( development |
placenta |
sheep |
trophectoderm )
*Center for Animal Biotechnology and Genomics, Department of Animal Science, and
Edited by George E. Seidel, Jr., Colorado State University, Fort Collins, CO, and approved August 8, 2006 (received for review May 10, 2006) 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.
Developmental Biology
Endogenous retroviruses regulate periimplantation placental growth and differentiation
, , 
, 
Image Analysis Laboratory, Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843; and Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow G61 1QH, United Kingdom
Author contributions: K.A.D., M.P., M.V., and T.E.S. designed research; K.A.D., M.P., M.V., R.C.B., K.H., J.L.F., and T.E.S. performed research; M.P., M.V., R.C.B., K.H., J.L.F., and T.E.S. contributed new reagents/analytic tools; K.A.D., M.P., M.V., and T.E.S. analyzed data; and K.A.D., M.P., and T.E.S. wrote the paper.
The authors declare no conflict of interest.
To whom correspondence should be addressed.
www.pnas.org/cgi/doi/10.1073/pnas.0603836103
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
This article has been cited by other articles in HighWire Press-hosted journals:
|
|
 |
|
  T. E Spencer, O. Sandra, and E. Wolf Genes involved in conceptus-endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches Reproduction, February 1, 2008; 135(2): 165 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Blomberg, K. Hashizume, and C. Viebahn Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation Reproduction, February 1, 2008; 135(2): 181 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Farmer, R. C. Burghardt, F. D. Jousan, P. J. Hansen, F. W. Bazer, and T. E. Spencer Galectin 15 (LGALS15) functions in trophectoderm migration and attachment FASEB J, February 1, 2008; 22(2): 548 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mangeney, M. Renard, G. Schlecht-Louf, I. Bouallaga, O. Heidmann, C. Letzelter, A. Richaud, B. Ducos, and T. Heidmann Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins PNAS, December 18, 2007; 104(51): 20534 - 20539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K Lewis, J. L Farmer, R. C Burghardt, G. R Newton, G. A Johnson, D. L Adelson, F. W Bazer, and T. E Spencer Galectin 15 (LGALS15): A Gene Uniquely Expressed in the Uteri of Sheep and Goats that Functions in Trophoblast Attachment Biol Reprod, December 1, 2007; 77(6): 1027 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Arnaud, P. R. Murcia, and M. Palmarini Mechanisms of Late Restriction Induced by an Endogenous Retrovirus J. Virol., October 15, 2007; 81(20): 11441 - 11451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Reiss, Y. Zhang, and D. L. Mager Widely variable endogenous retroviral methylation levels in human placenta Nucleic Acids Res., July 9, 2007; 35(14): 4743 - 4754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, R. C. Burghardt, F. W. Bazer, and T. E. Spencer WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development Endocrinology, July 1, 2007; 148(7): 3496 - 3506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Anthony and J. D. Cantlon Ribonucleic acid interference: A new approach to the in vivo study of gene function J Anim Sci, March 1, 2007; 85(13_suppl): E18 - E19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Murcia, F. Arnaud, and M. Palmarini The Transdominant Endogenous Retrovirus enJS56A1 Associates with and Blocks Intracellular Trafficking of Jaagsiekte Sheep Retrovirus Gag J. Virol., February 15, 2007; 81(4): 1762 - 1772. [Abstract] [Full Text] [PDF]
|
|
