Aberrant Placental Villus Expression of miR-486-3p and miR-3074-5p in Recurrent Miscarriage Patients and Uterine Expression of These MicroRNAs during Early Pregnancy in Mice

2015 ◽  
Vol 81 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Yan Gu ◽  
Xuan Zhang ◽  
Qian Yang ◽  
Jianmei Wang ◽  
Yaping He ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
Placental Villus

MNSFβ Promotes the Proliferation and Migration of Human Extravillous Trophoblast Cells and the Villus Expression Level of MNSFβ Is Decreased in Recurrent Miscarriage Patients

2020 ◽  
Vol 86 (1-2) ◽  
pp. 27-39
Author(s):  
Nan Wang ◽  
Qian Yang ◽  
Yan Gu ◽  
Xingxing Zhen ◽  
Yan Shi ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
First Trimester ◽  
Expression Level ◽  
Extravillous Trophoblast ◽  
Placental Villus ◽  
Expression Levels ◽  
Placental Villi ◽  
And Migration ◽  
Proliferation And Migration

<b><i>Aims:</i></b> The invasion of extravillous trophoblast (EVT) cells into maternal decidua is essential for the establishment and maintenance of pregnancy. Derangement of EVT cell invasion might cause pregnancy complications including recurrent miscarriage (RM). We previously reported that deficiency of monoclonal nonspecific suppressor factor beta (MNSFβ) led to the early pregnancy failure in mice and the decidual MNSFβ expression level in RM patients was significantly decreased, but the underlying molecular mechanism of the role that MNSFβ played at the maternal-fetal interface remains unclear. Thus, in the present study, we determined effects of downregulated MNSFβ expression on human EVT cell activities. <b><i>Methods:</i></b> The MNSFβ expression in first-trimester human decidual and placental villus tissues was detected, respectively, by immunofluorescence or immunohistochemical analyses. The MNSFβ expression level in the immortalized first-trimester human EVT cell line HTR8/SVneo was downregulated by transfecting the small interfering RNA against MNSFβ and upregulated by transfecting the recombinant pDsRed-MNSFβ plasmids. The proliferation, migration, invasion, and apoptosis activities of HTR8/SVneo cells were, respectively, determined by cytometry assay, scratch test, transwell assay, and FITC/PI staining. The expression levels of P53, RhoA, Bcl-2, Bax, and MMP-9 in HTR8/SVneo cells, as well as the expression levels of MNSFβ and RhoA in placental villi of RM patients and physically normal pregnant women (NP), were examined by Western blot analysis. <b><i>Results:</i></b> MNSFβ protein signals were observed in first-trimester human villus and extravillous trophoblast cells. The downregulated MNSFβ expression significantly attenuated the proliferation, migration, and invasion abilities of HTR8/SVneo cells, accompanied with the obviously decreased expression levels of P53, RhoA, Bcl-2, Bax, and MMP-9, whereas the upregulated MNSFβ expression in HTR8/SVneo cells represented the inverse effects. Furthermore, expression levels of MNSFβ and RhoA in first-trimester human placental villus tissues of RM patients were significantly decreased compared to that of NP women. <b><i>Conclusion:</i></b> These data suggested that MNSFβ promotes proliferation and migration of human EVT cells, probably via the P53 signaling pathway, and the deficiency of MNSFβ in placental villi might lead to early pregnancy loss by reducing proliferation and invasion activities of EVTs.

scholarly journals Menstrual flow as a non-invasive source of endometrial organoids

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tereza Cindrova-Davies ◽  
Xiaohui Zhao ◽  
Kay Elder ◽  
Carolyn J. P. Jones ◽  
Ashley Moffett ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
Milk Proteins ◽  
Receptor Expression ◽  
In Vitro Fertilisation ◽  
Non Invasive ◽  
Menstrual Flow ◽  
Pregnancy Hormones

AbstractAssessment of the endometrium often necessitates a biopsy, which currently involves an invasive, transcervical procedure. Here, we present an alternative technique based on deriving organoids from menstrual flow. We demonstrate that organoids can be derived from gland fragments recovered from menstrual flow. To confirm they faithfully reflect the in vivo state we compared organoids derived from paired scratch biopsies and ensuing menstrual flow from patients undergoing in vitro fertilisation (IVF). We demonstrate that the two sets of organoids share the same transcriptome signature, derivation efficiency and proliferation rate. Furthermore, they respond similarly to sex steroids and early-pregnancy hormones, with changes in morphology, receptor expression, and production of ‘uterine milk’ proteins that mimic those during the late-secretory phase and early pregnancy. This technique has wide-ranging impact for non-invasive investigation and personalised approaches to treatment of common gynaecological conditions, such as endometriosis, and reproductive disorders, including failed implantation after IVF and recurrent miscarriage.

P–426 Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: An Updated Systematic Review and Meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E V Woon ◽  
O Greer ◽  
N Shah ◽  
V Male ◽  
M Johnson
Keyword(s):  
Systematic Review ◽  
Nk Cells ◽  
Early Pregnancy ◽  
Subgroup Analysis ◽  
Recurrent Miscarriage ◽  
Meta Analysis ◽  
Implantation Failure ◽  
Significant Difference ◽  
Uterine Nk Cells ◽  
Definition Of

Abstract Study question Do women with recurrent miscarriage (RM) or implantation failure (RIF) have different levels of uterine Natural Killer (NK) cells compared to fertile controls? Summary answer Women with RIF but not RM are associated with significantly higher levels of CD56+ uterine NK cells compared to controls. What is known already Uterine NK cells (uNK) are different from peripheral NK cells (pNK) and are important in early pregnancy for development of the placenta. The association between uNK and RM/RIF is less clear, but dysfunction of uNK is believed to result in early pregnancy failure. Previous systematic reviews by Seshadri (2014) and Tang (2013) on infertile and RM patients showed no significant difference in uNK levels and highlighted need for further studies. Since, many prospective studies have been published and therefore warrant an updated systematic review. On the other hand, evidence for correlation between uNK and pNK is sparse and needs clarification. Study design, size, duration We have conducted a systematic review and meta-analysis to evaluate three outcomes. The primary outcome was the difference of uNK level in RM/RIF compared to controls. The secondary outcome was livebirth rate in women with RM/RIF with high compared to normal uNK level, and the tertiary outcome was correlation between uNK and pNK in RM/RIF. Participants/materials, setting, methods The electronic database search included MEDLINE, EMBASE, Web of Science and bibliographies from included articles from inception to December 2020 using a combination of MESH and keywords. Search, screen, and data extraction were performed by two reviewers independently. Quality assessment was conducted with ROBINS-I and meta-analysis with Revman 5.3. Out of 4636 studies screened, 43 studies (2539 women) and 3 studies each (598 and 77 women) were analysed for primary, secondary and tertiary outcomes respectively. Main results and the role of chance Our meta-analysis showed that CD56+ uNK were significantly higher in women with RIF but not RM compared to controls (SMD 0.60; 95% CI 0.12–1.08]. Subgroup analysis in RM patients showed no significant difference whether definition of 2 or 3 previous RM was used, in primary/secondary RM compared to controls, or in primary versus secondary RM. CD56+ uNK were significantly higher in RM/RIF when sampled during mid-luteal phase [SMD 0.56; 95% CI 0.19–0.93] but not in the early pregnancy decidua. Interestingly, there was significant difference in CD56+ uNK when analysed by immunohistochemistry [SMD 0.50; CI 0.05–0.94] but not by flow cytometry, and when CD56+ uNK were reported as percentage over total endometrial cells [SMD 0.58; 95% CI 0.10–1.07]. Further subgroup analysis showed significant difference in CD16 + [SMD 0.54; 95% CI 0.18–0.89] but not in CD56+CD16-, CD56+CD16+ or CD57. For pregnancy outcome, there was no significant difference in livebirth rate in RM/RIF patients with high uNK compared to normal uNK [RR 1.06, 95% CI 0.86–1.30]. Mean uNK level in RM patients with subsequent miscarriage was not significantly higher than subsequent livebirth. Finally, the pooled correlation between CD56 pNK and CD56 uNK (r = 0.42; 95% CI –0.04–0.73] was not significant in RM/RIF patients. Limitations, reasons for caution The meta-analysis is limited by quality of some of the studies. Some data were presented in median that was transformed to mean which may result in data skew. Other confounding factors e.g. maternal age, fetal karyotype, number of previous miscarriages and variable definition of controls may contribute to bias. Wider implications of the findings: Clinical interpretation of uNK level needs to be treated with caution because there is significant heterogeneity in method of analysis. There may be a role for uNK measurement in RIF patients however further studies to understand pathophysiology underlying elevated uNK is warranted before recommending it as a diagnostic tool. Trial registration number N/A

scholarly journals Prokineticin receptor variants (PKR1-I379V and PKR2-V331M) are protective genotypes in human early pregnancy

Reproduction ◽  
2013 ◽  
Vol 146 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Mei-Tsz Su ◽  
Sheng-Hsiang Lin ◽  
Yi-Chi Chen ◽  
Li-Wha Wu ◽  
Pao-Lin Kuo
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Intracellular Calcium ◽  
Early Pregnancy ◽  
Calcium Influx ◽  
Recurrent Miscarriage ◽  
Endocrine Gland ◽  
Genotype Frequencies ◽  
Cell Invasiveness ◽  
Cell Cell

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor genes (PROKR1(PKR1) andPROKR2(PKR2)) play an important role in human early pregnancy. We have previously shown thatPROKR1andPROKR2are associated with recurrent miscarriage (RM) using the tag-SNP method. In this study, we aimed to identifyPROKR1andPROKR2variants in idiopathic RM patients by genotyping of the entire coding regions. Peripheral blood DNA samples of 100 RM women and 100 controls were subjected to sequence the entire exons ofPROKR1andPROKR2. Significant non-synonymous variant genotypes present in the original 200 samples were further confirmed in the extended samples of 144 RM patients and 153 controls. Genetic variants that were over- or under-represented in the patients were ectopically expressed in HEK293 and JAR cells to investigate their effects on intracellular calcium influx, cell proliferation, cell invasion, cell–cell adhesion, and tube organization. We found that the allele and genotype frequencies ofPROKR1(I379V) andPROKR2(V331M) were significantly increased in the normal control groups compared with idiopathic RM women (P<0.05).PROKR1(I379V) andPROKR2(V331M) decreased intracellular calcium influx but increased cell invasiveness (P<0.05), whereas cell proliferation, cell–cell adhesion, and tube organization were not significantly affected. In conclusion,PROKR1(I379V) andPROKR2(V331M) variants conferred lower risk for RM and may play protective roles in early pregnancy by altering calcium signaling and facilitating cell invasiveness.

The Euro-Team Early Pregnancy (ETEP) protocol for recurrent miscarriage

1995 ◽  
Vol 10 (6) ◽  
pp. 1516-1520 ◽  
Author(s):  
C.W. Berry ◽  
B. Brambati ◽  
T.K.A.B. Eskes ◽  
N. Exalto ◽  
H. Fox ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage

MATERNAL IMMUNE RESPONSES TO THE FETUS IN EARLY PREGNANCY AND RECURRENT MISCARRIAGE

The Lancet ◽  
1988 ◽  
Vol 332 (8620) ◽  
pp. 1099-1104 ◽  
Author(s):  
I.L. Sargent ◽  
T. Wilkins ◽  
C.W.G. Redman
Keyword(s):  
Immune Responses ◽  
Early Pregnancy ◽  
Recurrent Miscarriage

scholarly journals Meta-analysis and randomized controlled studies: what clinicists should know to prevent regular and spontaneous miscarriages of unexplained genesis?

2021 ◽  
pp. 39-44
Author(s):  
Paul Piette
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
Meta Analysis ◽  
First Trimester ◽  
Recommended Treatment ◽  
Randomized Controlled Studies ◽  
History Of ◽  
Threatened Abortion ◽  
The Moment ◽  
Micronized Progesterone

The etiopathology of recurrent miscarriage is a combination of various factors, including chromosomal defects, genetic or structural abnormalities, endocrine abnormalities, infections, immune dysfunction, thrombophilia disorders, antiphospholipid syndrome, and unexplained causes.It has long been known that progesterone is needed to maintain pregnancy and its physiological development. Insufficient progesterone secretion and its low level in the blood serum in early pregnancy is associated with the threat of miscarriage and loss of pregnancy at a later stage – up to 16 weeks of gestation. The effectiveness of the vaginal micronized progesterone (VMP) at a dose of 400 mg twice a day in the first trimester of pregnancy was evaluated in two recent large high-quality multicenter placebo-controlled studies, one of which included pregnant women with recurrent miscarriages of unexplained origin (PROMISE Trial), and the other study included women with early pregnancy loss (PRISM Trial). A key finding, pioneered in the PROMISE study and later confirmed in the PRISM study, was that VMP treatment associated with an increase in live births in line with the number of previous miscarriages. It has been shown that there is no evidence regarding safety concerns with natural micronized progesterone. Treatment with an VMP should be recommended for women with bleeding in early pregnancy and a history of one or more miscarriages. The recommended treatment regimen is 400 mg 2 times a day (800 mg/day) intravaginal, starting from the moment bleeding is detected up to 16 weeks of pregnancy.In the future, there remains uncertainty effectiveness and safety of alternative progestogens (dydrogesterone) for the treatment of women at high risk of threatened abortion and recurrent miscarriage. It is important that dydrogesterone is a synthetic progestin, its structure is significantly different from natural progesterone, and therefore it is necessary to unequivocally prove the short- and long-term safety of this drug before considering its use in clinical practice.

Miscarriage and recurrent miscarriage

2020 ◽  
pp. 477-488
Author(s):  
Vikram Sinai Talaulikar ◽  
Mushi Matjila
Keyword(s):  
Early Pregnancy ◽  
Pregnancy Loss ◽  
Recurrent Miscarriage ◽  
Significant Proportion ◽  
Phenotypic Characterization ◽  
Future Research ◽  
Management Options ◽  
Global Consensus ◽  
Comprehensive Information ◽  
Definition Of

Complications of early pregnancy, including pregnancy loss and threatened miscarriage, are common. Miscarriage affects almost one in five pregnancies and accounts for utilization of a significant proportion of healthcare resources. Women presenting with miscarriage should ideally be assessed, diagnosed, and managed in early pregnancy assessment units. They should be provided with comprehensive information about expectant, medical, and surgical management options, and helped to make informed decisions about their care. Early pregnancy loss can be a source of considerable distress to women and they should be provided with appropriate support and counselling. Recurrent miscarriage (RM) remains a challenge to patients and clinicians alike. Recognition of the psychosocial impact should prompt involvement of mental health specialists, counsellors, and social workers in patient management. Inconsistencies in definition (two or three consecutive miscarriages) confound research in RM. Although endocrinological, thrombotic, autoimmune, and uterine structural perturbations have been described in association with RM, antiphospholipid syndrome and embryonic karyotype abnormalities remain the two closest conditions for which a reasonable explanation can be offered to patients along with prognostication for future pregnancies. A diagnosis of RM has additional implications, not only for previable pregnancy loss, but an association with adverse obstetric and future maternal health outcomes. A global consensus on the definition of RM, along with phenotypic characterization of this heterogeneous condition would improve interpretation of available data and future research. A thorough understanding of the underlying molecular pathophysiological mechanisms in specific phenotypic categories of RM is the fundamental requisite for the advancement of this field.

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