title: Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.
abstract: Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function.
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan School of Health Sciences, Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Naruse
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ono
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan School of Health Sciences, Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Irie
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Faculty of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, The Japan Mouse Clinic, RIKEN BRC, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Furuse
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Department of Biological Sciences, Asahikawa Medical University, 2-1-1-1 Midorigaoka-higashi, Asahikawa 078-8510, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hino
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata 951-8585, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Oda
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, The Japan Mouse Clinic, RIKEN BRC, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Misho
authors.initials: M
authors.lastname: Kashimura
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, The Japan Mouse Clinic, RIKEN BRC, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yamada
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, The Japan Mouse Clinic, RIKEN BRC, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Niigata 951-8585, Japan.
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan Global Center of Excellence Program for International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan fishino.epgn@mri.tmd.ac.jp tkanekoi@is.icc.u-tokai.ac.jp.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.affiliation: School of Health Sciences, Tokai University, Bohseidai, Isehara, Kanagawa 259-1193, Japan fishino.epgn@mri.tmd.ac.jp tkanekoi@is.icc.u-tokai.ac.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaneko-Ishino
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D015735:Mifepristone; D036801:Parturition / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010928:Placental Lactogen / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D017931:DNA Primers; D015735:Mifepristone; D011374:Progesterone; D010928:Placental Lactogen
keywords: Evolution; Gestation; Parturition; Placenta; Progesterone; Retrotransposon