Lipid droplets in granulosa cells are correlated with reduced pregnancy rates

Abstract

Background: Lipids are an important source for energy production during oocyte maturation. The accumulation of intracellular lipids binds to proteins to form lipid droplets. This may lead to cellular lipotoxicity. The impact of lipotoxicity on cumulus and granulosa cells has been reported. This pilot study evaluated their correlation to oocyte and embryo quality. Design: Prospective case-control study. Setting: Referral IVF unit. Patients: Women younger than age 40, undergoing IVF with intracytoplasmic sperm injection. Interventions: 15 women with BMI > 30 (high BMI) and 26 women with BMI < 25 (low BMI) were enrolled. IVF outcomes were compared between groups based on BMI. Lipid content in cumulus and granulosa cells was evaluated using quantitative and descriptive methods. Lipid profile, hormonal profile and C-reactive protein were evaluated in blood and follicular fluid samples. Demographic and treatment data, as well as pregnancy rates were collected from electronic medical records. Results: Higher levels of LDL and CRP, slower cell division rate and lower embryo quality were found in the group with high BMI. There was no difference in pregnancy rates between groups. In light of these findings, treatment outcomes were reanalyzed according to patients who became pregnant and those who did not. We found that patients who conceived had significantly lower fat content in the granulosa cells, reflected by mean fluorescence intensity recorded by flow cytometry analysis (23,404 vs. 9370, P = 0.03). Conclusions: BMI has no effect on lipid content in cumulus and granulosa cells, and does not affect likelihood of pregnancy. However, women who achieved pregnancy, regardless of their BMI, had lower lipid levels in their granulosa cells. This finding is important and further study is needed to evaluate lipid content in granulosa cells as a potential predictor of IVF treatment success.

Genome wide effects of oleic acid on cultured bovine granulosa cells: evidence for the activation of pathways favoring folliculo-luteal transition

“…This is also supported by the observation of morphological changes in OA treated GCs showing lipid droplet accumulation. Also in human lipid droplet accumulation in GCs have been correlated with fertility problems [ 24 ]. Also recent in vivo data suggest that increased NEFA levels and in particular increased OA concentrations in the follicular fluid have detrimental effects on follicle growth and even prevent ovulation [ 18 , 25 ].…”

Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development

“…Mediating the uptake of LDL by ovarian follicle cells, LDLR was downregulated in PCOS granulosa cells, which is consistent with previous studies ( 37 , 38 ). In addition, lipid content in granulosa and cumulus cells may affect likelihood of pregnancy, loss of function of LDLR resulted in impaired lipid uptake and extracellular lipid accumulation, thus leading to hyperlipidemia and poor fertility in mice ( 39 ). Overall, our results showed that abnormal lipid metabolism and fatty acid synthetic pathways were closely related to the development of PCOS, while the specific mechanism underlying how these metabolic disorders contributed to ovulatory disorders in PCOS remains elusive.…”

Dyslipidemia Is Negatively Associated With the Cumulative Live-Birth Rate in Patients Without PCOS Following IVF/ICSI

“…Moreover, a recent study found that the patients with accumulation of lipid droplets in cumulus and granulosa cells had lower IVF/ICSI pregnancy rates, regardless of their BMI (Raviv et al, 2020). Excess fatty acids could damage the cumulus and granulosa cells, which are the major functional cells of the female gonads thus impairing their ability to perform normal steroidogenesis (Raviv et al, 2020). High dietary fat intake, with or without the development of obesity, impairs female hypothalamic-pituitary-ovarian (HPO) axis as well as fertility (Hohos and Skaznik-Wikiel, 2017).…”