Submitted to: Endocrine Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/1998
Publication Date: N/A
Citation: Interpretive Summary: Reproductive failure is one of the most costly factors influencing the livestock industry. A large majority of reproductive losses in sheep occur during early pregnancy as a result of failed implantation. The objective of this research is to investigate the biological signal (transforming growth factor beta, TGFbeta) produced by the sheep embryo and maternal endometrium during implantation. In cultures of sheep embryos, TGFbeta increased dramatically from day 12 to day 16 of pregnancy and in cultures of uterine endometrium, TGFbeta remained relatively stable. Results indicate that TGFbeta production by the embryo occurs after maternal recognition of pregnancy and coincides with implantation. Complete understanding of embryo implantation should increase embryo survival and improve lambing rates for the U.S. sheep industry.
Technical Abstract: The transforming growth factor beta (TGFbeta) family is known to control cell migration, growth, differentiation, function and regulation of extracellular matrix, all of which are required for the process of implantation. Expression of TGFbeta by the conceptus and endometrium was studied during the period of implantation in the ewe. A total of thirty- four ewes were hysterectomized on d 12, 14, 16, 18 or 20 of pregnancy (d 0 = day of estrus). Conceptus (200 mg wet wt) and endometrial (300 mg wet wt) tissues were cultured in vitro in 7 and 10 ml Eagle's minimal essential medium, respectively. The culture media were subjected to a bioassay to determine concentrations of TGFbeta. Conceptus culture media (CCM) were also analyzed for contents of ovine interferon-tau (oIFNtau). Whole uteri including conceptus(es) and conceptuses (d 16) only were fixed and subjected to immunohistochemical and in situ hybridization studies. Levels of oIFNtau produced by conceptuses were the highest on d 16 at 1.4 ug/ml. Concentrations of TGFbeta in d 12, 14, 16, 18 and 20 CCM were 38, 102, 862, 728 and 336 pg/ml, respectively. Immunohistochemical studies revealed that d 16 conceptuses displayed major staining for TGFbeta-1, no beta-2 and minor staining for beta-3. In situ hybridization studies also revealed that d 16 trophectoderm possessed most TGFbeta-1 mRNA while d 14 trophectoderm and d 20 chorion/amnion displayed weaker staining for TGFbeta-1 mRNA. TGFbeta in d 12, 14, 16, 18 and 20 endometrial culture media was 156, 129, 49, 62 and 179 pg/ml, respectively. These results indicate that TGFbeta production by the conceptus coincides with the time when oIFNtau production starts to decline. These observations support the postulate that TGFbeta may play an important role in implantation in the ovine species.