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Spatiotemporal Crosstalk Between Oocyte and the Microenvironment Governs Preovulatory Follicle Aging
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Spatiotemporal Crosstalk Between Oocyte and the Microenvironment Governs Preovulatory Follicle Aging
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Journal Article
Spatiotemporal Crosstalk Between Oocyte and the Microenvironment Governs Preovulatory Follicle Aging
2026
Overview
Preovulatory follicle aging is the period between formation and ovulation of a mature follicle. Previous studies had shown that mammalian preovulatory follicle aging is associated with chromosomal abnormalities and developmental defects such as decreased implantation, increased malformation and mortality and lower embryonic weight. Our understanding of the molecular events governing this process has been hampered by the difficulty in accessing them in vivo under natural conditions. We hypothesize that the quality of the mature oocyte is regulated by crosstalk between the oocyte and the somatic microenvironment during extended storage prior to ovulation. By combining temporal profiling and tissue‐specific functional analyzes in Drosophila, we characterize a spatiotemporal crosstalk between the oocyte and the granulosa cells that governs preovulatory follicle aging in vivo. Preovulatory follicle aging is characterized by two distinct phases—early oocyte protective and late degenerative phases. The degenerative phase involves a positive feedback loop between oocyte mitochondrial dysfunction mediated by a mitochondrial‐localized microprotein PIGBOS, and granulosa cell functional decline through a circular RNA circdlg1. Activation of the feedback loop is suppressed by germline Sestrin during the early phase. Our findings highlight that natural preovulatory follicle aging in vivo is governed by a mechanism that represses an oocyte‐degenerative positive feedback loop between oocyte and granulosa cells. Preovulatory follicle aging is characterized by two distinct phases—early oocyte protective and late degenerative phases. The degenerative phase involves a positive feedback loop between oocyte mitochondrial dysfunction mediated by a mitochondrial‐localized microprotein PIGBOS, and granulosa cell functional decline through a circular RNA circdlg1. Activation of the feedback loop is suppressed by germline Sestrin during the early phase. Thus, preovulatory follicle aging is governed by a mechanism that represses an oocyte‐degenerative positive feedback loop between oocyte and granulosa cells.
