Loss of function of endothelin-2 leads to reduced ovulation and CL formation.
Endothelin-2 (EDN2), a potent vasoconstrictive peptide, is transiently produced by periovulatory follicles at the time of ovulation when corpus luteum (CL) formation begins. EDN2 induces contraction of ovarian smooth muscles ex vivo via an endothelin receptor A-mediated pathway. In this study, we aimed to determine if EDN2 is required for normal ovulation and subsequent CL formation in?vivo. In the ovaries of a mouse model that globally lacks the Edn2 gene (Edn2 knockout mouse; Edn2KO), histology showed that post-pubertal Edn2KO mice possess follicles of all developmental stages, but no corpora lutea. When exogenous gonadotropins were injected to induce super-ovulation, Edn2KO mice exhibited significantly impaired ovulation and CL formation compared to control littermates. Edn2KO ovaries that did ovulate in response to gonadotropins did not contain histologically and functionally identifiable CL. Intra-ovarian injection of EDN2 peptide results suggest partial induction of ovulation in Edn2KO mice. Endothelin receptor antagonism in wild type mice similarly disrupted ovulation, CL formation, and progesterone secretion. Overall, this study suggests that EDN2 is necessary for normal ovulation and CL formation.
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America.
Joseph A
JA
Cacioppo
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America; Department of Biology Education, Institute of Fusion Science, Chonbuk National University, Jeonju, South Korea.
Sang Wook
SW
Oh
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America.
Hey-young
HY
Kim
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America; College of Veterinary Medicine, Research Institute of Veterinary Medicine, Chungnam National University, Daejon, South Korea.
Jongki
J
Cho
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America.
Po-Ching Patrick
PC
Lin
Howard Hughes Medical Institute and Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Masashi
M
Yanagisawa
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America.
CheMyong
C
Ko
D000818:Animals; D003338:Corpus Luteum / Q000002:abnormalities* / Q000098:blood supply / Q000502:physiology; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019333:Endothelin-2 / Q000378:metabolism*; D005260:Female; D006062:Gonadotropins / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D006080:Ovarian Follicle / Q000166:cytology; D010060:Ovulation / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019333:Endothelin-2; D006062:Gonadotropins