Editors' ChoiceObesity

Fatty Eggs and Infertility

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Science Translational Medicine  13 Oct 2010:
Vol. 2, Issue 53, pp. 53ec157
DOI: 10.1126/scitranslmed.3001766

It is well established that obese women have a higher prevalence of infertility and ovulatory dysfunction than nonobese women. However, the cellular mechanisms for these effects are unknown. Multiple tissues (such as the liver, skeletal muscle, and pancreas) in obese individuals have been shown to be negatively affected by “lipotoxicity”—the ectopic deposition of lipid in nonadipose tissues, which is associated with endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and apoptosis. Could this phenomenon be occurring in the ovaries of obese women as well?

Now, Wu et al. demonstrate that this is indeed the case. First, the investigators examined in a mouse model whether high-fat diet–induced obesity caused lipotoxicity in granulosa cells—hormone-producing somatic cells that are closely associated with the oocyte—and the cumulus-oocyte complex (COC). (Cumulus cells, which are derived from granulosa cells, surround the oocyte to form the COC.) Compared with oocytes of control mice, the oocytes of mice fed the high-fat diet had increased lipid content and reduced mitochondrial membrane potential, suggesting mitochondrial dysfunction. The mice fed the high-fat diet also had increased COC expression of ER stress marker genes, increased granulosa and cumulus cell apoptosis, decreased ovulation, and decreased in vivo fertilization rates. Second, the investigators evaluated ER stress markers in granulosa cells and follicular fluid from women with varying body mass indices (BMIs) and found that markers of ER stress positively correlated with BMI and that the expression of ER stress marker genes was significantly increased in granulosa cells from obese women as compared with expression in granulosa cells from moderate or overweight women.

By evaluating both mice and humans, Wu et al. identify several cellular defects that occur in the ovary and oocyte in response to obesity, supporting the role of ovarian lipotoxicity in obesity-associated infertility. Maybe a fatty egg isn’t good for a baby after all?

L. L.-Y. Wu et al., High-fat diet causes lipotoxicity responses in cumulus-oocyte complexes and decreased fertilization rates. Endocrinology 22 September 2010 (10.1210/en.2010-0551). [Abstract]

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