title: Downregulation of miR-199a-5p Disrupts the Developmental Potential of In Vitro-Fertilized Mouse Blastocysts.
abstract: Although in vitro fertilization (IVF), one of the most effective and successful assisted reproductive technologies, is widely used for treating infertility and in animal breeding, increasing evidence indicates that IVF offspring are linked to various short- or long-term consequences. Erroneous epigenetic modifications induced by IVF are suspected of contributing to these consequences. Among these epigenetic modifications, microRNAs may affect embryo implantation and early postimplantation development. Here, we performed comparative microRNA profiling between in vivo-fertilized (IVO group) and in vitro-fertilized (IVF group) mouse embryos at Embryonic Day 3.5 (E3.5) and E7.5. Our dynamic analyses showed that the dysregulated microRNAs were mainly associated with the regulation of genes involved in carcinogenesis, genetic information processing, glucose metabolism, cytoskeleton organization, and neurogenesis. Further analysis showed that miR-199a-5p was consistently downregulated in IVF embryos compared with their IVO counterparts. Through gain- and loss-of-function experiments, we demonstrated that IVF-induced downregulation of miR-199a-5p results in a higher glycolytic rate and lower developmental potential of IVF blastocysts, including cell lineage misallocation and lower fetal survival post implantation. Therefore, preventing downregulation of miR-199a-5p may become an effective strategy for improving the development of IVF peri-implantation embryos in the future.
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Miao
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China anleim@cau.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China tianjh@cau.edu.cn.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D019070:Cell Lineage / Q000502:physiology; D015536:Down-Regulation; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D006019:Glycolysis / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse
keywords: development; glycolysis; hexokinase 2; in vitro fertilization; miR-199a-5p; microRNA sequencing