scholarly journals An Imbalance of IL-33/ST2-AXL-Efferocytosis Axis Induces Pregnancy Loss Through Metabolic Reprogramming of Decidual Macrophage

Author(s):  
Yan-Ran Sheng ◽  
Wen-Ting Hu ◽  
Hui-Hui Shen ◽  
Chun-Yan Wei ◽  
Yu-Kai Liu ◽  
...  

Abstract During the implantation of embryo, apoptosis is inevitable. These apoptotic cells (AC) are removed by efferocytosis, which fills the macrophage with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the interrelationship between efferocytosis metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here we report a positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum level of IL-33, sST2, along with IL-33, ST2, efferocytosis and metabolism of dMΦs from both normal gravidas and unexplained recurrent pregnancy loss (RPL) patients. And we revealed the disturbance of IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from the patients with RPL. Afterwards the dMΦs swallowing so many apoptotic cells secreted more sST2 and less TGF-β, which polarized dMΦs towards M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis metabolism of RPL dMΦs towards oxidative phosphorylation and exacerbated the disruption of IL-33/ST2 signaling pathway. The metabolic disorders also led to the dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and the secondary necrosis occurred. We also screened efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. And the IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation of mouse IL-33 could partially alleviate the fate of embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for the homeostasis of microenvironment at the maternal-fetal interface.

2021 ◽  
Vol 84 (1) ◽  
pp. 2361-2365
Author(s):  
Abdelhaseib salah Saad ◽  
Zakaria Fouad Sanad ◽  
Ahmed Hammouda Hossameldin ◽  
Dalia Ibrahim

Author(s):  
Sidra Asad Ali ◽  
Bushra Moiz ◽  
Lumaan Sheikh

Abstract Objective: To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes. Method: The prospective study was conducted at the Aga Khan University Hospital, Karachi, from January 1 to December 31, 2016, and comprised females ?40 years having history of two or more foetal losses with no apparent aetiology. Restriction fragment length polymorphism- Polymerase chain reaction was performed using MnlI and HindIII restriction enzymes for factor V Leiden G1691A and prothrombin gene mutation G20210A. Females with two or more consecutive normal pregnancies were enrolled as the control group. Data was analysed using SPSS 19. Results: Of the 172 participants with a mean age of 29.3±5.9 years (range: 19-38 years). 86(50%) each were healthy controls and those with recurrent pregnancy loss. There were 238 livebirths among the controls compared to 13 in the other group. Factor V Leiden G1691A was identified in 2(2.3%) women, and prothrombin gene mutation G20210A in 1(1.2%) woman in the patient group, while no mutation was identified in the control group. Conclusion: The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low. Continuous....


2018 ◽  
Vol 46 (7) ◽  
pp. 764-770 ◽  
Author(s):  
Maor Kabessa ◽  
Avi Harlev ◽  
Michael Friger ◽  
Ruslan Sergienko ◽  
Baila Litwak ◽  
...  

Abstract Background: Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies. Three to four percent of the couples with RPL have chromosomal aberrations (CA) in at least one partner. The parent’s structural chromosomal abnormalities may cause an unbalanced karyotype in the conceptus which could lead to implantation failure, early or late pregnancy loss, or delivery of a child with severe physical and/or mental disabilities. Objective: To compare live birth rates of couples with CA to couples with normal karyotypes and to investigate medical and obstetric characteristics and pregnancy outcomes of couples with CA and RPL who attend an RPL clinic at a tertiary hospital. Methods: A retrospective cohort study, including 349 patients with two or more consecutive pregnancy losses. The study group consisted of 52 patients with CA, and the control group consisted of 297 couples with normal karyotype. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center and had at least one subsequent spontaneous pregnancy. Results: The demographic and clinical characteristics were not found to be statistically different between the two groups. The group of carriers of CA had 28/52 (53.8%) live births in their index pregnancy vs. the normal 202/297 (68%) (P=0.067, CI 95%) in the control group. No statistically significant etiology was found between the study group and the control group. A statistically significant difference in live birth rates was found when comparing the total amount of pregnancies [index pregnancy (IP)+post index pregnancy (PIP)] between the study group and the control group (54.16% vs. 67.82%, respectively, P=0.0328). Conclusion: Patients with RPL and CA who have spontaneous pregnancies, have a good prognosis (63.4%) of a successful pregnancy with at least one of the pregnancies (index or post index) resulting in a live birth.


Sign in / Sign up

Export Citation Format

Share Document