Exposure to lipid-rich follicular fluid is associated with endoplasmic reticulum stress and impaired oocyte maturation in cumulus-oocyte complexes

Capsule:
Oocytes matured in lipid-rich follicular fluid from obese women exhibit increased oocyte lipid content, induction of endoplasmic reticulum stress genes, and impaired nuclear maturation.

Authors:
Xing Yang, M.D., Ph.D., Linda L. Wu, Ph.D., Lindsay R. Chura, Xiaoyan Liang, M.D., Michelle Lane, Ph.D., Robert J. Norman, M.D., Rebecca L. Robker, Ph.D.
Volume 97, Issue 6 , Pages 1438-1443, June 2012

Objective:
To determine whether the high lipid content of human follicular fluid influences oocyte maturation.

Design:
Mouse oocytes as substitutes for human oocytes were exposed to follicular fluids of differing lipid content with outcome monitoring.

Setting:
Private infertility clinic and university laboratory.

Patient(s):
Seventy-four women seeking assisted reproduction, and gonadotropin-stimulated mice.

Intervention(s):
Assay of follicular fluids for triglyceride and free fatty acids, and stimulation of mouse cumulus-oocyte complexes (COCs) to maturity in vitro in the presence of lipid-rich or lipid-poor follicular fluid.

Main Outcome Measure(s):
Oocyte lipid content, expression of endoplasmic reticulum stress marker genes, and oocyte maturation assessed in mouse COCs exposed to lipid-rich follicular fluid were compared with complexes exposed to lipid-poor follicular fluid and complexes matured in vivo.

Result(s):
Follicular fluids were obtained from women of known body mass index undergoing oocyte aspiration at a private infertility clinic, and the follicular fluids were assayed for triglyceride and free fatty acids; those with the highest and lowest levels of these lipids were selected. The mouse COCs exposed to lipid-rich follicular fluid during their maturation had increased oocyte lipid content, induction of endoplasmic reticulum stress markers, and impaired oocyte nuclear maturation.

Conclusion(s):
Increased body mass index is associated with elevated triglycerides and free fatty acids in ovarian follicular fluid. Maturation within this lipid-rich environment is detrimental to oocytes.

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