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Br J Pharmacol. 2014 Feb;171(4):827-36. doi: 10.1111/bph.12311.

Midkine and cytoplasmic maturation of mammalian oocytes in the context of ovarian follicle physiology.

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Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.


Midkine (MK) was originally characterized as a member of a distinct family of neurotrophic factors functioning in the CNS. However, it was later discovered that MK is abundantly expressed in ovarian follicles. Since then, the physiological roles of this molecule in the ovary have been steadily investigated. During the in vitro maturation (IVM) of oocytes MK was shown to promote the cytoplasmic maturation of oocytes, as indicated by post-fertilization development. This effect of MK could be mediated via its pro-survival (anti-apoptotic) effects on the cumulus-granulosa cells that surround oocytes. The oocyte competence-promoting effects of MK are discussed in the context of the recently discovered involvement of MK in the full maturation of ovarian follicles. MK was at the frontline of a new paradigm for neurotrophic factors as oocytetrophic factors. MK may promote the developmental competence of oocytes via common signalling molecules with the other neurotrophic factor(s). Alternatively or concomitantly, MK may also interact with various transmembrane molecules on cumulus-granulosa cells, which are important for ovarian follicle growth, dominance and differentiation, and act as a unique pro-survival factor in ovarian follicles, such that MK promotes oocyte competence. MK, along with other ovarian neurotrophic factors, may contribute to the optimization of the IVM system.


This article is part of a themed section on Midkine. To view the other articles in this section visit


cumulus cell; cytoplasmic maturation; developmental competence; follicle; granulosa cell; in vitro maturation; midkine; oocyte maturation; ovary

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