Home LiteratureArticle Details
PMID: 20357223 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Identification of a novel role for endothelins within the oviduct.

Endocrinology ·Vol. 151 ·No. 6 ·2010-06-00 ·Pages 2858-67

Jeoung M, Lee S, Hawng HK, Cheon YP, Jeong YK, Gye MC, Iglarz M, Ko C, Bridges PJ

Abstract

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.

MeSH Terms
Animals CCAAT-Binding Factor/genetics,physiology Chorionic Gonadotropin/pharmacology Embryonic Development/physiology Endothelins/genetics,metabolism Female Fertilization in Vitro Gonadotropins, Equine/pharmacology Immunohistochemistry Interleukin-10/genetics,physiology Mice Oligonucleotide Array Sequence Analysis Oviducts/drug effects,metabolism Polymerase Chain Reaction Pyridines/pharmacology RNA, Messenger/genetics Receptor, Endothelin A/genetics,metabolism Receptor, Endothelin B/genetics,metabolism Tetrazoles/pharmacology Transforming Growth Factor beta/genetics,physiology
Chemicals
CCAAT-Binding Factor Chorionic Gonadotropin Endothelins Gonadotropins, Equine Pyridines RNA, Messenger Receptor, Endothelin A Receptor, Endothelin B Tetrazoles Transforming Growth Factor beta Interleukin-10 tezosentan
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jeoung Myoungkun
Division of Clinical and Reproductive Sciences, University of Kentucky, Lexington, Kentucky 40536, USA.
Lee Sungeun
Hawng Hee-Kyung
Cheon Yong-Pil
Jeong Youn Kyung
Gye Myung Chan
Iglarz Marc
Ko Chemyong
Bridges Phillip J
References (69)
69 references, click to expand
  1. Role of hypoxia in the regulation of periovulatory EDN2 expression in the mouse.
    Can J Physiol Pharmacol. 2008 Jun;86(6):310-9 PMID: 18516093
  2. CCAAT/enhancer-binding protein alpha (C/EBP alpha) inhibits cell proliferation through the p21 (WAF-1/CIP-1/SDI-1) protein.
    Genes Dev. 1996 Apr 1;10(7):804-15 PMID: 8846917
  3. Improved in vitro fertilization and development by use of modified human tubal fluid and applicability of pronucleate embryos for cryopreservation by rapid freezing in inbred mice.
    Comp Med. 2004 Oct;54(5):564-70 PMID: 15575371
  4. Human tubal secretion can modify the affinity of human spermatozoa for the zona pellucida.
    Fertil Steril. 2009 Feb;91(2):407-13 PMID: 18295213
  5. [Transforming growth factor-beta1, estradiol, progesterone and lutropin levels in follicular fluid after ovarian stimulation].
    Di Yi Jun Yi Da Xue Xue Bao. 2003 May;23(5):463-5 PMID: 12754131
  6. Control of the secretory cell cycle in cat oviduct by estradiol and progesterone.
    Am J Anat. 1981 Oct;162(2):107-18 PMID: 7304467
  7. The fallopian tube and reproductive health.
    J Pediatr Adolesc Gynecol. 1999 Aug;12(3):121-6 PMID: 10546902
  8. Endothelin-1/endothelin-3 ratio: a potential prognostic factor of pulmonary arterial hypertension.
    Chest. 2007 Jan;131(1):101-8 PMID: 17218562
  9. Endothelin-2 is a hypoxia-induced autocrine survival factor for breast tumor cells.
    Mol Cancer Ther. 2002 Dec;1(14):1273-81 PMID: 12516960
  10. Structural basis of the function of endothelin receptor.
    Mol Cell Biochem. 1999 Jan;190(1-2):153-6 PMID: 10098982
  11. Endothelin-3 is a novel neuropeptide: isolation and sequence determination of endothelin-1 and endothelin-3 in porcine brain.
    Biochem Biophys Res Commun. 1989 Oct 16;164(1):587-93 PMID: 2508640
  12. Endothelin-1 promotes cell survival in renal cell carcinoma through the ET(A) receptor.
    Cancer Lett. 2007 Feb 8;246(1-2):139-48 PMID: 16581180
  13. Cloning of full-length preproendothelin-2 cDNA and its expression in dog.
    J Vet Med Sci. 2003 Nov;65(11):1217-25 PMID: 14665752
  14. Local roles of TGF-beta superfamily members in the control of ovarian follicle development.
    Anim Reprod Sci. 2003 Oct 15;78(3-4):165-83 PMID: 12818643
  15. Aquaporin7 expression during perinatal development of mouse brain.
    Neurosci Lett. 2006 Dec 1;409(2):106-11 PMID: 17052846
  16. C/EBPbeta is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma.
    Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1870-5 PMID: 16439483
  17. Endothelin production by bovine oviduct epithelial cells.
    J Reprod Fertil. 1994 May;101(1):27-30 PMID: 8064689
  18. Characterization of endothelin receptors in the anterior pituitary gland.
    Am J Physiol. 1993 Oct;265(4 Pt 1):E601-8 PMID: 8238336
  19. Development and application of a rat ovarian gene expression database.
    Endocrinology. 2004 Nov;145(11):5384-96 PMID: 15297439
  20. Potential role of nitric oxide in endothelin-1 provoked inhibition of progesterone secretion by isolated ovarian granulosa cells.
    Endocr Regul. 2002 Mar;36(1):19-22 PMID: 11971747
  21. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology.
    Pharmacol Rev. 1994 Sep;46(3):325-415 PMID: 7831383
  22. Inhibition of prolactin secretion by endothelin-3 is pertussis toxin-sensitive.
    Eur J Pharmacol. 1991 Jun 6;198(2-3):223-5 PMID: 1907563
  23. Endothelin-2 induces oviductal contraction via endothelin receptor subtype A in rats.
    J Endocrinol. 2007 Jun;193(3):383-91 PMID: 17535876
  24. Secreted proteins of the oviduct.
    Cells Tissues Organs. 2000;166(2):165-79 PMID: 10729726
  25. Gestational age-dependent expression of IL-10 and its receptor in human placental tissues and isolated cytotrophoblasts.
    J Immunol. 2000 Jun 1;164(11):5721-8 PMID: 10820249
  26. Cyclic changes in the ampulla of the rat oviduct.
    J Exp Zool. 1996 Oct 1;276(2):164-73 PMID: 8900079
  27. Diagnosis of female infertility. A comprehensive approach.
    J Reprod Med. 1989 Jan;34(1):29-40 PMID: 2649667
  28. Endothelin-3 inhibits prolactin and stimulates LH, FSH and TSH secretion from pituitary cell culture.
    Biochem Biophys Res Commun. 1991 Jan 15;174(1):338-43 PMID: 1899191
  29. CCAAT/enhancer binding protein alpha (C/EBPalpha) is an important mediator of mouse C/EBPbeta protein isoform production.
    Hepatology. 1999 Feb;29(2):597-601 PMID: 9918941
  30. Lipopolysaccharide-induced interleukin-10 in mice: role of endogenous tumor necrosis factor-alpha.
    Eur J Immunol. 1995 Oct;25(10):2888-93 PMID: 7589088
  31. Cyclic regulation of transcription factor C/EBP beta in human endometrium.
    Reprod Biol Endocrinol. 2009 Feb 17;7:15 PMID: 19222842
  32. Endothelins: multifunctional renal peptides.
    Physiol Rev. 1993 Apr;73(2):375-411 PMID: 8475194
  33. Endocrine response in the fallopian tube.
    Endocr Rev. 1984 Fall;5(4):525-51 PMID: 6094174
  34. Recent developments in endocrinology and paracrinology of blastocyst implantation in the primate.
    Hum Reprod Update. 1998 Mar-Apr;4(2):153-68 PMID: 9683352
  35. Assisted reproductive technology surveillance - United States, 2004.
    MMWR Surveill Summ. 2007 Jun 8;56(6):1-22 PMID: 17557073
  36. Abundance of endothelin-3 in rat intestine, pituitary gland and brain.
    Biochem Biophys Res Commun. 1989 Oct 16;164(1):74-80 PMID: 2508641
  37. Endothelin is an autocrine regulator of prolactin secretion.
    Endocrinology. 1998 Dec;139(12):5164-73 PMID: 9832457
  38. The endothelin axis: a novel target for pharmacotherapy of female malignancies.
    Curr Vasc Pharmacol. 2007 Jul;5(3):239-48 PMID: 17627567
  39. Localization and role of endothelin-1 and endothelin receptors in the human Fallopian tube.
    Mol Hum Reprod. 2001 Nov;7(11):1057-63 PMID: 11675472
  40. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility.
    Science. 2009 May 15;324(5929):938-41 PMID: 19443782
  41. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine.
    Fertil Steril. 1994 Jan;61(1):1-17 PMID: 7507444
  42. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice.
    Cell. 1994 Dec 30;79(7):1267-76 PMID: 8001159
  43. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons.
    Cell. 1994 Dec 30;79(7):1277-85 PMID: 8001160
  44. Endothelin-1 inhibits apoptosis in prostate cancer.
    Neoplasia. 2005 Jul;7(7):631-7 PMID: 16026642
  45. Immunocytochemical localization of endothelin in cultured bovine endothelial cells.
    Histochemistry. 1990;94(5):475-7 PMID: 2283310
  46. Mechanisms underlying endothelin's inhibition of FSH-stimulated progesterone production by ovarian granulosa cells.
    Mol Cell Endocrinol. 1999 Oct 25;156(1-2):169-78 PMID: 10612435
  47. A novel potent vasoconstrictor peptide produced by vascular endothelial cells.
    Nature. 1988 Mar 31;332(6163):411-5 PMID: 2451132
  48. Ovarian contractility and ovulation.
    Res Reprod. 1974 Mar;6(2):3-4 PMID: 12257206
  49. Peptide growth factors and preimplantation development.
    Hum Reprod Update. 1997 Mar-Apr;3(2):137-57 PMID: 9286738
  50. Oviductal regulation of fertilization and early embryonic development.
    J Reprod Fertil Suppl. 1997;52:285-300 PMID: 9602736
  51. Rat ovarian granulosa cell as a site of endothelin reception and action: attenuation of gonadotropin-stimulated steroidogenesis via perturbation of the A-kinase signaling pathway.
    Biol Reprod. 1994 Nov;51(5):1058-65 PMID: 7849183
  52. Human fallopian tube expresses transforming growth factor (TGF beta) isoforms, TGF beta type I-III receptor messenger ribonucleic acid and protein, and contains [125I]TGF beta-binding sites.
    J Clin Endocrinol Metab. 1994 Oct;79(4):1177-84 PMID: 7962292
  53. Endothelin-2 in ovarian follicle rupture.
    Endocrinology. 2006 Apr;147(4):1770-9 PMID: 16410304
  54. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.
    Proc Natl Acad Sci U S A. 1989 Apr;86(8):2863-7 PMID: 2649896
  55. Contractility of the human fallopian tube.
    Basic Life Sci. 1974;4(PT. B):139-45 PMID: 4461022
  56. Cloning and expression of a cDNA encoding an endothelin receptor.
    Nature. 1990 Dec 20-27;348(6303):730-2 PMID: 2175396
  57. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  58. Expression of TGF-beta s and TGF-beta type II receptor mRNAs in mouse folliculogenesis: stored maternal TGF-beta 2 message in oocytes.
    Biochem Biophys Res Commun. 1994 Jun 15;201(2):649-56 PMID: 8002998
  59. Immunohistochemical localization of transforming growth factor-beta in human implantation sites.
    J Clin Endocrinol Metab. 1994 Mar;78(3):592-6 PMID: 7510303
  60. Human embryonic behavior in a sequential human oviduct-endometrial coculture system.
    Fertil Steril. 1994 May;61(5):976-8 PMID: 8174741
  61. Endothelin expression in the uterus.
    J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):209-14 PMID: 7626456
  62. The endothelin axis: emerging role in cancer.
    Nat Rev Cancer. 2003 Feb;3(2):110-6 PMID: 12563310
  63. Quantification of transforming growth factor beta1 (TGFbeta1) mRNA expression in mouse preimplantation embryos and determination of TGFbeta receptor (type I and type II) expression in mouse embryos and reproductive tract.
    Mol Hum Reprod. 2001 Nov;7(11):1047-56 PMID: 11675471
  64. Transactivation of the epidermal growth factor receptor in endothelin-1-induced mitogenic signaling in human ovarian carcinoma cells.
    Cancer Res. 2000 Sep 15;60(18):5310-7 PMID: 11016663
  65. Endothelins.
    N Engl J Med. 1995 Aug 10;333(6):356-63 PMID: 7609754
  66. CCAAT/enhancer binding protein alpha regulates p21 protein and hepatocyte proliferation in newborn mice.
    Mol Cell Biol. 1997 Dec;17(12):7353-61 PMID: 9372966
  67. Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice.
    Development. 1998 Mar;125(5):813-24 PMID: 9449664
  68. Reciprocal regulation of adipogenesis by Myc and C/EBP alpha.
    Science. 1992 Apr 17;256(5055):379-82 PMID: 1566086
  69. Expression and cyclic change of betaglycan in the rat oviduct.
    J Reprod Dev. 2009 Apr;55(2):200-5 PMID: 19145066
Article Info
Journal
Endocrinology
Abbr.
Endocrinology
ISSN
1945-7170
DOI
10.1210/en.2009-1155
Published
2010-06-00
Epub
2010-00-31
Pages
2858-67
Language
English
Region
United States
NLM ID
0375040
PMCID
PMC2875811
Subset
IM
Grants
NICHD NIH HHS · R01HD052694 · United States
NCRR NIH HHS · P20 RR015592 · United States
NIDA NIH HHS · K12 DA014040 · United States
NCRR NIH HHS · P20 RR15592 · United States
NICHD NIH HHS · R01 HD052694 · United States
External Links
PubMed source DOI: 10.1210/en.2009-1155 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2