Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy

Canella, Paula Renata Bueno Campos; Sánchez-Vinces, Salvador; Silva, Álex Aparecido Rosini; Sanches, Pedro Henrique Godoy; Barini, Ricardo; Porcari, Andréia M.; Razolli, Daniela S.; Carvalho, Patrícia de Oliveira

doi:10.1111/aji.13673

Cited by 5 publications

(4 citation statements)

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“…Previous studies have suggested that intralipid can be used as an alternative therapy for patients with RIF ( Coulam, 2021 ), which is accompanied by an altered profile of plasma phospholipids, specifically PC, after treatment ( Canella et al , 2023 ). Through in vitro experiments, it was also confirmed that PC supplementation rescues serotonin-suppressed decidualization.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure

Tian,

Zhang,

Mei

et al. 2024

Human Reproduction Open

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STUDY QUESTION Does abnormal serotonin homeostasis contribute to impaired endometrial decidualization in patients with recurrent implantation failure (RIF)? SUMMARY ANSWER Abnormal serotonin homeostasis in patients with RIF, which is accompanied by decreased monoamine oxidase (MAO) expression, affects the decidualization of endometrial stromal cells and leads to embryo implantation failure. WHAT IS KNOWN ALREADY Previous studies have indicated that the expression of MAO, which metabolizes serotonin, is reduced in the endometrium of patients with RIF, and serotonin can induce disruption of implantation in rats. However, whether abnormal serotonin homeostasis leads to impaired decidualization in patients with RIF and, if so, the mechanism involved, remains unclear. STUDY DESIGN, SIZE, DURATION Endometrial samples from 25 patients with RIF and 25 fertile patients were used to investigate the expression levels of monoamine oxidase A (MAOA), monoamine oxidase B (MAOB) and serotonin. We isolated human endometrial stromal cells to investigate the role of MAOA, MAOB and serotonin in inducing decidualization in vitro and further explored the underlying mechanism using RNA sequencing (RNA-seq) and liquid chromatography-mass spectrometry (LC/MS) analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS The levels of serotonin in the endometrium of patients with RIF were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistofluorescence, and the key genes involved in abnormal serotonin metabolism were analysed via combination with single-cell sequencing data. The effects of MAOA or MAOB on the decidualization of stromal cells were investigated using an in vitro human endometrial stromal cell-induced decidualization model and a mouse artificially induced decidualization model. The potential mechanisms by which MAOA and MAOB regulate decidualization were explored by RNA-seq and LC/MS analysis. MAIN RESULTS AND THE ROLE OF CHANCE We found that women with RIF have abnormal serotonin metabolism in the endometrium and attenuated MAO in endometrial stromal cells. Endometrial decidualization was accompanied by increased MAO in vivo and in vitro. However attenuated MAO caused an increased local serotonin content in the endometrium, impairing stromal cell decidualization. RNA-seq and LC/MS analyses showed that abnormal lipid metabolism, especially phosphatidylcholine metabolism, was involved in the defective decidualization caused by MAO deficiency. Furthermore, decidualization defects were rescued by phosphatidylcholine supplementation. LARGE SCALE DATA RNA-seq information and raw data can be found at NCBI Bioproject number PRJNA892255. LIMITATIONS, REASONS FOR CAUTION This study revealed that impaired serotonin metabolic homeostasis and abnormally reduced MAO expression were among the reasons for RIF. However, the source and other potential functions of serotonin in the endometrium remain to be further explored. WIDER IMPLICATIONS OF THE FINDINGS This study provides new insights into the mechanisms of serotonin homeostasis in human endometrial decidualization and new biomarkers or targets for the treatment of patients with RIF. STUDY FUNDING/COMPETING INTEREST(S) X.Sheng. is supported by grants from the National Natural Science Foundation of China (82001629), the Youth Program of Natural Science Foundation of Jiangsu Province (BK20200116), and Jiangsu Province Postdoctoral Research Funding (2021K277B). H.Sun. is supported by grants from the National Natural Science Foundation of China (82030040). G.Yan. is supported by grants from the National Natural Science Foundation of China (82171653). The authors declare no conflicts of interest.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure

Tian,

Zhang,

Mei

et al. 2024

Human Reproduction Open

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“…Intralipid is an intravenous immunomodulatory agent that works by altering the function of immune cells, especially by lowering the activity of NK cells. NK cells play an important role in the immunoregulation of normal pregnancy, but their abnormally high activity is associated with RSA 108,109 . By reducing the activity of NK cells, Intralipid helps to create a more tolerant immune environment, thereby promoting the survival and development of the embryo.…”

Section: Diagnosis and Treatment Of Rsa With A Focus On Immunitymentioning

confidence: 99%

Maternal‐fetal immunity and recurrent spontaneous abortion

Yao,

Ye,

Chen

et al. 2024

American J Rep Immunol

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Recurrent Spontaneous Abortion (RSA) is a common pregnancy complication, that has multifactorial causes, and currently, 40%–50% of cases remain unexplained, referred to as Unexplained RSA (URSA). Due to the elusive etiology and mechanisms, clinical management is exceedingly challenging. In recent years, with the progress in reproductive immunology, a growing body of evidence suggests a relationship between URSA and maternal‐fetal immunology, offering hope for the development of tailored treatment strategies. This article provides an immunological perspective on the pathogenesis, diagnosis, and treatment of RSA. On one hand, it comprehensively reviews the immunological mechanisms underlying RSA, including abnormalities in maternal‐fetal interface immune tolerance, maternal‐fetal interface immune cell function, gut microbiota‐mediated immune dysregulation, and vaginal microbiota‐mediated immune anomalies. On the other hand, it presents the diagnosis and existing treatment modalities for RSA. This article offers a clear knowledge framework for understanding RSA from an immunological standpoint. In conclusion, while the “layers of the veil” regarding immunological factors in RSA are gradually being unveiled, our current research may only scratch the surface. In terms of immunological etiology, effective diagnostic tools for RSA are currently lacking, and the efficacy and safety of immunotherapies, primarily based on lymphocyte immunotherapy and intravenous immunoglobulin, remain contentious.

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“…Власне, феномен збільшення відсотка CD16позитивних мПК -відносно відомий, і його пов'язують із несприятливим репродуктивним прогнозом. Ще у дослідженнях 90-х років минулого сторіччя зазначалося про збільшення частки CD16 + CD56 dim -клітин та зменшення популяції CD16 -CD56 bright у жінок зі звичним невиношуванням [16,24], з перериванням вагітності після застосування ДРТ [9].…”

Section: результати дослідження та їх обговоренняunclassified

Immunomodulatory effect of granulocyte colony-stimulating factor in repeated implantation failures in embryo transfer programs

Sudoma

Goncharova

Dons’koi

2023

RHW

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The objective: to determine the effectiveness of intrauterine administration of granulocyte colony-stimulating factor depending on endometrium immune phenotype in patients with repeated implantation failures in embryo transfer programs.Material and methods. Endometrial biopsy during the implantation window in an artificial cycle before and (in some patients) after intrauterine administration of granulocyte colony-stimulating factor (G-CSF) was performed in 42 patients with repeated implantation failures and gestational carriers (20 women) as a control group. Flow cytometry was used to count classes and subclasses of endometrial lymphocytes in endometrial tissue samples.Results. The population of endometrial immune cells in patients with repeated implantation failures and fertile women was compared. Pregnancy and live birth rates depending on endometrium immune phenotype in patients with repeated implantation failures after intrauterine administration of granulocyte colony-stimulating factor in embryo transfer program were determined and the effect of intrauterine administration of granulocyte colony-stimulating factor on endometrial immune phenotype was evaluated.High expression of HLA-DR and CD16 on uterine natural killers is reliably associated with successful implantation after intrauterine administration of granulocyte colony-stimulating factor in an embryo transfer program. It was established that in the group with an immature immune endometrial phenotype the frequency of pregnancy (53.8 %) and the frequency of live births (53.8 %) were twice higher compared to the rest of the patients with other variants or the absence of changes in the immune profile (pregnancy rate and frequency live birth rate – 26.9 %).Conclusions. One-third of patients with repeated implantation failures in genetically tested embryos transfer programs have a unique immune status of endometrium characterized by high expression of HLA-DR and CD16 on uterine natural killers. Intrauterine administration of granulocyte colony-stimulating factor leads to decrease of HLA-DR and CD16 expression on uterine natural killers and promotes successful implantation in embryo transfer program in this group of patients.

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Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy

Cited by 5 publications

References 36 publications

Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure

Dysregulation of endometrial stromal serotonin homeostasis leading to abnormal phosphatidylcholine metabolism impairs decidualization in patients with recurrent implantation failure

Maternal‐fetal immunity and recurrent spontaneous abortion

Immunomodulatory effect of granulocyte colony-stimulating factor in repeated implantation failures in embryo transfer programs

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