associates with recurrent miscarriage[J]. Front Immunol 2021, 12: 717370.
[12] TANG SL, LIANG X, LI RX, et al.Effects of Shoutai Pills on EMT of embryonic trophoblasts in recurrent spontaneous abortion mice[J]. Journal of Beijing University of Traditional Chinese Medicine(北京中医药大学学报), 2023, 46(8): 1139-1149.
[13] BIRGIT G, BROSENS JJ.Cyclic decidualization of the human endometrium in reproductive health and failure[J]. Endocr Rev, 2014, 35(6): 851-905.
[14] ZHAO Y, WEN AM, LIANG JL, et al.Clinical study in serum β-HCG, progesterone, estradiol tests and abdominal ultrasound examination to predict outcomes for early intrauterine pregnancy with vaginal bleeding[J]. Journal of SUN YAT-SEN University(Medical Sciences)(中山大学学报医学科学版), 2015, 36(1): 6.
[15] YANG Q.PANX1 affects endometrial decidualization in recurrent implantation failure patients by regulating eATP concentration[D]. Nanchang: Nanchang University, 2023.
[16] LIU HM, XIONG X, WEN X, et al.The molecular mechanism of bisphenol a regulating the expression of endometrial decidualization molecular marker HOXA10 through MLL1[J]. Chinese Journal of Reproductive Health(中国生育健康杂志), 2023, 34(1): 60-65.
[17] LEE KY, JEONG JW, WANG J, et al.Bmp2 Is critical for the murine uterine decidual response[J]. Mol Cell Biol, 2007, 27(15): 5468-5478.
[18] SATO M, SEKI T, KONNO A, et al.Rapamycin activates mammalian microautophagy[J]. J Pharmacol Sci, 2019, 140(2): 201-204.
[19] DIKIC I, ELAZAR Z.Mechanism and medical implications of mammalian autophagy[J]. Nat Rev Mol Cell Biol, 2018, 19(6): 349-364.
[20] ZHANG Y, GAO R F, ZHANG L, et al.AMPK/mTOR downregulated autophagy enhances aberrant endometrial decidualization in folate-deficient pregnant mice[J]. Journal of Cellular Physiology, 2021, 236(11): 7376-7389.