Abstract

The development of the placental fold, which increases the maternal–fetal interacting surface area, is of primary importance for the growth of the fetus throughout the whole pregnancy. However, the mechanisms involved remain to be fully elucidated. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) are a new class of RNAs with regulatory functions and could be epigenetically regulated by histone modifications. In this study, 141 lncRNAs (including 73 up-regulated and 68 down-regulated lncRNAs) were identified to be differentially expressed in the placentas of pigs during the establishment and expanding stages of placental fold development. The differentially expressed lncRNAs and genes (DElncRNA-DEgene) co-expression network analysis revealed that these differentially expressed lncRNAs (DElncRNAs) were mainly enriched in pathways of cell adhesion, cytoskeleton organization, epithelial cell differentiation and angiogenesis, indicating that the DElncRNAs are related to the major events that occur during placental fold development. In addition, we integrated the RNA-seq (RNA sequencing) data with the ChIP-seq (chromatin immunoprecipitation sequencing) data of H3K4me3/H3K27ac produced from the placental samples of pigs from the two stages (gestational days 50 and 95). The analysis revealed that the changes in H3K4me3 and/or H3K27ac levels were significantly associated with the changes in the expression levels of 37 DElncRNAs. Furthermore, several H3K4me3/H3K27ac-lncRNAs were characterized to be significantly correlated with genes functionally related to placental development. Thus, this study provides new insights into understanding the mechanisms for the placental development of pigs.

Highlights

  • The placenta is an organ that provides nutrients and oxygen to the developing fetus during pregnancy

  • 690 putative long non-coding RNAs (lncRNAs) were identified to be expressed in porcine placentas tissues) on gestational days 50 and 95

  • A total of 141 lncRNAs were found to be differentially expressed in placentas gestational days 50 and 95, including 73 up-regulated and between gestational days 50 and 95, including 73 up68 down-regulated lncRNAs on gestational days 95 (Figure 1 and Table S3)

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Summary

Introduction

The placenta is an organ that provides nutrients and oxygen to the developing fetus during pregnancy. The pig has an epitheliochorial type of placenta, in which the trophoblast epithelial layer interdigitates with the maternal endometrial epithelial layer to form the folded bilayer [1]. Around gestational day 50 (the gestational length is about 114 days in pigs), the placental fold development reaches a temporary steady state. Thereafter, as gestation progresses, the placental fold increases in depth or complexity to further expand the exchange surface area [2,3,4,5]. The placental fold development is a critical contributor to maintaining the function of porcine placentas. Fetal loss and depression in piglet birth weight are primary factors associated with reproductive performance and were demonstrated to be mainly caused by placental dysfunction [6,7,8,9]. Many genes and factors have been reported to be involved in the development of the porcine placental fold [3,4,10,11], the mechanism for porcine placental development remains to be fully elucidated

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