Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 May 15;99(10):2342–2350. doi: 10.1172/JCI119415

Detection of ebaf, a novel human gene of the transforming growth factor beta superfamily association of gene expression with endometrial bleeding.

R Kothapalli 1, I Buyuksal 1, S Q Wu 1, N Chegini 1, S Tabibzadeh 1
PMCID: PMC508072  PMID: 9153275

Abstract

Human endometrium is unique since it is the only tissue in the body that bleeds at regular intervals. In addition, abnormal endometrial bleeding is one of the most common manifestations of gynecological diseases, and is a prime indication for hysterectomy. Here, we report on a novel human gene, endometrial bleeding associated factor (ebaf), whose strong expression in endometrium was associated with abnormal endometrial bleeding. In normal human endometrium, this gene was transiently expressed before and during menstrual bleeding. In situ hybridization showed that the mRNA of ebaf was expressed in the stroma without any significant mRNA expression in the endometrial glands or endothelial cells. The predicted protein sequence of ebaf showed homology with and structural features of the members of TGF-beta superfamily. Fluorescence in situ hybridization showed that the ebaf gene is located on human chromosome 1 at band q42.1. Thus, ebaf is a novel member of the TGF-beta superfamily and an endometrial tissue factor whose expression is associated with normal menstrual and abnormal endometrial bleeding.

Full Text

The Full Text of this article is available as a PDF (550.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Archer D. F., Pickar J. H., Bottiglioni F. Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group. Obstet Gynecol. 1994 May;83(5 Pt 1):686–692. [PubMed] [Google Scholar]
  2. Bayer S. R., DeCherney A. H. Clinical manifestations and treatment of dysfunctional uterine bleeding. JAMA. 1993 Apr 14;269(14):1823–1828. [PubMed] [Google Scholar]
  3. Bouillet P., Oulad-Abdelghani M., Vicaire S., Garnier J. M., Schuhbaur B., Dollé P., Chambon P. Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK-2/Eplg2). Dev Biol. 1995 Aug;170(2):420–433. doi: 10.1006/dbio.1995.1226. [DOI] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Daopin S., Piez K. A., Ogawa Y., Davies D. R. Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. Science. 1992 Jul 17;257(5068):369–373. doi: 10.1126/science.1631557. [DOI] [PubMed] [Google Scholar]
  6. Finn C. A. Why do women and some other primates menstruate? Perspect Biol Med. 1987 Summer;30(4):566–574. doi: 10.1353/pbm.1987.0007. [DOI] [PubMed] [Google Scholar]
  7. Fraser I. S., Hickey M., Song J. Y. A comparison of mechanisms underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception. Hum Reprod. 1996 Oct;11 (Suppl 2):165–178. doi: 10.1093/humrep/11.suppl_2.165. [DOI] [PubMed] [Google Scholar]
  8. Hadjeb N., Berkowitz G. A. Preparation of T-over-hang vectors with high PCR product cloning efficiency. Biotechniques. 1996 Jan;20(1):20–22. doi: 10.2144/96201bm02. [DOI] [PubMed] [Google Scholar]
  9. Hallberg L., Högdahl A. M., Nilsson L., Rybo G. Menstrual blood loss--a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45(3):320–351. doi: 10.3109/00016346609158455. [DOI] [PubMed] [Google Scholar]
  10. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  11. JACOBS A., BUTLER E. B. MENSTRUAL BLOOD-LOSS IN IRON-DEFICIENCY ANAEMIA. Lancet. 1965 Aug 28;2(7409):407–409. doi: 10.1016/s0140-6736(65)90757-9. [DOI] [PubMed] [Google Scholar]
  12. Jones C. M., Simon-Chazottes D., Guenet J. L., Hogan B. L. Isolation of Vgr-2, a novel member of the transforming growth factor-beta-related gene family. Mol Endocrinol. 1992 Nov;6(11):1961–1968. doi: 10.1210/mend.6.11.1480182. [DOI] [PubMed] [Google Scholar]
  13. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Liang P., Bauer D., Averboukh L., Warthoe P., Rohrwild M., Muller H., Strauss M., Pardee A. B. Analysis of altered gene expression by differential display. Methods Enzymol. 1995;254:304–321. doi: 10.1016/0076-6879(95)54022-9. [DOI] [PubMed] [Google Scholar]
  15. Liang P., Pardee A. B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 1992 Aug 14;257(5072):967–971. doi: 10.1126/science.1354393. [DOI] [PubMed] [Google Scholar]
  16. Marchuk D., Drumm M., Saulino A., Collins F. S. Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res. 1991 Mar 11;19(5):1154–1154. doi: 10.1093/nar/19.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McDonald N. Q., Hendrickson W. A. A structural superfamily of growth factors containing a cystine knot motif. Cell. 1993 May 7;73(3):421–424. doi: 10.1016/0092-8674(93)90127-c. [DOI] [PubMed] [Google Scholar]
  18. McPherron A. C., Lee S. J. GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J Biol Chem. 1993 Feb 15;268(5):3444–3449. [PubMed] [Google Scholar]
  19. Meno C., Saijoh Y., Fujii H., Ikeda M., Yokoyama T., Yokoyama M., Toyoda Y., Hamada H. Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos. Nature. 1996 May 9;381(6578):151–155. doi: 10.1038/381151a0. [DOI] [PubMed] [Google Scholar]
  20. Miller M. A., Kolb P. E., Raskind M. A. A method for simultaneous detection of multiple mRNAs using digoxigenin and radioisotopic cRNA probes. J Histochem Cytochem. 1993 Dec;41(12):1741–1750. doi: 10.1177/41.12.8245421. [DOI] [PubMed] [Google Scholar]
  21. Ober W. B. Effects of oral and intrauterine administration of contraceptives on the uterus. Hum Pathol. 1977 Sep;8(5):513–527. doi: 10.1016/s0046-8177(77)80112-3. [DOI] [PubMed] [Google Scholar]
  22. Panoskaltsis-Mortari A., Bucy R. P. In situ hybridization with digoxigenin-labeled RNA probes: facts and artifacts. Biotechniques. 1995 Feb;18(2):300–307. [PubMed] [Google Scholar]
  23. Rodgers W. H., Matrisian L. M., Giudice L. C., Dsupin B., Cannon P., Svitek C., Gorstein F., Osteen K. G. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones. J Clin Invest. 1994 Sep;94(3):946–953. doi: 10.1172/JCI117461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tabibzadeh S. Cytokines and the hypothalamic-pituitary-ovarian-endometrial axis. Hum Reprod. 1994 May;9(5):947–967. doi: 10.1093/oxfordjournals.humrep.a138621. [DOI] [PubMed] [Google Scholar]
  26. Tabibzadeh S. Signals and molecular pathways involved in apoptosis, with special emphasis on human endometrium. Hum Reprod Update. 1995 Jul;1(4):303–323. doi: 10.1093/humupd/1.4.303. [DOI] [PubMed] [Google Scholar]
  27. Tabibzadeh S. The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodelling. Mol Hum Reprod. 1996 Feb;2(2):77–92. doi: 10.1093/molehr/2.2.77. [DOI] [PubMed] [Google Scholar]
  28. Wathen P. I., Henderson M. C., Witz C. A. Abnormal uterine bleeding. Med Clin North Am. 1995 Mar;79(2):329–344. doi: 10.1016/s0025-7125(16)30071-2. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES