Signaling modalities during oogenesis in mammals

Abstract

During oogenesis in mammals, the germ line interacts with ovarian somatic cells as follicles assemble, grow, ovulate, and die. As a result, these interactions with granulosa cells determine germ cell fate as the oocyte undergoes hypertrophy, the final stages of meiosis, and preparations required for successful fertilization. Over the past 15 years, investigators using a range of experimental approaches have uncovered the existence of multiple modalities for signaling between the oocyte and companion granulosa cells that play essential and sometimes overlapping roles during the growth and maturative phases of oogenesis. Five modalities of intercellular signaling are considered in the context of regulating oocyte gene expression, metabolism, spatial patterning, and the cell cycle. While some forms of signaling predominate at specific stages of oogenesis, such as during the assembly of primordial follicles, it is apparent that combinations of modalities work in concert to control events associated with ovulation when both nuclear and cytoplasmic maturation occur. A final key feature of the signaling platform underscoring the protracted process of oogenesis is the existence of negative and positive feedback loops designed to coordinate the tempo of oogenesis and folliculogenesis at key developmental transitions.