Decreased NDRG1 expression is associated with pregnancy loss in mice and attenuates the in vitro decidualization of endometrial stromal cells

Meng, Nan; Yang, Qian; He, Yaping; Gu, Wenwen; Gu, Yu; Zhen, Xing-Xing; Wang, Jianmei; Zhang, Xuan; Sun, Zilong; Wang, Jian

doi:10.1002/mrd.23238

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…LINC00240 promotes cell proliferation, invasion, and migration in gastric and cervical cancer (81,82), and miR-182 suppresses FOXO1 expression in endometrial cancer cells (83). In addition, N-myc downregulated gene 1 (NDRG1) directly affects pregnancy in mice, and reduced NDRG1 expression has been reported in decidual samples from patients with recurrent miscarriage (84). Thus, the LINC00240/miR-182/NDRG1 axis may also play important roles in endometrial receptivity.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Kim

Han

et al. 2021

Exp Ther Med

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Successful embryo implantation is the first step for establishing natural pregnancy and is dependent on the crosstalk between the embryo and a receptive endometrium. However, the molecular signaling events for successful embryo implantation are not entirely understood. To identify differentially expressed transcripts [long-noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs] and competing endogenous RNA (ceRNA) networks associated with endometrial receptivity, the current study analyzed gene expression profiles between proliferative and mid-secretory endometria in fertile women. A total of 247 lncRNAs, 67 miRNAs and 2,154 mRNAs were identified as differentially expressed between proliferative and mid-secretory endometria. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these differentially expressed genes were significantly enriched for 'cell adhesion molecules.' Additionally, 98 common mRNAs were significantly involved in tryptophan metabolism, metabolic pathways and FoxO signaling. From the differentially expressed lncRNA/miRNA/mRNA ceRNA network, hub RNAs that formed three axes were identified: The DLX6-AS1/miR-141 or miR-200a/OLFM1 axis, the WDFY3-AS2/miR-135a or miR-183/STC1 axis, and the LINC00240/miR-182/NDRG1 axis. These may serve important roles in the regulation of endometrial receptivity. The hub network of the current study may be developed as a candidate marker for endometrial receptivity.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Kim

Han

et al. 2021

Exp Ther Med

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“…Previous studies have shown that impaired decidualization is a crucial pathological link of URSA. For instance, Meng et al found impaired decidualization in URSA featured with significantly decreased level of NDRG1 which was physiologically accumulated in the primary decidual region and contributed to the embryo implantation ( Meng et al, 2019 ). In our studies, we also found impaired decidualization in URSA patients manifested by decreased mRNA levels of PRL and IGFBP1, which was consistent with the findings mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Mechanism of Bushen Huoxue Decotion on Decidualization by Intervening Autophagy via AMPK/mTOR/ULK1: A Novel Discovery for URSA Treatment

et al. 2022

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Impaired decidualization was recognized as one of the crucial pathomechanisms accounting for unexplained recurrent spontaneous abortion (URSA). Currently, the exact molecular mechanism and targeted clinical decision are still in exploration. Bushen Huoxue decoction (BSHXD) has previously been proved effective in treating URSA, but its mechanism remains to be elucidated. This study aimed to explore the regulation mechanism of BSHXD in decidualization from its intervention in autophagy so as to rationalize its potential as a novel therapeutic regime for URSA. Decidua tissues were collected from patients with URSA and healthy pregnant women who underwent legal terminations for non-medical reasons at the first trimester. Besides, cell line T-hESCs was utilized to establish induced decidualization model, and were randomly divided into ESC group, DSC group, 3-MA group, AMPK siRNA group, scrambled siRNA group and AMPK siRNA + BSHXD group. Transmission electron microscopy, Monodansylcadaverine (MDC) assay, qRT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to evaluate the level of decidualization, autophagy and activation of AMPK signaling pathway in decidua tissues and cell experiments. Experiments on decidua tissues showed that decidualization was impaired in URSA with inhibited autophagy. Besides, pAMPK T172 and pULK1 S556 were decreased, and pmTOR S2448 and pULK1 S757 were increased. Cell experiments showed that the level of autophagy increased during induced decidualization, but when autophagy was inhibited, decidualization was impaired. In addition, AMPK/mTOR/ULK1 affected decidualization by mediating autophagy, and BSHXD improved decidualization through this mechanism. In conclusion, this study clarified that the inhibition of autophagy mediated by AMPK/mTOR/ULK1 was associated with impaired decidualization, and the intervention of BSHXD on this pathological process may be a vital mechanism for its treatment of URSA. This study laid the foundation for further research and application of BSHXD.

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“…Endometrial decidualization is characterized by the transformation of stromal cells into large round or polygonal decidual cells [ 17 ] and impaired endometrial decidualization is closely related to infertility, implantation failure, and miscarriage [ 18 – 20 ]. PK2 has been demonstrated to be involved in multiple physiological and pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of prokineticin 2 and its receptor in endometrium of recurrent implantation failure patients decreased the expression of MMP9 important for decidualization

Zhai

Chang

et al. 2022

Reprod Biol Endocrinol

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Background Studies have shown that abnormalities in the decidualization process were closely related to recurrent implantation failure (RIF). Prokineticin 2 (PK2) is a secreted protein with angiogenic and tissue remodeling functions but its role in the endometrium is unknown. Methods PK2 levels and its receptor PKR1 mRNA and protein levels in mid-secretory endometrium from normal and RIF women were examined by real-time PCR and western blotting, respectively. The effects of PK2 were evaluated by overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found different expression of Matrix metalloproteinase 9(MMP9) and lncRNA LUCAT1 by RNA-sequencing. The ability of PK2 to regulate LUCAT1 and MMP9 was verified in endometrial cells by real-time PCR and western blotting. Results Using endometrial biopsies from normal and RIF patients, we found increased expression of PK2, together with its receptor PKR1 in RIF patients. We then overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found decreased expression of Matrix metalloproteinase 9(MMP9), and increased expression of lncRNA LUCAT1. We verified the ability of PK2 to stimulate LUCAT1 and decrease MMP9 in endometrial cells. We further demonstrated that increased expression of a long noncoding RNA LUCAT1 and decreased expression of MMP9 in endometrial biopsies of patients with RIF. Thus, we highlighted the important role of PK2 and its receptor PKR1 in decidualization and RIF. Conclusion Prokineticin 2 and its receptor are important in endometrium decidualization. PK2 may affect endometrial decidualization through the LUCAT1- MMP9 pathway, thereby affecting embryo implantation.

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Decreased NDRG1 expression is associated with pregnancy loss in mice and attenuates the in vitro decidualization of endometrial stromal cells

Cited by 13 publications

References 35 publications

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Deciphering the Mechanism of Bushen Huoxue Decotion on Decidualization by Intervening Autophagy via AMPK/mTOR/ULK1: A Novel Discovery for URSA Treatment

Increased expression of prokineticin 2 and its receptor in endometrium of recurrent implantation failure patients decreased the expression of MMP9 important for decidualization

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