Skip to main content

Advertisement

SpringerLink
Log in

Increased Expression of ac-FoxO1 Protein in Prelabor Fetal Membranes Overlying the Cervix: Possible Role in Human Fetal Membrane Rupture

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Forkhead box O proteins have critical roles in a number of cellular processes, including apoptosis. Acetylation and phosphorylation of forkhead box O proteins are posttranslational modifications that attenuate their transcriptional activity. As supracervical fetal membranes are characterized by increased cell death, the aim of this study was to compare the expression of forkhead box O1, acetylatedforkhead box O1, and Ser–25 6 phosphorylatedforkhead box O1 at supracervical and distal site fetal membrane. Fetal membranes overlying the cervix were identified in situ in women undergoing term elective Caesarean section. Immuno-histochemistry (n = 7) was used to analyze the protein expression of forkhead box O1, acetylatedforkhead box O1, and Ser–256 phosphorylated forkhead box O1. There was no difference in forkhead box O1 and Ser–25 6 phosphorylated forkhead box O1 protein expression between the 2 sites. However, when compared with distal site, the intensity and extent of staining of acetylatedforkhead box O1 were greater in amnion and chorion obtained from the supracervical site. In summary, supracervical fetal membranes are characterized by increased acetylatedforkhead box O1 protein expression. Although the precise role and contribution of acetylatedforkhead box O1 in the process of human fetal membrane rupture are unknown, it has been implicated in apoptosis and/or cell cycle regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Glistrap LC III. Parturition: biomolecular and physiological processes. In: Williams Obstetrics. 19th ed. Stamford: Appleton and Lange; 1993:345–356.

  2. Murphy DJ, Fowlie PW, McGuire W. ABC of preterm birth: obstetric issues in preterm birth. BMJ. 2006;329:783–786.

    Article  Google Scholar 

  3. Moore RM, Mansour JM, Redline RW, Mercer BM, Moore JJ. The physiology of fetal membrane rupture: insight gained from the determination of physical properties. Placenta. 2006;27:1037–1051.

    Article  CAS  Google Scholar 

  4. Reti NG, Lappas M, Riley C, et al. Why do membranes rupture at term? Evidence of increased cellular apoptosis in the supra-cervical fetal membranes. Am J Obstet Gynecol. 2007; 196:484.e1–484.e10.

  5. Lappas M, Odumetse TL, Riley C, et al. Pre-labour fetal membranes overlying the cervix display alterations in inflammation and NF-kB signalling pathways. Placenta. 2008;29:995–1002.

    Article  CAS  Google Scholar 

  6. McLaren J, Taylor DJ, Bell SC. Increased incidence of apoptosis in non-labour-affected cytotrophoblast cells in term fetal membranes overlying the cervix. Hum Reprod. 1999;14:2895–2900.

    Article  CAS  Google Scholar 

  7. McLaren J, Malak TM, Bell SC. Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix. Hum Reprod. 1999;14:237–241.

    Article  CAS  Google Scholar 

  8. McLaren J, Taylor DJ, Bell SC. Increased concentration of pro-matrix metalloproteinase 9 in term fetal membranes overlying the cervix before labor: Implications for membrane remodelling and rupture. Am J Obstet Gynecol. 2000;182:409–416.

    Article  CAS  Google Scholar 

  9. McParland PC, Taylor DJ, Bell SC. Mapping of zones of altered morphology and chorionic connective tissue cellular phenotype in human fetal membranes overlying the lower uterine pole and cervix before labor at term. Am J Obstet Gynecol. 2003;189:1481–1488.

    Article  Google Scholar 

  10. El Khwad M, Stetzer RM, Moore RM, et al. Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor. Biol Reprod. 2005;72:720–726.

    Article  CAS  Google Scholar 

  11. Malak TM, Mulholland G, Bell SC. Structural and morpho-metric characteristics of the fetal membranes in preterm birth. J Reprod Fertil. 1993;12:48.

    Google Scholar 

  12. Malak TM, Bell SC. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet Gynaecol. 1994;101:375–386.

    Article  CAS  Google Scholar 

  13. El Khwad M, Pandey V, Stetzer B, Mercer B, Kumar D, Moore RM. Fetal membranes from term vaginal deliveries have a zone of weakness exhibiting characteristics of apoptosis and remodelling. J Soc Gynecol Invest. 2006;13:191–195.

    Article  Google Scholar 

  14. Mansour JM, Moore JJ. Fetal membranes from term vaginal deliveries have a zone of weakness exhibiting characteristics of apoptosis and remodelling. J Soc Gynecol Invest. 2006;13:191–195.

    Article  Google Scholar 

  15. Lappas M, Lim R, Riley C, Rice GE, Permezel M. Localisation and expression of FoxO1 proteins in human gestational tissues. Placenta 2009;30:256–262.

  16. Birkenkamp KU, Coffer PJ. FOXO transcription factors as regulators of immune homeostasis: molecules to die for? J Immunol. 2003;171:1623–1629.

    Article  CAS  Google Scholar 

  17. van der Horst A, Burgering BM. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007;8:440–450.

    Article  Google Scholar 

  18. Accili D, Arden K. FoxOs at the Crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004;17:421–426.

    Article  Google Scholar 

  19. Vogt PK, Jiang H, Aoki M. Triple layer control: phosphory-lation, acetylation and ubiquitination of FOXO proteins. Cell Cycle. 2005;4:908–913.

    Article  CAS  Google Scholar 

  20. Zhao X, Gan L, Pan H, et al. Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14–3–3-dependent and -independent mechanisms. Biochem J. 2004;378:839–849.

    Article  CAS  Google Scholar 

  21. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA. JNK regulates lifespan in Caenorhabditis ele-gans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A. 2005;102:4494–4499.

    Article  CAS  Google Scholar 

  22. Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 dea-cetylase. Science. 2004;303:2011–2015.

    Article  CAS  Google Scholar 

  23. Perrot V, Rechler MM. The coactivator p300 directly acety-lates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. Mol Endocrinol. 2005;19:2283–2298.

    Article  CAS  Google Scholar 

  24. Van Der Heide LP, Smidt M. Regulation of FoxO activity by CBP/p300-mediated acetylation. Trends Biochem Sci. 2005;30:81–86.

    Article  Google Scholar 

  25. Lam EWF, Francis RE, Petkovic M. FOXO transcription factors: key regulators of cell fate. Biochem Soc Trans. 2006;34:722–726.

    Article  CAS  Google Scholar 

  26. Armes JE, Trute L, White S, et al. Distinct molecular patho-geneses of early-onset breast cancer in BRCA1 and BRCA2 mutation carriers: a population-based study. Cancer Res. 1999;59:2011–2017.

    CAS  PubMed  Google Scholar 

  27. Woods JR. Reactive oxygen species and preterm premature rupture of membranes-a review. Placenta. 2001;22:S38–S44.

    Article  Google Scholar 

  28. Stuart EL, Evans GS, Lin YS, Powers HJ. Reduced collagen and ascorbic acid concentrations and increased proteolytic susceptibility with prelabor fetal membrane rupture in women. Biol Reprod. 2005;72:230–235.

    Article  CAS  Google Scholar 

  29. Behl Y, Krothapalli P, Desta T, Roy S, Graves DT. Enhanced FOXO1 activation mediated by TNF induces retinal micro-vascular cell apoptosis and microvascular cell loss in type 1 diabetic retinopathy. Diabetes. 2008;57:A15.

  30. Tang TT, Dowbenko D, Jackson A, et al. The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor. J Biol Chem. 2002;277:14255–14265.

    Article  CAS  Google Scholar 

  31. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857–868.

    Article  CAS  Google Scholar 

  32. Guo S, Rena G, Cichy S, He X, Cohen P, Unterman T. Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein–1 promoter activity through a conserved insulin response sequence. J Biol Chem. 1999;274:17184–17192.

    Article  CAS  Google Scholar 

  33. Bendon RW. Histopathology of fetal membrane rupture: a review of the literature. Semin Perinatol. 1996;20:381–388.

    Article  CAS  Google Scholar 

  34. Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ. Expression of the pro-apoptotic Bcl–2 family member Bim is regulated by the Forkhead transcription factor FKHR-L1. Curr Biol. 2000;10:1201–1204.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Melbourne, and Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg (ML, MP); and Translational Proteomics, Level 4/163 Studley Road, Melbourne, 3084, Victoria, Australia

    Martha Lappas PhD, Clyde Riley B App Sci FAIMS, Greg E. Rice PhD & Michael Permezel MD, FRANZCOG

Authors
  1. Martha Lappas PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clyde Riley B App Sci FAIMS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Greg E. Rice PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Permezel MD, FRANZCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martha Lappas PhD.

Additional information

Dr Martha Lappas is in recipient of a National Health and Medical Research Council (NHMRC) RD Wright Fellowship (grant no 454777). The work described in this manuscript was funded by the Melbourne Research Grant Scheme and ANZ Charitable Trust (Medical Research and Technology Grant). Funding for the Leica Qwin Image Analysis System was provided by the Medical Research Foundation for Women and Babies. The authors gratefully acknowledge the assistance of the Clinical Research Midwives Valerie Bryant and Sarah Mitchell, the Obstetrics and Midwifery staff of the Mercy Hospital for Women for their cooperation, and Dr Nicole Reti (from the Department of Obstetrics & Gynaecology, University of Melbourne, Mercy Hospital for Women) for her assistance with the sample collection.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lappas, M., Riley, C., Rice, G.E. et al. Increased Expression of ac-FoxO1 Protein in Prelabor Fetal Membranes Overlying the Cervix: Possible Role in Human Fetal Membrane Rupture. Reprod. Sci. 16, 635–641 (2009). https://doi.org/10.1177/1933719109332831

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719109332831

Key words

Search

Navigation