Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer

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 c...

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Autores principales:	Shuheng Yang, Wei Zheng, Chen Yang, Ruowen Zu, Shiyu Ran, Huan Wu, Mingkun Mu, Simin Sun, Nana Zhang, Rick F. Thorne, Yichun Guan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	in vitro fertilization-embryo transfer placenta differentially expressed genes MiRNA-mRNA next-generation sequencing Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/9924fae717494d27a61d50a4f2c0d4a9
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spelling	oai:doaj.org-article:9924fae717494d27a61d50a4f2c0d4a92021-11-11T12:02:35ZIntegrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer1664-239210.3389/fendo.2021.774997https://doaj.org/article/9924fae717494d27a61d50a4f2c0d4a92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.774997/fullhttps://doaj.org/toc/1664-2392ObjectiveSupraphysiological 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.Shuheng YangWei ZhengChen YangRuowen ZuShiyu RanHuan WuMingkun MuSimin SunNana ZhangRick F. ThorneRick F. ThorneYichun GuanFrontiers Media S.A.articlein vitro fertilization-embryo transferplacentadifferentially expressed genesMiRNA-mRNAnext-generation sequencingDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	in vitro fertilization-embryo transfer placenta differentially expressed genes MiRNA-mRNA next-generation sequencing Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	in vitro fertilization-embryo transfer placenta differentially expressed genes MiRNA-mRNA next-generation sequencing Diseases of the endocrine glands. Clinical endocrinology RC648-665 Shuheng Yang Wei Zheng Chen Yang Ruowen Zu Shiyu Ran Huan Wu Mingkun Mu Simin Sun Nana Zhang Rick F. Thorne Rick F. Thorne Yichun Guan Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
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.
format	article
author	Shuheng Yang Wei Zheng Chen Yang Ruowen Zu Shiyu Ran Huan Wu Mingkun Mu Simin Sun Nana Zhang Rick F. Thorne Rick F. Thorne Yichun Guan
author_facet	Shuheng Yang Wei Zheng Chen Yang Ruowen Zu Shiyu Ran Huan Wu Mingkun Mu Simin Sun Nana Zhang Rick F. Thorne Rick F. Thorne Yichun Guan
author_sort	Shuheng Yang
title	Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
title_short	Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
title_full	Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
title_fullStr	Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
title_full_unstemmed	Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer
title_sort	integrated analysis of hub genes and micrornas in human placental tissues from in vitro fertilization-embryo transfer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9924fae717494d27a61d50a4f2c0d4a9
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Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer

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