P-540 Improper placentation due to skewed Oct4-Cdx2 expression may be a leading factor in idiopathic recurrent pregnancy loss (RPL) cases from Assam, India.

نویسندگان

چکیده

Abstract Study question Does the differential expression of key embryonic stem cell (ESC) markers due to upstream signaling cascade(s) deregulation influence RPL pathogenesis in studied population? Summary answer Imbalanced Oct4-Cdx2 linked ESCs polarization β-catenin during peri-implantation period impacts population. What is known already affects approximately 2-5% women globally and around 7% Indian reproductive age group; with 50% case etiology being unclear. Proper placentation indispensable for establishment, continuation, success a pregnancy; it depends largely on healthy balance between apoptosis differentiation that aids proper trophoblast invasion. These events are tightly controlled by interplay oxygen tension, hormones, growth factors, other molecules most importantly transcription factors including those deciding lineage like Oct4, NANOG, Cdx2, wherein, enhance Oct-4 activity ESCs. design, size, duration The sample size was predicted using Raosoft software utilizing prevalence rate RPL. Overall 87 2 or more pregnancy losses before completion 20 weeks gestation were enrolled as cases informed consent, whereas, control group, 107 volunteers undergoing medical termination (MTP) gestation-week-matched comparative study group experimental data analysis. Participants/materials, setting, methods Products conception (POC) collected from MTP cases. POCs 2vials every subject: (i) 4% buffered formalin fixation preparation microscopic slides immunofluorescence (IF) based protein Oct4 Cdx2; (ii) RNA later solution site specific transcriptional analysis Realtime PCR. difference analyzed SPSS statistical software. Main results role chance IF confirmed higher OCT4 compared controls, whereas CDX2 found be low subjects. PCR amplification cDNA β-actin internal normalization (25.76 ± 10.17 folds) NANOG (18.32 6.67folds) showed increased Cdx2 downregulated (0.487 0.186 indicating shift towards pluripotency which non-favorable environment ongoing since initiation different lineages required at time gestation. cdx2 oct4 correlated inversely significantly {Pearson’s correlation= −0.838, p = 0.009; Spearman’s rho= −0.786; 0.016}. realtime β-catenin, molecule involved direct enhancing controls. Statistically, β-catenin-Oct4 positively significantly. Limitations, reasons caution Being patient study, present limited an associative only; therefore secondary validation causal association lines suitable model system futuristically may add valuable scientific inputs aid clinical intervention modalities controlling Wider implications findings As majority undefined limiting possibilities interventions we presume can layout possible therapeutic regulating regulators influencing skewed ESC profile aiding leading successful subpopulation history. Trial registration number Not applicable

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ژورنال

عنوان ژورنال: Human Reproduction

سال: 2023

ISSN: ['1460-2350', '0268-1161']

DOI: https://doi.org/10.1093/humrep/dead093.881