scholarly journals Temporal Changes In Cyclin D-CDK4/CDK6 And Cyclin E-CDK2 Pathways: Implications For The Mechanism of Deficient Decidualization In An Immune-Based Mouse Model of Unexplained Recurrent Spontaneous Abortion

2021 ◽  
Author(s):  
Zhuo Chang ◽  
Hai-xue Kuang ◽  
Xueming Zhou ◽  
Hui Zhu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Cyclin E ◽  
Underlying Mechanism ◽  
Recurrent Spontaneous Abortion ◽  
Cyclin D ◽  
Decidual Tissue ◽  
Cytokine Levels ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Hematoxylin And Eosin ◽  
Embryo Resorption

Abstract Deficient endometrial decidualization has been associated with unexplained recurrent spontaneous abortion (URSA). However, the underlying mechanism is poorly understood. Here, we aimed to investigate the temporal cytokine changes and the involvement of the cyclin D-cyclin-dependent kinase (CDK)4/CDK6 and cyclin E-CDK2 pathways in the regulation of the G1 phase of the cell cycle during decidualization in a murine model of URSA. Serum and decidual tissues of URSA group and normal pregnant (NP) group mice were collected from gestation day 4 (GD4) to GD8. The embryo resorption and abortion rates were observed on GD8 and the decidual tissue status was assessed using hematoxylin and eosin staining. Cytokine levels in decidual tissues were analyzed using western blotting and reverse transcription polymerase chain reaction. We found that the embryo resorption rate was significantly increased in the URSA group compared to that in the NP group on GD8. The expression of the decidualization marker prolactin in the serum and decidual lysate of the URSA group was significantly decreased on GD6-8 compared to that of the NP group. Cyclin D, CDK4, CDK6, cyclin E, CDK2 and pRb levels in the URSA group mice were significantly lower compared to those in the NP group mice on GD6-8. Our results suggest that the hyperactivated cyclin D-CDK4/CDK6 and cyclin E CDK2 pathways inhibit the decidualization process on GD4, leading to deficient decidualization on GD8. Moreover, they clarify the role of cytokines in the cyclin D-CDK4/6 and cyclin E-CDK2 pathways during decidualization and provide new insight into URSA pathogenesis.

scholarly journals Distinct changes of in BTLA, ICOS, PD-1, and TIGIT expression on peripheral blood and decidual CD8+ T cells in women with unexplained recurrent spontaneous abortion†

2020 ◽  
Vol 103 (5) ◽  
pp. 1012-1017
Author(s):  
Qianqian Liang ◽  
Lingxia Tong ◽  
Liping Xiang ◽  
Sujuan Shen ◽  
Chenhuan Pan ◽  
...  
Keyword(s):  
T Cells ◽  
Spontaneous Abortion ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Immune Escape ◽  
Recurrent Spontaneous Abortion ◽  
Decidual Tissue ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
The Difference

Abstract The two-way communication between the mother and the fetus is accomplished by immune cells. CD8+ T cells of normal pregnant (NP) women express progesterone receptor (PR). Binding of PR to progesterone (P) and the production of progesterone-induced blocking factor (PIBF) can aid immune escape, which is an important factor in the maternal immune response. We detected the proportion of CD8+ T cells and the expression of the surface costimulatory molecules BTLA, TIGIT, ICOS, and PD-1 in peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion (URSA) and in NP women. All patients were at 8 -10 weeks of gestation. The results showed that there was no change in the proportions of CD8+ T cells in peripheral blood and decidual tissues of URSA patients compared to those of NP women. In peripheral blood, compared with the NP group, the URSA group showed decreased expression of BTLA + CD8+ T cells and the difference was statistically significant, but there was no difference between the groups in terms of TIGIT + CD8+, PD-1 + CD8+, and ICOS + CD8+ T cells. There was no change in the levels of TIGIT + CD8+, PD-1 + CD8+, ICOS + CD8+, and BTLA + CD8+ T cells in decidual tissue. These data confirm that the number of CD8+ T cells in peripheral blood and decidual tissue is not the main factor leading to the pathogenesis of URSA, and other immune cells may play an important role in URSA, but this hypothesis needs further exploration and research.

scholarly journals Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao-Hui Wang ◽  
Sha Xu ◽  
Xiang-Yu Zhou ◽  
Rui Zhao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Embryo Implantation ◽  
Underlying Mechanism ◽  
Recurrent Spontaneous Abortion ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Iron Sulfur ◽  
Succinate Dehydrogenase Complex ◽  
Extravillous Trophoblasts ◽  
Control Study

AbstractDysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.

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