Identification of a novel role for endothelins within the oviduct.
Endothelins were first identified as potent vasoactive peptides; however, diversity in the biological function of these hormones is now evident. We have identified a novel role for endothelins: a requirement for these peptides within the oviduct during fertilization and/or early embryo development. In vivo, treatment after ovulation with a dual endothelin receptor antagonist (tezosentan) decreased the number of two-cell embryos that could be collected from within the oviducts. In vitro fertilization experiments showed that gamete viability and their ability to fertilize were not affected by treatment with this antagonist, suggesting that the effect observed in vivo was mediated by the oviduct itself. Expression of mRNA for all three isoforms of the endothelins and both receptor subtypes was detectable within the oviduct. Expression of mRNA for endothelin-3 was regulated by gonadotropins in epithelial cells of the oviduct and increased specifically within the isthmus of this structure. Immunostaining revealed localization of both endothelin receptors A and B to the columnar epithelial cells within the oviduct, suggestive of a local role for endothelins in the regulation of epithelial function and ultimately oviductal secretions. A microarray analysis revealed three likely endothelin-regulated protein networks for future analysis: the TGFbeta, IL-10, and CCAAT/enhancer-binding protein superfamilies. Overall, these results suggest a novel and requisite role for endothelins within the oviduct during fertilization and/or early embryo development.
Jeoung
Myoungkun
M
Division of Clinical and Reproductive Sciences, University of Kentucky, Lexington, Kentucky 40536, USA.
Lee
Sungeun
S
Hawng
Hee-Kyung
HK
Cheon
Yong-Pil
YP
Jeong
Youn Kyung
YK
Gye
Myung Chan
MC
Iglarz
Marc
M
Ko
Chemyong
C
Bridges
Phillip J
PJ
D000818:Animals; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D047108:Embryonic Development / Q000502:physiology; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010057:Oviducts / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology
D023081:CCAAT-Binding Factor; D006063:Chorionic Gonadotropin; D016232:Endothelins; D006064:Gonadotropins, Equine; D011725:Pyridines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; C120582:tezosentan