Mechanism of palmitic acid-induced deterioration of in vitro development of porcine oocytes and granulosa cells

• Published in: Theriogenology Vol. 141; pp. 54 - 61
• Main Authors: Shibahara, H., Ishiguro, A., Inoue, Y., Koumei, S., Kuwayama, T., Iwata, H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Animals; Apoptosis; Cell Proliferation - drug effects; Cell Survival - drug effects; Early antral follicles; Endoplasmic Reticulum; Female; Granulosa cells; Granulosa Cells - physiology; In Vitro Oocyte Maturation Techniques - veterinary; Oocyte growth; Oocytes - physiology; Palmitic acid; Palmitic Acid - toxicity; Swine; Early antral follicles; Granulosa cells; Oocyte growth; Palmitic acid
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2019.09.006

The concentration of fatty acids in follicular fluid reflect the physical condition of donors, and palmitic acid (PA) is a major component of follicular fluid. The present study examined the effect of PA on in vitro oocyte growth and investigated the molecular backgrounds of the PA induced-low quality oocytes. Oocyte-granulosa cell complexes (OGCs) were collected from early antral follicles of gilts. The OGCs were cultured for 14 days in a medium containing 0.5 mM PA or vehicle (BSA). PA was found to reduce granulosa cell (GCs) proliferation (0.73 fold) and viability (93.9% vs. 85.8%) and increase lipid content in oocytes and GCs. Oocytes developed in the presence of PA had low developmental ability to the blastocyst stage. In addition, PA affected developmental and epigenetic markers of histone modifications in oocytes; levels of H4K12 acetylation and H3K9 demethylation. PA affected cellular proliferation, apoptosis and endoplasmic reticulum stress markers along with reducing the phosphor-AKT/AKT levels and increasing the expression levels of caspase-3 and CHOP in GCs. Incubation of OGCs with PA increased ceramide content in the GC, and addition of ceramide to the culture medium inhibited GC proliferation. In conclusion, it is suggested that high PA content in the medium reduces viability and proliferation through ceramide accumulation, and PA impaires the developmental ability of oocytes grown in vitro. In addition, high-fat conditions induce changes in the histone modifications of oocytes grown in vitro. •Palmitic acid (PA) is a major component of follicular fluid. When oocyte granulomas cell complexes derived from early antral follicles of gilt ovaries were cultured with 0.5 mM of PA, granulosa cells accumulated lipid content and showed low proliferation and viability compared with those cultured with BSA control.•Oocytes developed in the presence of PA had low developmental ability and showed differential histone modifications.•This PA-induced deterioration of granulosa cells was attributed to ceramide accumulation.