Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

Nutrients

Mami Miyado¹  Natsuko Kawano²  Ban Sato²  Miku Yohtsu²  Hitomi Yonezawa²  Mitsutoshi Yamada³  Daiki Katano⁴  Kenji Miyado⁴  Kuniko Tatsumi⁵  Hidekazu Saito⁵  Erika Kaneko⁵  Mitsuyoshi Amita⁵  Natsuko Naito⁵  Woojin Kang⁵  Eri Ishida⁵  Wakako Iwasaki⁵  Kae Onozawa⁵  Takakazu Saito⁵ 

[1] Department of Food and Nutrition, Beppu University, 82 Kita-Ishigaki, Beppu, Oita 874-8501, Japan;Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashi-Mita, Kawasaki, Kanagawa 214-8571, Japan;Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan;Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, Japan;Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan;

关键词: oocyte quality;    autophagy;    chloroquine;    trehalose;    lysosomal anomalies;   

DOI  :  10.3390/nu14102156

来源: DOAJ

【 摘 要 】

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.

【 授权许可】

Unknown