Loss of function of endothelin-2 leads to reduced ovulation and CL formation

Joseph A. Cacioppo, Sang Wook Oh, Hey Young Kim, Jongki Cho, Po Ching Patrick Lin, Masashi Yanagisawa, Che Myong Ko

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere96115
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 24 2014

Fingerprint

Endothelin-2
endothelins
Corpus Luteum
Ovulation
corpus luteum
ovulation
Gonadotropins
mice
gonadotropins
Endothelin A Receptors
Endothelin Receptors
Peptides
Ovary
Histology
peptides
Progesterone
Gene Knockout Techniques
Muscle
receptors
superovulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Cacioppo, J. A., Oh, S. W., Kim, H. Y., Cho, J., Lin, P. C. P., Yanagisawa, M., & Ko, C. M. (2014). Loss of function of endothelin-2 leads to reduced ovulation and CL formation. PloS one, 9(4), [e96115]. https://doi.org/10.1371/journal.pone.0096115

Loss of function of endothelin-2 leads to reduced ovulation and CL formation. / Cacioppo, Joseph A.; Oh, Sang Wook; Kim, Hey Young; Cho, Jongki; Lin, Po Ching Patrick; Yanagisawa, Masashi; Ko, Che Myong.

In: PloS one, Vol. 9, No. 4, e96115, 24.04.2014.

Research output: Contribution to journalArticle

Cacioppo, JA, Oh, SW, Kim, HY, Cho, J, Lin, PCP, Yanagisawa, M & Ko, CM 2014, 'Loss of function of endothelin-2 leads to reduced ovulation and CL formation', PloS one, vol. 9, no. 4, e96115. https://doi.org/10.1371/journal.pone.0096115
Cacioppo JA, Oh SW, Kim HY, Cho J, Lin PCP, Yanagisawa M et al. Loss of function of endothelin-2 leads to reduced ovulation and CL formation. PloS one. 2014 Apr 24;9(4). e96115. https://doi.org/10.1371/journal.pone.0096115
Cacioppo, Joseph A. ; Oh, Sang Wook ; Kim, Hey Young ; Cho, Jongki ; Lin, Po Ching Patrick ; Yanagisawa, Masashi ; Ko, Che Myong. / Loss of function of endothelin-2 leads to reduced ovulation and CL formation. In: PloS one. 2014 ; Vol. 9, No. 4.
@article{0f419de9391b4ad7b55c67a1892752d3,
title = "Loss of function of endothelin-2 leads to reduced ovulation and CL formation",
abstract = "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.",
author = "Cacioppo, {Joseph A.} and Oh, {Sang Wook} and Kim, {Hey Young} and Jongki Cho and Lin, {Po Ching Patrick} and Masashi Yanagisawa and Ko, {Che Myong}",
year = "2014",
month = "4",
day = "24",
doi = "10.1371/journal.pone.0096115",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Loss of function of endothelin-2 leads to reduced ovulation and CL formation

AU - Cacioppo, Joseph A.

AU - Oh, Sang Wook

AU - Kim, Hey Young

AU - Cho, Jongki

AU - Lin, Po Ching Patrick

AU - Yanagisawa, Masashi

AU - Ko, Che Myong

PY - 2014/4/24

Y1 - 2014/4/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84899738359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899738359&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0096115

DO - 10.1371/journal.pone.0096115

M3 - Article

C2 - 24763822

AN - SCOPUS:84899738359

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e96115

ER -