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Dynamin 2-dependent endocytosis is essential for mouse oocyte development and fertility

Journal Article


Abstract


  • During folliculogenesis, oocytes are dependent on metabolic and molecular support from surrounding somatic cells. Here, we examined the role of the dynamin (DNM) family of mechanoenzymes in mediating endocytotic uptake into growing follicular oocytes. We found DNM1 and DNM2 to be highly expressed in growing follicular oocytes as well as in mature germinal vesicle (GV) and metaphase II (MII) stage oocytes. Moreover, oocyte-specific conditional knockout (cKO) of DNM2 (DNM2Δ) led to complete sterility, with follicles arresting at the preantral stage of development. In addition, DNM2Δ ovaries were characterized by disrupted follicular growth as well as oocyte and follicle apoptosis. Further, the loss of DNM activity, either through DNM2 cKO or through pharmacological inhibition (Dyngo 6a) led to the impairment of endocytotic pathways in preantral oocytes as well as in mature GV and MII oocytes, respectively. Loss of DNM activity resulted in the redistribution of endosomes and the misslocalization of clathrin and actin, suggesting dysfunctional endocytosis. Notably, there was no observable effect on the fertility of DNM1Δ females. Our study has provided new insight into the complex and dynamic nature of oocyte growth during folliculogenesis, suggesting a role for DNM2 in mediating the endocytotic events that are essential for oocyte development.

Publication Date


  • 2020

Citation


  • Mihalas, B. P., Redgrove, K. A., Bernstein, I. R., Robertson, M. J., McCluskey, A., Nixon, B., . . . Sutherland, J. M. (2020). Dynamin 2-dependent endocytosis is essential for mouse oocyte development and fertility. FASEB Journal, 34(4), 5162-5177. doi:10.1096/fj.201902184R

Scopus Eid


  • 2-s2.0-85079702770

Start Page


  • 5162

End Page


  • 5177

Volume


  • 34

Issue


  • 4

Abstract


  • During folliculogenesis, oocytes are dependent on metabolic and molecular support from surrounding somatic cells. Here, we examined the role of the dynamin (DNM) family of mechanoenzymes in mediating endocytotic uptake into growing follicular oocytes. We found DNM1 and DNM2 to be highly expressed in growing follicular oocytes as well as in mature germinal vesicle (GV) and metaphase II (MII) stage oocytes. Moreover, oocyte-specific conditional knockout (cKO) of DNM2 (DNM2Δ) led to complete sterility, with follicles arresting at the preantral stage of development. In addition, DNM2Δ ovaries were characterized by disrupted follicular growth as well as oocyte and follicle apoptosis. Further, the loss of DNM activity, either through DNM2 cKO or through pharmacological inhibition (Dyngo 6a) led to the impairment of endocytotic pathways in preantral oocytes as well as in mature GV and MII oocytes, respectively. Loss of DNM activity resulted in the redistribution of endosomes and the misslocalization of clathrin and actin, suggesting dysfunctional endocytosis. Notably, there was no observable effect on the fertility of DNM1Δ females. Our study has provided new insight into the complex and dynamic nature of oocyte growth during folliculogenesis, suggesting a role for DNM2 in mediating the endocytotic events that are essential for oocyte development.

Publication Date


  • 2020

Citation


  • Mihalas, B. P., Redgrove, K. A., Bernstein, I. R., Robertson, M. J., McCluskey, A., Nixon, B., . . . Sutherland, J. M. (2020). Dynamin 2-dependent endocytosis is essential for mouse oocyte development and fertility. FASEB Journal, 34(4), 5162-5177. doi:10.1096/fj.201902184R

Scopus Eid


  • 2-s2.0-85079702770

Start Page


  • 5162

End Page


  • 5177

Volume


  • 34

Issue


  • 4