title: mir-34b/c and mir-449a/b/c are required for spermatogenesis, but not for the first cleavage division in mice.
abstract: Mammalian sperm are carriers of not only the paternal genome, but also the paternal epigenome in the forms of DNA methylation, retained histones and noncoding RNAs. Although paternal DNA methylation and histone retention sites have been correlated with protein-coding genes that are critical for preimplantation embryonic development, physiological evidence of an essential role of these epigenetic marks in fertilization and early development remains lacking. Two miRNA clusters consisting of five miRNAs (miR-34b/c and miR-449a/b/c) are present in sperm, but absent in oocytes, and miR-34c has been reported to be essential for the first cleavage division in vitro. Here, we show that both miR-34b/c- and miR-449-null male mice displayed normal fertility, and that intracytoplasmic injection of either miR-34b/c- or miR-449-null sperm led to normal fertilization, normal preimplantation development and normal birth rate. However, miR-34b/c and miR-449 double knockout (miR-dKO) males were infertile due to severe spermatogenic disruptions and oligo-astheno-teratozoospermia. Injection of miR-dKO sperm into wild-type oocytes led to a block at the two-pronucleus to zygote transition, whereas normal preimplantation development and healthy pups were obtained through injection of miR-dKO round spermatids. Our data demonstrate that miR-34b/c and miR-449a/b/c are essential for normal spermatogenesis and male fertility, but their presence in sperm is dispensable for fertilization and preimplantation development.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Shuiqiao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Huili
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA wyan@medicine.nevada.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
keywords: Epigenetics; Fertility; Germ cell; Reproduction; Spermatogenesis