Dysregulated Sphingolipid Metabolism in Endometriosis

Yie Hou Lee, Chin Wen Tan, Abhishek Venkatratnam, Chuen Seng Tan, Liang Cui, Cui Liang, Seong Feei Loh, Linda G. Griffith, Linda Griffith, Steven R Tannenbaum, Jerry Kok Yen Chan
The Journal of clinical endocrinology and metabolism · 2014 · vol. 99(10) , pp. E1913–E1921 · doi:10.1210/jc.2014-1340 · PMID:24960545 · W2123076237
article OA: bronze CC0 ⤵ 45 in-corpus citations
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This study found altered sphingolipid metabolism in the serum, peritoneal fluid, and endometrium of women with endometriosis, with specific enzyme and lipid changes correlating with disease presence.

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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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Glucosyltransferases Membrane Proteins Nerve Tissue Proteins Sphingolipids Sphingomyelin Phosphodiesterase Transferases (Other Substituted Phosphate Groups) Adult Apoptosis Apoptosis Ascitic Fluid Ascitic Fluid Cell Movement Cell Movement Cell Proliferation Endometriosis Endometriosis Female Glucosyltransferases Glucosyltransferases

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (36)

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