Enhancement of Endometrial Receptivity by <i>Cnidium officinale</i> through Expressing LIF and Integrins

Chung, Tae‐Wook; Park, Mi-Ju; Lee, Hoyoung; Kim, Keuk‐Jun; Kim, Cheorl-Ho; Choi, Hee‐Jung; Ha, Ki‐Tae

doi:10.1155/2019/7560631

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…Thus, LIF and integrin ανβ3 are used as indicators of the establishment of uterine receptivity. In our study, the downregulation of GLUT4 resulted in the defective glucose uptake of endometrial epithelial cells, which further led to impaired endometrial receptivity by inhibiting pinopode formation and the expressions of endometrial receptivity markers, LIF and integrin ανβ3, and then impaired implantation (Franasiak et al, 2014;Chung et al, 2019). In embryo transfer experiments, pretreatment of one side of the mouse uterine horns with GLUT4-siRNA also resulted in a reduced implantation rate, even if excellent embryos were selected for transfer.…”

Section: Discussionmentioning

confidence: 61%

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

et al. 2021

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GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1–4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epithelium in vivo or in vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs) in vitro or in vivo. In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA). In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανβ3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.

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Section: Discussionmentioning

confidence: 61%

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

et al. 2021

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“…Although assisted reproduction techniques (ART) have been widely used for the clinical treatment of infertility resulting from benign gynecological disorders or primary unexplained infertility, subsequent pregnancy rates remain unsatisfactory [4,7]. In traditional Eastern medicine, herbal medicines, acupuncture, and moxibustion are used to treat female infertility [8,9], and recently, due to accumulated scientific evidence, herbal medicine has emerged as an effective, complementary, alternative medicine for improving endometrial receptivity [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Although this prescription is used clinically to treat female infertility, experimental evidence obtained from in vitro and in vivo laboratory studies is lacking [ 6 ]. Mifepristone (also known as RU486) is a potent antiprogesterone agent, which can be used orally to induce abortion [ 16 ] or as an effective emergency contraceptive [ 17 ], and has often been used to induce embryo implantation failure or polycystic ovary syndrome in experimental animal models [ 10 , 18 , 19 ]. In the present study, we investigated the effects of a BCB water extract on endometrial receptivity and embryo implantation under normal conditions and in an RU486-induced mouse model of implantation failure.…”

Section: Introductionmentioning

confidence: 99%

Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium

et al. 2020

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Background BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model. Methods In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues. Results BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. Conclusion These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.

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“…Recently, herbal medicine has emerged as complementary and alternative medicine as obtained scienti c evidence for its e cacy in improving endometrial receptivity [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it decreased production of human chorionic gonadotropin (hCG), which in turn results in decreased production of progesterone by the corpus luteum. RU486 has been often used to induce embryo implantation failure or polycystic ovary syndrome in experimental animal models [11,[17][18][19]].…”

Section: Introductionmentioning

confidence: 99%

Administration of Herb Formulation Enhanced Blastocyst Implantation via Iκb Activation in Mouse Endometrium

Jeon

Liu

Cai

et al. 2020

Preprint

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BackgroundBaelan Chagsang Bang (BCB), consisting of a mixture of 11 herbs, may be prescribed as a reproductive function supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Oriental Medicine. This study aimed to investigate the effects and mechanisms of action of water-extracted BCB on endometrial receptivity and blastocyst implantation in a mifepristone (RU486)-induced implantation failure model.MethodsIn in vitro, antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and DCFH-DA assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically. BCB was administrated from 7 days before pregnancy until the end of the experiment. They were housed with male mice until pregnancy was confirmed. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure.ResultsAdministration of the BCB water extract increased the number of newborn pups in BCB-treated mice compared to that of sham-treated mice and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein expression level of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression level of matrix metalloproteinases (MMPs) at the uterus implantation site was up-regulated in the BCB-treated group compared to that of the RU486-treated group. To determine the mechanisms of action of BCB, the anti-oxidative effect of BCB was examined via in vitro assay. The BCB water extract showed strong anti-oxidative effects in the DPPH assay and the superoxide anion free-radical scavenging activity assay.ConclusionOur findings provide evidence that BCB has therapeutic potential against poor endometrial receptivity.

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Enhancement of Endometrial Receptivity by Cnidium officinale through Expressing LIF and Integrins

Cited by 13 publications

References 31 publications

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium

Administration of Herb Formulation Enhanced Blastocyst Implantation via Iκb Activation in Mouse Endometrium

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