Endogenous retroviruses regulate periimplantation placental growth and differentiation

被引:193
作者
Dunlap, Kathrin A.
Palmarini, Massimo
Varela, Mariana
Burghardt, Robert C.
Hayashi, Kanako
Farmer, Jennifer L.
Spencer, Thomas E. [1 ]
机构
[1] Texas A&M Univ, Ctr Anim Biotechnol & Genom, Dept Anim Sci, College Stn, TX 77843 USA
[2] Texas A&M Univ, Image Anal Lab, Dept Vet Integrat Biosci, College Stn, TX 77843 USA
[3] Univ Glasgow, Sch Vet, Inst Comparat Med, Glasgow G61 1QH, Lanark, Scotland
基金
英国惠康基金;
关键词
development; placenta; sheep; trophectoderm;
D O I
10.1073/pnas.0603836103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Endogenous retroviruses (ERVs) are fixed and abundant in the genomes of vertebrates. Circumstantial evidence suggests that ERVs play a role in mammalian reproduction, particularly placental morphogenesis, because intact ERV envelope genes were found to be expressed in the syncytiotrophoblasts of human and mouse placenta and to elicit fusion of cells in vitro. We report here in vivo and in vitro experiments finding that the envelope of a particular class of ERVs of sheep, endogenous Jaagsiekte sheep retroviruses (enJSRVs), regulates trophectoderm growth and differentiation in the periimplantation conceptus (embryo/fetus and associated extraembryonic membranes). The enJSRV envelope gene is expressed in the trophectoderm of the elongating ovine conceptus after day 12 of pregnancy. Loss-of-function experiments were conducted in utero by injecting morpholino antisense oligonucleotides on day 8 of pregnancy that blocked enJSRV envelope protein production in the conceptus trophectoderm. This approach retarded trophectoderm outgrowth during conceptus elongation and inhibited trophoblast giant binucleate cell differentiation as observed on day 16. Pregnancy loss was observed by day 20 in sheep receiving morpholino antisense oligonucleotides. In vitro inhibition of the enJSRV envelope reduced the proliferation of mononuclear trophectoderm cells isolated from day 15 conceptuses. Consequently, these results demonstrate that the enJSRV envelope regulates trophectoderm growth and differentiation in the periimplantation ovine conceptus. This work supports the hypothesis that ERVs play fundamental roles in placental morphogenesis and mammalian reproduction.
引用
收藏
页码:14390 / 14395
页数:6
相关论文
共 43 条
[1]   CHANGES IN OVINE CONCEPTUS AND ENDOMETRIAL FUNCTION FOLLOWING ASYNCHRONOUS EMBRYO TRANSFER OR ADMINISTRATION OF PROGESTERONE [J].
ASHWORTH, CJ ;
BAZER, FW .
BIOLOGY OF REPRODUCTION, 1989, 40 (02) :425-433
[2]  
BAZER FW, 1979, J ANIM SCI, V49, P1522
[3]   Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution [J].
Blaise, S ;
de Parseval, N ;
Bénit, L ;
Heidmann, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :13013-13018
[4]   An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor [J].
Blond, JL ;
Lavillette, D ;
Cheynet, V ;
Bouton, O ;
Oriol, G ;
Chapel-Fernandes, S ;
Mandrand, B ;
Mallet, F ;
Cosset, FL .
JOURNAL OF VIROLOGY, 2000, 74 (07) :3321-3329
[5]   Identification of differentially regulated genes during elongation and early implantation in the ovine trophoblast using complementary DNA array screening [J].
Cammas, L ;
Reinaud, P ;
Dubois, O ;
Bordas, N ;
Germain, G ;
Charpigny, G .
BIOLOGY OF REPRODUCTION, 2005, 72 (04) :960-967
[6]  
DeMartini JC, 2003, CURR TOP MICROBIOL, V275, P117
[7]   Ovine endogenous betaretroviruses (enJS']JSRVs) and placental morphogenesis [J].
Dunlap, K. A. ;
Palmarini, M. ;
Spencer, T. E. .
PLACENTA, 2006, 27 :S135-S140
[8]   Sheep endogenous betaretroviruses (enJS']JSRVs) and the hyaluronidase 2 (HYAL2) receptor in the ovine uterus and conceptus [J].
Dunlap, KA ;
Palmarini, M ;
Adelson, DL ;
Spencer, TE .
BIOLOGY OF REPRODUCTION, 2005, 73 (02) :271-279
[9]   Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae [J].
Dupressoir, A ;
Marceau, G ;
Vernochet, C ;
Bénit, L ;
Kanellopoulos, C ;
Sapin, V ;
Heidmann, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (03) :725-730
[10]  
FAN H, 2003, JAAGSIEKTE SHEEP RET