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Disruption of gap junctional communication within the ovarian follicle induces oocyte maturation

TLDR
Because experimentally induced breakdown of communication within the ovarian follicle is associated with a drop in intraoocyte cAMP concentrations and results in resumption of meiosis, this could be the physiological mechanism employed by LH to stimulate oocyte maturation.
Abstract
Meiotically arrested mammalian oocytes are stimulated to resume meiosis by LH. This response, which can be reversed by elevation of intraoocyte cAMP levels, is associated with interruption of gap junctional communication (GJC) within the ovarian follicle. In the present study, we examined the hypothesis that disruption of GJC within the ovarian follicle is sufficient for induction of oocyte maturation. For this purpose, we incubated rat follicle-enclosed oocytes with carbenoxolone (CBX), a known blocker of gap junctions. We found that this selective disruptor of GJC promoted maturation of almost all the follicle-enclosed oocytes after 5 h of incubation; this response was also obtained by a transient (2 h) exposure to this agent. CBX-induced oocyte maturation was accompanied by a substantial decrease in intraoocyte concentrations of cAMP that was not associated with elevated activity of type 3A phosphodiesterase (PDE3A). The effect of CBX on reinitiation of meiosis was blocked by isobutylmethylxanthine, a phosphodiesterase inhibitor. Unlike LH, CBX did not activate MAPK in the follicular cells, and inhibition of the MAPK signaling pathway by means of UO126 did not prevent the resumption of meiosis. Injection of CBX into the ovarian bursa of intact animals stimulated maturation in 30% of the oocytes, whereas no maturation was observed in the contralateral ovary injected with PBS. We conclude that, because experimentally induced breakdown of communication within the ovarian follicle is associated with a drop in intraoocyte cAMP concentrations and results in resumption of meiosis, this could be the physiological mechanism employed by LH to stimulate oocyte maturation.

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Citations
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Journal ArticleDOI

The mammalian ovary from genesis to revelation

TL;DR: Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids and progestins and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics.
Journal ArticleDOI

Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte.

TL;DR: It is found that cGMP passes through gap junctions into the oocyte, where it inhibits the hydrolysis of cAMP by the phosphodiesterase PDE3A, and causes a decrease in oocyte cAMP, leading to the resumption of meiosis.
Journal ArticleDOI

Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization

TL;DR: The importance of oocyte maturation for the achievement of female meiosis has long been recognized, but until recently much less was known of the significance of this process in relation to other fundamental developmental events.
Journal ArticleDOI

Molecular control of oogenesis.

TL;DR: Recent knowledge on the molecular aspects of oogenesis and oocyte maturation, and the crucial role of cumulus-cell interactions are summarized, highlighting the valuable contribution of experimental evidences obtained in animal models.
Journal ArticleDOI

Novel signaling mechanisms in the ovary during oocyte maturation and ovulation

TL;DR: This review will provide a summary of the current knowledge of the molecular events triggered by LH focusing mostly on the signaling pathways required for oocyte maturation.
References
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Journal ArticleDOI

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TL;DR: Six new phosphodiesterase genes have been discovered and characterized, and new strategies have been employed to determine PDE function in model systems including the use of antisense oligonucleotide and disruption techniques.
Journal ArticleDOI

The mammalian ovary from genesis to revelation

TL;DR: Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids and progestins and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics.
Journal ArticleDOI

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TL;DR: Tracer and freeze-fracture electron microscopy of the ovaries of neonatal rat and adult mouse, rat, rabbit, and primate have revealed the presence of gap junctions between follicle cells and oocytes.
Journal ArticleDOI

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TL;DR: Since connexin43 (Cx43) is widely expressed in tissues and cell lines, it is understood the most about how it is regulated, and thus, con Nexin43 phosphorylation is a major focus of this review.
Journal ArticleDOI

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TL;DR: Cell communication is a characterisitc feature of the cumulus-oocyte complex, and this communication is terminated near the time of ovulation, which may indicate that communication provides a mechanism for regulating the maturation of the oocyte during follicular development before ovulation.
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