The latest medical research on Reproductive Endocrinology & Infertility
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about reproductive endocrinology & infertility gathered by our medical AI research bot.
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Efficacy of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: a systematic review and meta-analysis.American Journal of
we aimed to evalute the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA).
Pubmed, Embase, Web of science, Cochrane library we searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes.
A total of fifteen articles involving 902 patients were included in meta-analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients[OR = 3.06, 95%CI(1.23, 7.64, P = 0.02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = 0.4, 95%CI(-2.47, 3.15, P = 0.81],CD4+[OR = 1.16, 95%CI(-4.60, 6.93, P = 0.69], and decrease the expression of CD8+[OR = -1.78, 95%CI(-5.30, 1.75, P = 0.32], but there is no statistical significance.
IVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high-quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit. This article is protected by copyright. All rights reserved.
Rac1 is involved in uterine myometrium contraction in the inflammation associated preterm birth.Reproduction
Preterm birth (PTB) is a public health issue. The WHO has recommended the use of tocolytic treatment to inhibit preterm labour and improve pregnanc...
The role of Angiotensin II and relaxin in vascular adaptation to pregnancy.Reproduction
During pregnancy, systemic and uteroplacental blood flow increase to ensure an adequate blood supply that carries oxygen and nutrients from the mot...
Natural killer cell profiles in recurrent pregnancy loss: increased expression and positive associations with tactile and lilrb1.American Journal of
NK cells are important for healthy pregnancy and aberrant phenotypes or effector functions have been associated with RPL. We compared expression of a broad panel of NK cell receptors, including immune checkpoint receptors, and investigated their clinical association with RPL as this might improve patient stratification and prediction of RPL.
Peripheral blood mononuclear cells were isolated from fifty-two women with RPL and from twenty-two women with an uncomplicated pregnancy for flowcytometric analysis and plasma was used to determine anti-CMV IgG antibodies.
Between RPL and controls, we observed no difference in frequencies of T-, NKT or NK cells, in CD56dimCD16+ or CD56brightCD16- NK cell subsets or in the expression of KIRs, NKG2A, NKG2C, NKG2D, NKp30, NKp44, NKp46 or DNAM1. NK cells from women with RPL had a higher expression of LILRB1 and TACTILE and this was associated with the number of losses. The immune checkpoint receptors PD1, TIM3 and LAG3 were not expressed on peripheral blood NK cells. In RPL patients, there was a large variation in NKG2C expression and higher levels could be explained by CMV seropositivity.
Our study identified LILRB1 and TACTILE as NK cell receptors associated with RPL. Moreover, we provide first support for the potential role of CMV in RPL via its impact on the NK cell compartment. Thereby our study could guide future studies to confirm the clinical association of LILRB1, TACTILE and NKG2C with RPL in a larger cohort and to explore their functional relevance in reproductive success. This article is protected by copyright. All rights reserved.
Perinatal outcome and long-term infectious hospitalizations of offspring born to women with known drug allergy.American Journal of
We aimed to evaluate perinatal outcomes and long-term infectious hospitalization in the offspring of women with documented drug allergy.
The study was conducted at the Soroka University Medical Center, a tertiary medical center. For perinatal outcomes, generalized estimation equation (GEE) models were used controlling for maternal age, maternal diabetes mellitus, smoking, and hypertensive disorders. The study groups were followed until 18 years of age for infectious-related hospitalizations. A Kaplan-Meier survival-curve was used to compare cumulative incidence of long-term infectious hospitalizations. A Cox proportional hazards model was conducted to control for confounders.
During the study period, 243,682 deliveries met the inclusion criteria, of which 9,756 (4.0%) occurred in women with documented drug allergy. Using GEE, maternal drug allergy was found to be a significant independent risk factor for hypertensive disorders, diabetes mellitus, intra-uterine growth restriction (IUGR) and preterm delivery. Offspring also had significantly higher rates of long-term infectious hospitalizations. Kaplan-Meier survival-curves demonstrated significantly higher cumulative incidence rates of infectious hospitalization (log rank p<0. 001). In a Cox proportional hazards model, being born to a mother with documented a drug allergy was independently associated with infectious hospitalization of the offspring in the long-term.
Maternal documented drug allergy is independently associated with adverse perinatal outcome such as IUGR and preterm delivery and increased risk of long- term infectious hospitalization of the offspring. This article is protected by copyright. All rights reserved.
Macrophage Polarization in Placenta Accreta and Macrophage-trophoblast Interactions.American Journal of
Placenta accreta (PA) is defined by an abnormal invasion of placental trophoblasts into the myometrium, which can lead to serious postpartum complications. Macrophages play an important role in the regulation of trophoblast function. Both granulocyte colony-stimulating factor (G-CSF) and its receptor (granulocyte colony-stimulating factor receptor, G-CSFR) have effects on trophoblast invasion. However, the current understanding of G-CSF secretion, G-CSFR expression, abnormal polarization of decidual macrophages (dMϕ) in PA and the abnormal invasion of placental trophoblasts into the myometrium are limited.
The polarization of dMϕ in PA was analyzed by flow cytometry (FCM), and the expression of G-CSFR in placental trophoblasts in PA was evaluated by immunohistochemistry. In an in vitro co-culture model, we investigated the effects of HTR-8/SVneo trophoblasts cell line (HTR-8) on macrophage human monocyte cell line (THP-1) polarization and G-CSF secretion, and we also analyzed the effects of THP-1 cells, especially M2-like subtype, on primary trophoblasts and HTR-8 proliferation, invasion, and adhesion. FCM, transwell assays, adhesion assays, and proliferation assays were used in the above model.
Compared with controls (n = 9), dMϕ showed significantly lower levels of M1 markers CD80 and CD86 and higher levels of the M2 markers CD163 and CD206, and G-CSFR expression of placental trophoblasts was increased in PA(n = 5). In vitro experiments showed that the trophoblast HTR-8 cell line induced polarization of THP-1 cells to an M2-like subtype and increased their secretion of G-CSF. Furthermore, IL-4/IL-13-induced M2-like THP-1 macrophages were able to increase the expression of G-CSFR, proliferation, invasion and adhesion of both primary trophoblasts and HTR-8 trophoblasts.
There is an altered immune imbalance at the maternal-fetal interface in PA, which further may lead to abnormal trophoblast function. G-CSF and its receptors may play important roles in abnormal polarization of macrophages and abnormal invasion of trophoblasts. This article is protected by copyright. All rights reserved.
Isolation and characterization of uterine leukocytes collected from uterine swab technique.American Journal of
Leukocytes from the maternal-fetal interface are a valuable tool to study local changes in immune function during pregnancy; however, sampling can be challenging due to inadequate tissue availability and the invasive nature of placental bed biopsy. Here, we aim to purify and characterize leukocytes from paired peripheral and uterine blood samples to assess whether a less invasive method of uterine blood collection could yield a population of enriched uterine leukocytes suitable for ex vivo and in vitro analyses.
Human peripheral blood mononuclear cells (PBMC) and uterine blood (expressed from surgical gauze post C-section) mononuclear cells (UBMC) were isolated, and immunophenotypic information was acquired by multi-parameter flow cytometry. PBMC and UBMC were stained for markers used to define T and B lymphocytes, macrophages, regulatory T (TReg ) cells, and natural killer (NK) cells. Prime flow was performed to check expression and analysis of CD16- CD56++ and CD16- CD56++ NK transcript in PBMC and UBMC samples.
Immunophenotyping revealed that over 95% of both live PBMC and UBMC consisted of CD45+ leukocytes. Higher percentages of CD16- CD56++ , characterized as uterine NK (uNK) cells, were observed in UBMC samples as compared to PBMC samples (18.41% of CD45+ CD3- vs. 2.73%, respectively), suggesting that CD16- CD56++ cells were enriched in these samples. In UBMC, 49.64% of CD3-negative cells were of peripheral NK phenotype (CD16+ CD56++ ), suggesting infiltration of maternal peripheral NK (pNK) cell in the uterine interface.
Intrauterine leukocytes, especially CD16- CD56++ NK cells, can be collected in sufficient numbers with increased purity by sampling the uterine cavity postdelivery with surgical gauze. Our results suggest that this non-invasive protocol is a useful sampling technique for isolating CD16- CD56++ cells, however, due to peripheral blood contamination, the NK cell yield could be lower compared to actual decidual or endometrial samples post-partum which is more invasive. This article is protected by copyright. All rights reserved.
Comparative proteome profiling of seminal components reveal impaired immune cell signaling as paternal contributors in recurrent pregnancy loss patients.American Journal of
Recurrent Pregnancy Loss (RPL) is usually evaluated from a women's perspective, however, recent evidence implies involvement of male factors as paternally expressed genes predominate placenta. During fertilization, prior to implantation the immune system purposefully produces early pregnancy factors with potent immunomodulatory properties for adaptation to antigenically dissimilar embryo. Therefore, it is hypothesized that paternal immunological factors play a role in RPL.
Comparative proteome profiling (label free liquid chromatography mass spectroscopy: LC-MS/MS) of the seminal extracellular vesicles (SEVs), extracellular vesicle free seminal plasma (EVF-SP) and spermatozoa was carried out in semen of RPL patients (n = 21) and fertile donors (n = 21). This was followed by pathway and protein-protein interaction analysis, and validation of key proteins expression (western blot).
A total of 68, 28 and 49 differentially expressed proteins in SEVs, EVF-SP and spermatozoa of RPL patients, respectively were found to be involved in inflammatory response, immune cell signaling and apoptosis were detected. In SEVs, underexpressed GDF15 and overexpressed C3 imply distorted maternal immune response to paternal antigens leading to impaired decidualization. Dysregulated TGFβ signaling in EVF-SP surmises defective modulation of inflammatory response and induction of immune tolerance to seminal antigens in the female reproductive tract through generation of regulatory T cells. Retained histone variants in spermatozoa construe defective expression of early paternal genes while underexpressed PTN may inflict defective angiogenesis resulting in expulsion of decidua.
Impaired modulation of immune response and improper placental development due to altered cytokine levels in seminal components may be the contributing paternal factors in RPL. This article is protected by copyright. All rights reserved.
Pregnancy Imparts Distinct Systemic Adaptive Immune Function.American Journal of
Pregnancy represents a state of systemic immune activation that is primarily driven by alterations in circulating innate immune cells. Recent studies have suggested that cellular adaptive immune components, T cells and B cells, also undergo changes throughout gestation. However, the phenotypes and functions of such adaptive immune cells are poorly understood. Herein, we utilized high-dimensional flow cytometry and functional assays to characterize T-cell and B-cell responses in pregnant and non-pregnant women.
PBMCs from pregnant (n = 20) and non-pregnant (n = 25) women were used for phenotyping of T-cell and B-cell subsets. T-cell proliferation and B-cell activation were assessed by flow cytometry after stimulation, and lymphocyte cytotoxicity was evaluated using a cell-based assay. Statistical comparisons were performed using linear mixed effects models.
Pregnancy was associated with modestly enhanced basal activation of peripheral CD4+ T cells. Both CD4+ and CD8+ T cells from pregnant women showed increased activation-induced proliferation; yet, a reduced proportion of these cells expressed activation markers compared to non-pregnant women. There were no differences in peripheral lymphocyte cytotoxicity between study groups. A greater proportion of B cells from pregnant women displayed memory-like and activated phenotypes, and such cells exhibited higher activation following stimulation.
Maternal circulating T cells and B cells display distinct responses during pregnancy. The former may reflect the unique capacity of T cells to respond to potential threats without undergoing aberrant activation, thereby preventing systemic inflammatory responses that can lead to adverse perinatal consequences. This article is protected by copyright. All rights reserved.
Age associated changes in miRNA profile of bovine follicular fluid.Reproduction
We examined age-associated changes in microRNA (miRNA) profiles in the follicular fluid (FF) of cows. The role of miR-19b, which is abundant in the...
Inflammasome activation in preeclampsia and intrauterine growth restriction.American Journal of
Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8%-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR.
In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery.
NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples versus NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood.
NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR.
Circ_0077109 sponges miR-139-5p and upregulates HOXD10 in trophoblast cells as potential mechanism for preeclampsia progression.American Journal of
One of the important reasons for the development of preeclampsia (PE) is the abnormal function of trophoblast cells. Many circular RNAs (circRNAs) have been confirmed to participate in the regulation of trophoblast cell function to mediate PE progression. However, whether circ_0077109 is involved in PE progression through regulating trophoblast cell function remains unclear.
Quantitative real-time PCR was utilized for measuring the expression of circ_0077109, microRNA (miR)-139-5p and homeobox D10 (HOXD10). Trophoblast cell proliferation, apoptosis, invasion, and angiogenesis was assessed cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and tube formation assay. In addition, western blot analysis was used to determine protein expression. The interaction between miR-139-5p and circ_0077109 or HOXD10 was verified by dual-luciferase reporter assay and RIP assay.
Our results pointed out that circ_0077109 was a circRNA with upregulated expression in PE patients. Overexpression of circ_0077109 suppressed trophoblast cell proliferation, invasion, and angiogenesis, while increased apoptosis. MiR-139-5p was found to be sponged by circ_0077109, and its mimic reversed the suppressive effect of circ_0077109 on trophoblast cell function. HOXD10 was a target of miR-139-5p, and its overexpression inhibited trophoblast cell proliferation, invasion, and angiogenesis. MiR-139-5p inhibitor could repress trophoblast cell function, while this effect could be reversed by HOXD10 knockdown.
In summary, we confirmed that circ_0077109 inhibited trophoblast cell function through the regulation of miR-139-5p/HOXD10 axis, which might be a potential target for PE treatment. This article is protected by copyright. All rights reserved.