Application of PRMT3 in diagnosis or treatment of recurrent spontaneous abortion

A spontaneous abortion and recurrent technology, applied in disease diagnosis, medical preparations containing active ingredients, diseases, etc., can solve the problems of limited function of PRMT3, achieve the effect of clear mechanism, inhibition of apoptosis, and promotion of apoptosis

Active Publication Date: 2021-07-13
SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to limited identified substrates, studies on the function of PRMT3 are still very limited

Method used

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  • Application of PRMT3 in diagnosis or treatment of recurrent spontaneous abortion
  • Application of PRMT3 in diagnosis or treatment of recurrent spontaneous abortion
  • Application of PRMT3 in diagnosis or treatment of recurrent spontaneous abortion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Analysis of PRMT3 expression in decidual tissue and decidual macrophages of normal pregnant women and patients with recurrent spontaneous abortion

[0028] Decidual cells comprise terminally differentiated uterine stromal cells (also known as decidual stromal cells) and numerous maternal immune cells, the major populations of which include uterine natural killer cells and macrophages. By Western blot analysis, we found that the expression level of PRMT3 protein in decidua tissue was significantly up-regulated. In order to further verify which type of decidual cells the expression of PRMT3 protein was up-regulated, we detected the protein expression level of PRMT3 in decidual stromal cells extracted from decidual tissue, uNK cells and macrophages by Western blot. The results showed that PRMT3 protein expression (1.358±0.2073vs 0.4888±0.08541, P=0.0002) was significantly up-regulated in decidual macrophages of RSA patients compared with normal pregnant women ( ...

Embodiment 2

[0029] Example 2: Inhibition of PRMT3 reduces HTR8 cell apoptosis

[0030] Decidual macrophages have many functions during pregnancy. Previous studies have shown that decidual macrophages perform a 'cleanup' function by engulfing apoptotic trophoblast cells, thereby preventing the activation of pro-inflammatory pathways in the decidua. In this study, we established a co-culture model of decidual macrophages and HTR-8 / SVneo cells through Transwell culture plates to explore the possible regulation of macrophages on trophoblast apoptosis. Decidual macrophages derived from RSA patients were sorted and purified by CD14 magnetic beads and cultured in the lower chamber of the Transwell plate, and HTR-8 / SVneo cells were spread in the upper chamber of the Transwell plate. The decidual macrophages in the lower chamber were divided into two groups. The decidual macrophages were stimulated with 200nM PRMT3 specific inhibitor SGC707 in the treatment group, and the control group was treate...

Embodiment 3

[0031] Example 3: Increasing ADMA increases trophoblast apoptosis

[0032]To further verify the importance of PRMT as a regulator of trophoblast apoptosis, we used its proteolytic product ADMA to corroborate. The decidual macrophages derived from normal pregnant women were sorted and purified by CD14 magnetic beads and cultured in the lower chamber of the Transwell plate, and the HTR-8 / SVneo cells were spread in the upper chamber of the Transwell plate. The decidual macrophages in the lower chamber were divided into two groups. The treatment group was treated with 60 μM exogenous ADMA, and the control group was treated with DMSO, a drug solvent equal to the volume of ADMA. After treatment for 24h, 48h or 72h, the HTR-8 / SVneo cells in the upper chamber were collected, and apoptosis analysis was performed by flow cytometry. The experimental results showed that compared with macrophages in the control group, macrophages treated with ADMA for 48h or 72h were co-cultured with HTR-...

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Abstract

The invention relates to an application of PRMT3 in diagnosis or treatment of spontaneous abortion. By analyzing and comparing the expression level of the PRMT3 in the decidua of normal pregnancy and recurrent abortion (RSA) patients, the phenomenon that the expression level of the PRMT3 is increased in decidua tissues and decidua macrophages of the RSA patients is found; the apoptosis of the trophoblast HTR-8/SVneo can be reduced by inhibiting the PRMT3 in vitro; an in-vivo animal test shows that the PRMT3 inhibitor can reduce the embryo absorption rate of a CBA/J*DBA/2 spontaneous abortion mouse model, so that a new method is provided for clinical diagnosis and treatment of spontaneous abortion.

Description

technical field [0001] The present invention relates to the field of disease diagnosis and treatment, in particular to the application of PRMT3 in the diagnosis or treatment of recurrent spontaneous abortion. Background technique [0002] Recurrent spontaneous abortion (RSA) is an important global health problem with an underappreciated psychological and economic burden on affected couples. RSA is associated with parental chromosomal abnormalities, thrombotic diseases, and structural uterine abnormalities, but the etiology of 50% of RSA is unknown. Therefore, it has important theoretical and clinical significance to clarify the mechanism of RSA and provide corresponding prevention and treatment strategies. Pregnancy is a complex physiological process. During the first trimester, fetal trophoblasts invade the uterine mucosa and remodel the uterine blood vessels. The endometrium becomes decidua through the process of decidualization to maintain embryonic growth and developmen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883G01N33/573A61K45/00A61P15/06A01K67/02
CPCC12Q1/6883G01N33/573A61K45/00A61P15/06A01K67/02C12Q2600/158C12Q2600/136G01N2333/91011G01N2800/36A01K2227/105A01K2267/03
Inventor 金莉萍徐向红郝璠唐林晨
Owner SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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