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

Woojin Kang, Eri Ishida, Mitsuyoshi Amita, Kuniko Tatsumi, Hitomi Yonezawa, Miku Yohtsu, Daiki Katano, Kae Onozawa, Erika Kaneko, Wakako Iwasaki, Natsuko Naito, Mitsutoshi Yamada, Natsuko Kawano, Mami Miyado, Ban Sato, Hidekazu Saito, Takakazu Saito, Kenji Miyado

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2156
JournalNutrients
Volume14
Issue number10
DOIs
Publication statusPublished - 2022 May 1

Keywords

  • autophagy
  • chloroquine
  • lysosomal anomalies
  • oocyte quality
  • trehalose

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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