Filopodia-like protrusions of adjacent somatic cells shape the developmental potential of oocytes

Abstract

The oocyte must grow and mature before fertilization, thanks to a close dialogue with the somatic cells that surround it. Part of this communication is through filopodia-like protrusions, called transzonal projections (TZPs), sent by the somatic cells to the oocyte membrane. To investigate the contribution of TZPs to oocyte quality, we impaired their structure by generating a full knockout mouse of the TZP structural component myosin-X (MYO10). Using spinning disk and super-resolution microscopy combined with a machine-learning approach to phenotype oocyte morphology, we show that the lack ofMyo10decreases TZP density during oocyte growth. Reduction in TZPs does not prevent oocyte growth but impairs oocyte-matrix integrity. Importantly, we reveal by transcriptomic analysis that gene expression is altered in TZP-deprived oocytes and that oocyte maturation and subsequent early embryonic development are partially affected, effectively reducing mouse fertility. We propose that TZPs play a role in the structural integrity of the germline–somatic complex, which is essential for regulating gene expression in the oocyte and thus its developmental potential.

SMAD4 promotes somatic-germline contact during murine oocyte growth

“…New TZPs are generated throughout follicular growth, thereby increasing intercellular molecular trafficking (El-Hayek et al, 2018a). A genetically imposed decrease in the number of TZPs leads to defects in oocyte gene expression and to abnormal meiotic maturation and embryonic development (Crozet et al, 2023). Despite the essential role of TZPs during oocyte development in mammals, as well as the presence of analogous structures in non-mammalian species (Kessel et al, 1985, Schroeder, 1981, the molecular mechanisms that govern their generation and stability are not yet understood.…”

“…The TGFβ signalling pathway regulates the functions and interactions of a wide range of cell types under various physiological and pathological conditions (Derynck andBudi, 2019, Peng et al, 2022). Binding of the ligand to a complex of type I and type II receptors located at the cell surface activates signalling within the cell, most commonly through the members of the SMAD family of transcription factors, although SMAD-independent signaling can also occur (Aashaq et al, 2022, Derynck andBudi, 2019).…”

“…The TGFβ signalling pathway regulates the functions and interactions of a wide range of cell types under various physiological and pathological conditions (Derynck andBudi, 2019, Peng et al, 2022). Binding of the ligand to a complex of type I and type II receptors located at the cell surface activates signalling within the cell, most commonly through the members of the SMAD family of transcription factors, although SMAD-independent signaling can also occur (Aashaq et al, 2022, Derynck andBudi, 2019). Upon phosphorylation of the tetrameric type II and type I receptors and subsequent phosphorylation of receptor-activated SMAD proteins (R-SMADs; SMAD1, 2, 3, 5 and 8), a heterotrimeric complex with SMAD4 is formed which enters the nucleus and regulates gene expression by binding to specific SMADbinding DNA elements.…”

“…The tips of the TZPs establish contact with the oocyte plasma membrane through heterotypic adherens junctions comprising N-cadherin (granulosa cell) and E-cadherin (oocyte) and harbour the gap junctions that link the two cell types (Mora et al, 2012) and likely also through focal adhesions (McGinnis & Kinsey, 2015). New TZPs are generated throughout follicular growth, thereby increasing intercellular molecular trafficking (El-Hayek et al, 2018a), and a genetically imposed decrease in the number of TZPs is associated with defects in oocyte gene expression and development (Crozet et al, 2023). Despite the essential role of TZPs during oocyte development in mammals and the presence of analogous structures in the ovarian follicles of non-mammalian species (Kessel et al, 1985;Schroeder, 1981), the molecular mechanisms that govern their generation and stability are little understood.…”

Superovulation and aging perturb oocyte-granulosa cell communication

“…However, the oocyte can only mature if it establishes correct bi-directional communication with the surrounding cumulus granulosa cells. [49][50][51][52][53][54] To better understand the developmental potential linked to the initial oocyte quality, a close investigation of ovulated COC is necessary. However, previous efforts to separate individual oocytes and granulosa cells were limited to post-mortem surgical extraction of immature cells from the ovary in mice, 55,56 cows, 57 monkeys, 58 and humans.…”