Effects of cyclosporine A on proliferation, invasion and migration of HTR-8/SVneo human extravillous trophoblasts

Huang, Wei; Lu, Weiying; Li, Qi; Xie, Baoguo; Luo, Sheng; Wei, Yunjian; Ma, Yanlin; Huang, Yuanhua

doi:10.1016/j.bbrc.2020.09.072

Cited by 16 publications

(10 citation statements)

References 31 publications

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“…CsA can pass through the placenta, where it inhibits the maternal rejection of embryos and promotes the proliferation, invasion, and migration of villous trophoblast cells by inducing the expression of proteins that regulate the function of HTR8/SVneo cells, thereby improving the embryo implantation rates. 28 The evidence on the limited published data suggests a demonstrable clinical benefit of CsA for patients with URSA. However, studies on the therapeutic effect of URSA in pregnant women have been small and nonrandomized.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

Wang¹,

Ge²,

Zhou³

2021

IJWH

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Background The World Health Organization (WHO) has defined Unexplained Recurrent Spontaneous Abortion (URSA) as three and more consecutive miscarriages before the 20th week of gestation. To date, empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Studies have shown that URSAs are associated with Th1/Th2 and Th17/Treg immune imbalances at the maternal-fetal interface. The immunosuppressant cyclosporine A (CsA) is widely used in patients with organ transplantation or autoimmune diseases, and it has a good safety profile in pregnant women. However, high-quality evidence for CsA treatment of URSAs is lacking. Our purpose with this study is to evaluate the efficacy and safety of CsA for improving pregnancy outcomes in patients with URSAs and to explore the role of CsA in regulating the immune balance. Methods/Design We expect to officially initiate our study at the Taizhou People’s Hospital in March 2022. We defined the live birth rate as the primary outcome, and the secondary outcomes include the rates of successful pregnancy, miscarriage, pregnancy complications, and adverse pregnancy outcomes, and newborn birth weights. Patients who meet URSA eligibility criteria will be randomized in a 1:1 ratio into either a study group receiving CsA 2 weeks after fertilization or a control group receiving placebo at 2 weeks after fertilization (the women in both groups will receive the relevant treatment for 6 months). In addition, we will collect peripheral blood samples of the participants before and after the treatments, and we will isolate mononuclear cells and measure cytokine levels (IFN-γ, TNF-α, IL-2, IL-10, IL-6, IL-4) and Th1/Th2, Th17/Treg ratios. Discussion This is the first randomized controlled trial to evaluate the clinical and immunomodulatory effects of CsA on the pregnancy outcomes of women with URSA and our results will provide evidence to evaluate the use of CsA as a treatment for women with URSAs.

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Section: Discussionmentioning

confidence: 99%

Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

Wang¹,

Ge²,

Zhou³

2021

IJWH

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“…considered CsA reduced the proportion of Th17 cells and promoted Treg cells dominance in pregnant females with a history of recurrent spontaneous abortion (RSA). Previous animal investigation and in vitro experiments showed the positive role of CsA in improving the biological functions of trophoblast cells and inducing maternal‐fetal tolerance in spontaneous abortion with the mechanism of decreased costimulatory molecules or increased coinhibitory molecules and rectified balance of Th1/Th2 or Th17/Treg ratios 24–26 . In vitro studies confirmed a favorable modulatory effect of CsA on trophoblast function during the first pregnancy trimester 27–30 .…”

Section: Discussionmentioning

confidence: 79%

“…22 Wang et al 23 animal investigation and in vitro experiments showed the positive role of CsA in improving the biological functions of trophoblast cells and inducing maternal-fetal tolerance in spontaneous abortion with the mechanism of decreased costimulatory molecules or increased coinhibitory molecules and rectified balance of Th1/Th2 or Th17/Treg ratios. [24][25][26] In vitro studies confirmed a favorable modulatory effect of CsA on trophoblast function during the first pregnancy trimester. [27][28][29][30] Other research suggested that abortion-prone matings mice could benefit from CsA on pregnancy outcomes by inducing maternal-fetal immune tolerance.…”

Section: Logistic Regression Analysismentioning

confidence: 99%

Improved pregnancy outcomes of cyclosporine A on patients with unexplained repeated implantation failure in IVF/ICSI cycles: A retrospective cohort study

Cheng

et al. 2022

American J Rep Immunol

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Problem: Repeated implantation failure (RIF) is a daunting obstacle restricting the further improvement of embryo implantation rate (IR) and live birth rate (LBR). The beneficial effect of cyclosporine A (CsA) on reproductive outcomes of unexplained RIF(URIF) was explored after de novo embryo transfer (ET). Method of study:A retrospective cohort study was conducted, comparing pregnancy outcomes of 146 cycles (CsA group, n = 62; control group, n = 84) at the IVF center of

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“…Meanwhile, studies have found that lowdose CsA can promote the proliferation, invasion, and migration of trophoblast cells in early pregnancy by activating the MAPK signaling pathway. 33,34 In addition, animal studies have also confirmed that low-dose CsA can improve the pregnancy outcomes of abortive model mice by promoting the proliferation and invasion of trophoblast cells in mice and inducing immune tolerance. 35 Studies have also Prednisolone is a type of glucocorticoid that can inhibit the generation and release of histamine and other inflammatory mediators and has a strong immunosuppressive effect.…”

Section: Discussionmentioning

confidence: 95%

“…In recent years, many studies have found that CsA has a bidirectional regulatory effect on the maternal–fetal interface. Meanwhile, studies have found that low‐dose CsA can promote the proliferation, invasion, and migration of trophoblast cells in early pregnancy by activating the MAPK signaling pathway 33,34 . In addition, animal studies have also confirmed that low‐dose CsA can improve the pregnancy outcomes of abortive model mice by promoting the proliferation and invasion of trophoblast cells in mice and inducing immune tolerance 35 .…”

Section: Discussionmentioning

confidence: 98%

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

Qin

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective: Reports said immunotherapy is effective for the treatment of idiopathic recurrent miscarriage (RM). Immunotherapy is invasive, and lymphocyte therapy carries some risk of infection. Oral immunosuppressants have the advantages of simple administration and convenience; however, there is no statistical analysis of whether they can improve pregnancy outcomes in patients with idiopathic RM.Methods: Six databases were searched for studies on oral immunosuppressants and RM; 374 articles were identified. There were two oral immunosuppressants, cyclosporine A and prednisone; two studies were on cyclosporine A and three studies were on prednisone for RM.Results and discussion: In total, 554 RM patients were included in this analysis, including 357 patients who received oral immunosuppressive agents and 197 patients who received basic treatment, placebo, or no treatment. Oral administration of cyclosporine A or prednisolone increases live birth rate (OR = 3.6, 95% CI: 2.1-6.15, p < 0.00001) and ongoing pregnancy rate (OR = 8.82, 95% CI: 2.91-26.75, p = 0.0001) in patients with idiopathic RM. Drug use reduced miscarriage rate (OR = 0.21, 95% CI: 0.08-0.52, p = 0.0007); however, there was significant heterogeneity (I 2 = 73%) and a moderate-to-severe risk of bias. There was no effect on premature birth rate (OR = 2.26, 95% CI: 0.96-5.31, p = 0.06). This meta-analysis cannot provide a reference for the duration of medication treatment because the selected studies had inconsistent durations. What is new and conclusion:We did a statistical analysis and found that oral immunosuppressants (including cyclosporine A or prednisolone) can improve pregnancy outcomes in patients with idiopathic RM, increase live birth rate and ongoing pregnancy rate, and reduce miscarriage rate.

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Effects of cyclosporine A on proliferation, invasion and migration of HTR-8/SVneo human extravillous trophoblasts

Cited by 16 publications

References 31 publications

Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

Improved pregnancy outcomes of cyclosporine A on patients with unexplained repeated implantation failure in IVF/ICSI cycles: A retrospective cohort study

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

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