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The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer.

ABSTRACT: BACKGROUND:The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). METHODS:This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools. RESULTS:A total of 3405 differentially regulated genes were identified as significantly dysregulated (>?2-fold change; P

SUBMITTER: Zhao L

PROVIDER: S-EPMC6604150 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer.

Zhao Liang L Zheng Xiuli X Liu Jingfang J Zheng Rong R Yang Rui R Wang Ying Y Sun Lifang L

Reproductive biology and endocrinology : RB&E 20190701 1

<h4>Background</h4>The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET).<h4>Methods</h4>This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated ...[more]

PMID: 31262321

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Project description:The mechanisms underlying the potential risks of in vitro fertilization and embryo transfer (IVF-ET) have not been fully elucidated. The aim of this study was to explore changes in the complement and coagulation pathways in placentae subjected to IVF-ET in the first trimester compared to placentae from normal pregnancies. Four placenta samples in the first trimester were obtained from patients undergoing IVF-ET owing to oviductal factors only. An additional 4 control placentae were obtained from volunteers with normal pregnancies. A GeneChip Affymetrix HG-U133 Plus 2.0 Array was utilized to analyze the changes in gene expression between the normal and IVF-ET placentae. Differentially expressed genes (DEGs) were analyzed using the Database for Annotation and Visualization and Integrated Discovery bioinformatics resource, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Using real-time PCR, we confirmed the obtained microarray data in 10 dysregulated genes. Five of the gene products were further analyzed by immunohistochemistry (IHC) to determine their protein expression and localization. A total of fifty DEGs were identified in the complement and coagulation pathways in the IVF-ET treated placentae: 38 upregulated and 12 down-regulated. KEGG pathway analysis indicated that IVF-ET manipulation substantially over-activated the coagulation and complement pathways, while urokinase plasminogen activator- and urokinase plasminogen activator receptor-mediated trophoblastic invasion and tissue remodeling were inhibited. Furthermore, the 5 proteins analyzed by IHC were found to be localized specifically to the placenta. This is the first study to compare DEGs relating to the placental complement and coagulation pathways from patients undergoing IVF-ET treatment compared to those undergoing normal pregnancy. These findings identified valuable biomarkers and potential novel therapeutic targets to combat the unfavorable effects of IVF-ET.

Project description:The mechanism underlying the potential risk associated with in vitro fertilization and embryo transfer (IVF?ET) has been previously investigated but remains to be fully elucidated. As the placenta is a critical organ that sustains and protects the fetus, this is an important area of research. The aim of the present study was to determine the difference in trophoblast cell function in the first trimester between naturally conceived pregnancies and pregnancies achieved via IVF?ET therapy. A total of 20 placental villi in first trimester samples were obtained through fetal bud aspiration from patients undergoing IVF?ET due to oviductal factors between January 2016 and August 2018. In addition, a further 20 placental villi were obtained from those who naturally conceived and had normal pregnancies but were undergoing artificial abortion; these patients were recruited as the controls. Reverse transcription?quantitative (RT?q)PCR and semi?quantitative immunohistochemical methods were used to detect the mRNA and protein expression of ??fetoprotein (AFP), vascular endothelial growth factor (VEGF), transferrin (TF), tubulin ?1 class VI (TUBB1), metallothionein 1G (MT1G), BCL2, glial cells missing transcription factor 1 (GCM1), epidermal growth factor (EGF) receptor (EGFR), PTEN and leukocyte associated immunoglobulin like receptor 2 (LAIR2) in villi from both groups. Differentially expressed genes were analyzed using Search Tool for the Retrieval of Interacting Genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted. The RT?qPCR data revealed that the mRNA expression levels of AFP, VEGF and TF were significantly higher in the IVF?ET group than in the control group (P<0.05), and those of TUBB1, MT1G, BCL2, GCM1, EGFR, PTEN and LAIR2 were significantly lower (P<0.05). These gene products were expressed in the placental villus tissues, either in the cytoplasm, or in the membrane of syncytiotrophoblast and cytotrophoblast cells. The immunohistochemistry results were in line with those observed using RT?qPCR. KEGG pathway analysis indicated that the trophoblast cell function of the IVF?ET group in the first trimester was different from naturally conceived pregnancies with regard to proliferation, invasion, apoptosis and vascular development. The IVF?ET process may trigger adaptive placental responses, and these compensatory mechanisms could be a risk for certain diseases later in life.

Project description:BACKGROUND:Development of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood. METHODS:RNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth. RESULTS:RNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation. CONCLUSIONS:This study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.

Project description:Increasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011-2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34-7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42-6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12-10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle.

Project description:ObjectiveSupraphysiological hormone exposure, in vitro culture and embryo transfer throughout the in vitro fertilization-embryo transfer (IVF-ET) procedures may affect placental development. The present study aimed to identify differences in genomic expression profiles between IVF-ET and naturally conceived placentals and to use this as a basis for understanding the underlying effects of IVF-ET on placental function.MethodsFull-term human placental tissues were subjected to next-generation sequencing to determine differentially expressed miRNAs (DEmiRs) and genes (DEGs) between uncomplicated IVF-ET assisted and naturally conceived pregnancies. Gene ontology (GO) enrichment analysis and transcription factor enrichment analysis were used for DEmiRs. MiRNA-mRNA interaction and protein-protein interaction (PPI) networks were constructed. In addition, hub genes were obtained by using the STRING database and Cytoscape. DEGs were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed miRNAs were validated through qRT-PCR.ResultsCompared against natural pregnancies, 12 DEmiRs and 258 DEGs were identified in IVF-ET placental tissues. In a validation cohort, it was confirmed that hsa-miR-204-5p, hsa-miR-1269a, and hsa-miR-941 were downregulation, while hsa-miR-4286, hsa-miR-31-5p and hsa-miR-125b-5p were upregulation in IVF-ET placentas. Functional analysis suggested that these differentially expressed genes were significantly enriched in angiogenesis, pregnancy, PI3K-Akt and Ras signaling pathways. The miRNA-mRNA regulatory network revealed the contribution of 10 miRNAs and 109 mRNAs while EGFR was the most highly connected gene among ten hub genes in the PPI network.ConclusionEven in uncomplicated IVF-ET pregnancies, differences exist in the placental transcriptome relative to natural pregnancies. Many of the differentially expressed genes in IVF-ET are involved in essential placental functions, and moreover, they provide a ready resource of molecular markers to assess the association between placental function and safety in IVF-ET offspring.

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The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer.

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The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer.

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