Published online before print July 18, 2007
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*Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada; and Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada
@ To whom correspondence should be addressed. E-mail: ctayade{at}uoguelph.ca.
Peri-implantation and midgestational fetal losses reduce potential litter sizes up to 40% in commercial swine. Peri-implantation studies [gestation days (gd)15-23] of porcine RNA from laser capture microdissected uterine lymphocytes and biopsies of mesometrial endometrium and trophoblast previously linked gd21-23 fetal arrest with transcriptional deficits in vascular endothelial growth factor (VEGF) and its regulatory factor, hypoxia inducible factor (HIF)-1
, and with elevations in IFN-
and TNF- and suggested endometrial lymphocytes played a pivotal, proangiogenic role in fetal survival. Here, we address more comprehensively porcine endometrial angiogenesis by comparing transcription between endometrial endothelium and lymphocytes during early (gd20) and midgestation (gd50) losses and by incorporation of histopathology and protein immunolocalization of VEGF, placenta growth factor (PlGF), VEGF receptor I (VEGFRI), and VEGFRII. In healthy sites, endometrial lymphocytes transcribed more VEGF at gd50 than gd20, and transcripts were more abundant in lymphocytes than in endothelium or trophoblast. Arterial endothelial cells showed the most abundant transcription of PlGF. With fetal arrest, maternal transcripts for VEGF but not PlGF dropped, and fetal transcripts remained relatively stable. Maternal and fetal HIF-1 transcription declined. Lymphocytes preferentially transcribed VEGFRI over VEGFRII, and endometrial arterial endothelium and trophoblast preferentially transcribed VEGFRII. IFN- and TNF- transcripts were present in gd20 and gd50 healthy- and arresting-implantation sites. gd20 arrest was associated with greater transcription of IFN- than TNF- in maternal and fetal tissues. At gd50, this was reversed. Endometrial, vascular pathology was evident only at gd50. These data suggest the critical importance for lymphocyte-driven endometrial angiogenesis, which extends to midgestation.
Key Words: endothelium • pregnancy • proinflammatory cytokines • trophoblast • vascular endothelial growth factor
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