Actions of a nitric oxide donor on prostaglandin production and angiogenic activity in the equine endometrium
Rosário P. Roberto da Costa A , Ana S. Costa B , Anna J. Korzekwa C , Rafal Platek C , Marta Siemieniuch C , António Galvão B C , Dale A. Redmer D , José Robalo Silva B , Dariusz J. Skarzynski C and Graça Ferreira-Dias B EA Department of Animal Sciences, Escola Superior Agrária de Coimbra, Bencanta, 3040-316 Coimbra, Portugal.
B Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Technical University of Lisbon, 1300-477 Lisboa, Portugal.
C Institute of Animal Reproduction and Food Research, 10-747 Olsztyn, Poland.
D Department of Animal and Range Sciences, North Dakota State University, Fargo, ND 58105-5727, USA.
E Corresponding author. Email: gmlfdias@fmv.utl.pt
Reproduction, Fertility and Development 20(6) 674-683 https://doi.org/10.1071/RD08015
Submitted: 29 January 2008 Accepted: 21 April 2008 Published: 9 July 2008
Abstract
Nitric oxide (NO) plays an important role in prostaglandin secretion and angiogenesis in the reproductive system. In the present study, the roles of the NO donor spermine NONOate and tumour necrosis factor-α (TNF; as a positive control) in prostaglandin production and angiogenic activity of equine endometria during the oestrous cycle were evaluated. In addition, the correlation between NO production and the expression of key prostaglandin synthase proteins was determined. The protein expression of prostaglandin F synthase (PGFS) increased in early and mid-luteal stages, whereas that of prostaglandin E synthase (PGES) was increased in the early luteal stage. The in vitro release of NO was highest after ovulation. There was a high correlation between NO production and PGES expression, as well as NO release and PGFS expression. There were no differences detected in prostaglandin H synthase 2 (PTGS-2) throughout the oestrous cycle and there was no correlation between PTGS-2 expression and NO. In TNF- or spermine-treated endometria, the expression of prostaglandin (PG) E2 increased in the early and mid-luteal phases, whereas that of PGF2α increased in the follicular and late luteal phases. Bovine aortic endothelial cell (BAEC) proliferation was stimulated in TNF-treated follicular-phase endometria. However, in spermine-treated endometria, NO delivered from its donor had no effect, or even an inhibitory effect, on BAEC proliferation. In conclusion, despite no change in PTGS-2 expression throughout the oestrous cycle in equine endometrial tissue, there were changes observed in the expression of PGES and PGFS, as well as in the production of PGE2 and PGF2α. In the mare, NO is involved in the secretory function of the endometrium, modulating PGE2 and PGF2α production. Even though TNF caused an increase in the production of angiogenic factors and prostaglandins, its complex action in mare uterus should be elucidated.
Additional keywords: angiogenesis, mare, tumour necrosis factor.
Acknowledgements
This work was supported by grants ‘CIISA 75/Angiogénese/Apoptose’ from CIISA and POCTI/CVT/39519/2001 from Fundação para a Ciência e Tecnologia (FCT), Portugal, Polish Academy of Sciences (Badania Statutowe ZIR 2007; PAN Olsztyn, Poland) and the International Project of Polish Ministry of Science and Higher Education (PORTUGALIA/78/2007). Marta Siemieniuch received a grant from the Foundation for Polish Science. The authors thank Dr Paula M. Serrão for technical assistance and Dr K. Watanabe (Division of Applied Life Sciences, Graduate School of Integrated Sciences and Arts, University of East Asia, Shimonoseki, Yamaguchi, Japan) for the antibody against PGFS and PGES.
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