title: Actin Disorganization Plays a Vital Role in Impaired Embryonic Development of In Vitro-Produced Mouse Preimplantation Embryos.
abstract: Assisted reproductive technology (ART) is being increasingly applied to overcome infertility. However, the in vitro production process, the main procedure of ART, can lead to aberrant embryonic development and health-related problems in offspring. Understanding the mechanisms underlying the ART-induced side effects is important to improve the ART process. In this study, we carried out comparative transcriptome profiling between in vivo- (IVO) and in vitro- produced (IVP) mouse blastocysts. Our results suggested that aberrant actin organization might be a major factor contributing to the impaired development of IVP embryos. To test this, we examined the effect of actin disorganization on the development of IVP preimplantation embryos. Specific disruption of actin organization by cytochalasin B (CB) indicated that well-organized actin is essential for in vitro embryonic development. Supplementing the culture medium with 10(-9) M melatonin, a cytoskeletal modulator in adult somatic cells, significantly reversed the disrupted expression patterns of genes related to actin organization, including Arhgef2, Bcl2, Coro2b, Flnc, and Palld. Immunofluorescence analysis showed that melatonin treatment of IVP embryos significantly improved the distribution and organization of actin filaments (F-actin) from the 8-cell stage onwards. More importantly, we found that melatonin alleviated the CB-mediated aberrant F-actin distribution and organization and rescued CB-induced impaired embryonic development. This is the first study to indicate that actin disorganization is implicated in impaired development of IVP embryos during the preimplantation stage. We also demonstrated that improving actin organization is a promising strategy to optimize existing IVP systems.
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Zhen-Ni
authors.initials: ZN
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Miao
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Sui
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Shu-Zhi
authors.initials: SZ
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Jing-Zhou
authors.initials: JZ
authors.lastname: Nie
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Zhong-Hong
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, P. R. China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Tian
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology*; D003571:Cytochalasin B / Q000494:pharmacology*; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D017423:Sequence Analysis, RNA
chemical_list: D000199:Actins; D003571:Cytochalasin B; D008550:Melatonin