P-319 Transcriptomic analysis reveals deregulated molecular mechanisms related to miscarriage, preeclampsia, and pregnancy complications during gestational endometrial phase in adenomyosis

Abstract Study question Is there any molecular deregulation in the gestational endometrium of women with adenomyosis responsible for adenomyosis-related pregnancy disorders? Summary answer Women show deregulated mechanisms their phase involved miscarriage, preeclampsia, and complications, causing infertility. What is known already are characterized by having defective decidualization, altered endometrial receptivity, impaired embryo-maternal communication, implantation failure higher risk preeclampsia miscarriage. However, underlying these infertility-related conditions remain unknown, mainly due to inaccessibility obtaining maintaining tissues. We have previously established organoids differentiated them into phase, demonstrating maintenance disease-specific traits. For this reason, here we use organoid platform describe during adenomyosis-associated disorders, which could be possible infertility therapeutical targets. design, size, duration Endometrial from eutopic non-disease (control) (n = 15/group) were (ADENO-GESTorg CONTROL-GESTorg) supplementation ovarian hormones. An RNA-sequencing was performed. DESeq2 used identify differentially expressed genes (DEGs), FDR < 0.05. GO KEGG analysis performed study DEGs implication at biologically functional level. QIAGEN Ingenuity Pathway Analysis (IPA) further upregulated downregulated pathways. Participants/materials, setting, methods biopsies obtained hysteroscopy control patients IVI Valencia Clinics. Patients between 18≤45 years old BMI≤28 kg/m2 diagnosed (adenomyosis group) or without nor other uterine pathologies (control included study. Main results role chance identified 1999 (153 1846 downregulated) ADENO- compared CONTROL-GESTorg. Between genes, CXCL14 restricts trophoblast invasion outgrowth, CYP24A1 increased spontaneous miscarriage preeclamptic placentas, PTAFR induces preterm delivery mice (log2 Fold Change [log2FC] 1.6, 2.4, 0.8). Among PGR expression has been related severe recurrent loss, whereas defects on ZWINT, ESCO2 MCM6 associated high incidence aneuploidy, leading infertility, newborn disorders (log2FC −2.21, -2.57, -2.53, -2.48). Functional showed functions as blastocyst growth, utero embryonic development, developmental maturation response oxidative stress, standing out involvement disorders. IPA predicted a significant inhibition D-myo-inositol metabolism (z score [z] −0.7) affecting oocyte embryo quality, VEGF signaling −1.5) disturbing adaptation hypoxia, ERK/MAPK −4.0) lethality placental alterations; activation PPARα/RXRα 0.5) that gives rise p53 1.1) preeclampsia-complicated pregnancies, RHOGDI PTEN 3.6, 3.4) both promoting preeclampsia. Limitations, reasons caution Although platforms faithfully recapitulate tissue origin characteristics well traits, they still vitro models need translated vivo studies corroborate obtained. Wider implications findings Molecular adenomyosis. These therapeutic target develop pharmacological treatments ameliorate Trial registration number not applicable