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J Clin Endocrinol Metab. 2014 Oct;99(10):E1913-21. doi: 10.1210/jc.2014-1340. Epub 2014 Jun 24.

Dysregulated sphingolipid metabolism in endometriosis.

Author information

1
BioSym (Y.H.L., C.W.T., A.V., L.G., S.R.T.) and Infectious Diseases Inter-Disciplinary Research Groups (Y.H.L., L.C., S.R.T.), Singapore-MIT Alliance for Research and Technology, Singapore 138602; Saw Swee Hock School of Public Health (C.S.T.), National University of Singapore, Singapore 117597; Department of Reproductive Medicine (S.F.L., J.K.Y.C.), KK Women's and Children's Hospital, Singapore 229899; Departments of Biological Engineering (L.G.) and Chemistry (S.R.T.) and Center for Gynepathology Research (L.G.), Massachusetts Institute of Technology, Boston, Massachusetts 02139; Department of Obstetrics and Gynecology (J.K.Y.C.), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228; and Cancer and Stem Cell Biology Program (J.K.Y.C.), Duke-NUS Medical School, Singapore 169857.

Abstract

BACKGROUND:

In endometriosis, the establishment and subsistence of ectopic lesions outside the endometrium suggest an altered cellular state for pathological hyperplasia. Sphingolipids are bioactive compounds, and their biosynthesis and metabolism modulate a range of cellular processes including proliferation, migration and apoptosis. We demonstrate that aberrations in sphingolipid metabolism occur in women with endometriosis.

METHODS:

Targeted mass spectrometry on >120 sphingolipids were measured in the sera (n = 62), peritoneal fluid (n = 63), and endometrial tissue (n = 14) of women with and without endometriosis. Quantitative RT-PCR and immunohistochemistry were performed on endometrial tissues determine the expression levels of sphingolipid enzymes.

RESULTS:

Sphingolipidomics identified the in vivo accumulation of numerous sphingolipids, including the functionally antagonistic glucosylceramides and ceramides in the serum and PF of women with endometriosis. We found upregulation of specific sphingolipid enzymes, namely sphingomyelin synthase 1 (SMS1), sphingomyelinase 3 (SMPD3), and glucosylceramide synthase (GCS) in the endometrium of endometriotic women with corresponding increased GlcCer, decreased sphingomyelin levels, and decreased apoptosis in the endometrium.

CONCLUSIONS:

Our sphingolipidomics approach provided evidence of altered sphingolipid metabolism flux in serum, peritoneal fluid, and endometrial tissue in women with endometriosis. The results provide new information on how sphingolipids and eutopic endometrium may contribute to the pathophysiology of endometriosis. The results also have implications for the use of sphingolipids as potential biomarkers.

PMID:
24960545
PMCID:
PMC5393497
DOI:
10.1210/jc.2014-1340
[Indexed for MEDLINE]
Free PMC Article

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