Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes

Kawamura, Kazuhiro; Cheng, Yuan; Kawamura, Nanami; Takae, Seido; Okada, Aya; Kawagoe, Yuta; Mulders, S.M.; Terada, Yukihiro; Hsueh, Aaron J. W.

doi:10.1093/humrep/der282

Cited by 134 publications

(166 citation statements)

References 24 publications

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“…Treatment of isolated COCs with NPPC promotes elevation of cGMP levels (12,26). Moreover, mutations in either the Npr2 or Nppc genes in mice result in failure to maintain meiotic arrest and precocious resumption of meiosis (12,27,28).…”

Section: Significancementioning

confidence: 99%

Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes

Wigglesworth

Lee

O’Brien

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

173

132

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Coordinated regulation of oocyte and ovarian follicular development is essential for fertility. In particular, the progression of meiosis, a germ cell-specific cell division that reduces the number of chromosomes from diploid to haploid, must be arrested until just before ovulation. Follicular somatic cells are well-known to impose this arrest, which is essential for oocyte-follicle developmental synchrony. Follicular somatic cells sustain meiotic arrest via the natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/ NPR2) system, and possibly also via high levels of the purine hypoxanthine in the follicular fluid. Upon activation by the ligand NPPC, NPR2, the predominant guanylyl cyclase in follicular somatic cells, produces cyclic guanosine monophosphate (cGMP), which maintains meiotic arrest after transfer to the oocyte via gap junctions. Here we report that both the NPPC/NPR2 system and hypoxanthine require the activity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme required for the production of guanylyl metabolites and cGMP. Furthermore, oocyte-derived paracrine factors, particularly the growth differentiation factor 9-bone morphogenetic protein 15 heterodimer, promote expression of Impdh and Npr2 and elevate cGMP levels in cumulus cells. Thus, although the somatic compartment of ovarian follicles plays an essential role in the maintenance of oocyte meiotic arrest, as has been known for many years, this function of the somatic cells is surprisingly regulated by signals from the oocyte itself. F ertility in mammals depends on the coordinated development of ovarian follicles and the oocytes contained within them. The ovulation of oocytes by Graafian follicles must coincide with oocyte meiotic progression. Meiosis is a germ cell-specific cell division that reduces the number of chromosomes from diploid to haploid. In mammals, oocytes are arrested at the diplotene stage (diploid) of meiosis until the surge of luteinizing hormone (LH) from the pituitary gland initiates the ovulatory process. The LH surge initiates the resumption of meiosis and its progression to the metaphase of the second meiotic division, and these haploid oocytes (eggs) are ovulated into the oviduct to await fertilization. Ever since the classic experiments of Pincus and Enzmann (1) in the 1930s, it has been widely accepted that follicular somatic cells of Graafian follicles maintain the fully grown oocytes in meiotic arrest until the LH surge: Removing them from follicles for culture in a supportive medium before the surge results in an LH-independent resumption of meiosis. Thus, isolated oocytes resume meiosis simply because they have been separated from the inhibitory effect of follicular somatic cells. The mechanisms by which these cells maintain oocyte meiotic arrest have been the subject of numerous studies over the last 75 y.Oocytes arrested at the diplotene stage are referred to as germinal vesicle (GV)-stage oocytes, and the dissolution of the oocyte nuclear envelope, often referred to as germinal vesic...

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Section: Significancementioning

confidence: 99%

Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes

Wigglesworth

Lee

O’Brien

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

173

132

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“…LH acts by lowering the levels of cGMP in the granulosa cells, thus reducing cGMP in the oocyte. Although this regulatory system is best understood in mice (Norris et al, 2009;Vaccari et al, 2009;Zhang et al, 2010;Kawamura et al, 2011;Tsuji et al, 2012;Geister et al, 2013), there is evidence that similar mechanisms operate in other mammals (Törnell et al, 1991;Peng et al, 2013;Hiradate et al, 2014;Zhang et al, 2014), including women (Kawamura et al, 2011;Liu et al, 2014). The LH-induced resumption of the meiotic cell cycle leads into a series of events by which the oocyte matures to become a fertilizable egg (Conti et al, 2012;Clift and Schuh, 2013;Holt et al, 2013;Mehlmann, 2013;Hunzicker-Dunn and Mayo, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…cGMP is produced in the granulosa cells of mice by natriuretic peptide receptor 2 (NPR2), also known as guanylyl cyclase-B (Zhang et al, 2010;Kawamura et al, 2011;Tsuji et al, 2012;Geister et al, 2013). NPR2 appears to be the only relevant guanylyl cyclase in mouse follicles because follicle-enclosed oocytes in the ovaries of mice with non-functional NPR2 resume meiosis spontaneously (Zhang et al, 2010;Tsuji et al, 2012;Geister et al, 2013) and an inactivating mutation in NPR2 reduces the cGMP content of the follicle to an undetectable level (Geister et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…LH signaling is known to decrease the amount of CNP in rat and mouse ovaries (Jankowski et al, 1997;Kawamura et al, 2011;Liu et al, 2014) and in human and porcine follicular fluid (Kawamura et al, 2011;Zhang et al, 2014); the decrease in the levels of CNP is associated with a decrease in Nppc mRNA (Kawamura et al, 2011;Tsuji et al, 2012;Liu et al, 2014). However, in the mouse ovary, where the kinetics are best characterized, the CNP decrease is first detected at 2 h Liu et al, 2014), whereas the decrease in cGMP is detected at 15 to 20 min (Norris et al, 2010;Liu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

et al. 2014

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In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte.

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“…Later studies demonstrated that NPPC is expressed by bovine cumulus cells, and that, like in the mouse, NPPC also inhibits germinal vesicle breakdown (GVBD) in cattle De Cesaro et al, 2015). For meiosis resumption to occur, LH inhibits NPPC production by granulosa cells and reduces the flow of cGMP from the outer layers of the cumulus to the oocyte (Kawamura et al, 2011;Shuhaibar et al, 2015). Reduced gap junction functionality after the LH surge is believed to be a consequence of the production/secretion of EGF-like peptides that bind to the EGFR to induce mitogen activated protein kinase (MAPK) dependent phosphorylation of connexins, the main components of gap junctions (Conti et al, 2012).…”

Section: Oocyte and Cumulus-derived Factors In The Regulation Of Nuclmentioning

confidence: 99%

Follicular environment and oocyte maturation: roles of local peptides and steroids

Buratini¹,

Soares²,

Barros³

2017

Anim Reprod

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A large amount of data on the mechanisms regulating cumulus-oocyte maturation in mammals has been generated in the last 20 years. It has been made clear that oocyte-secreted factors play a central role in the control of cumulus differentiation and oocyte developmental competence. However, more recent data indicate that cumulus-derived factors are also involved. In this mini-review, we have compiled and discussed data produced in our laboratory about the involvement of oocyte and cumulus-derived peptides, including fibroblast growth factors, bone morphogenetic protein 15, Kit ligand and natriuretic peptide C, in the regulation of cumulus metabolism and oocyte nuclear maturation. In addition, we discuss the interaction of follicular steroids with natriuretic peptide C in the control of meiosis progression.

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Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes

Abstract: Our findings demonstrate gonadotrophins regulation of NPPC/CNP expression in mouse and human ovaries and confirm the role of CNP as a potent paracrine oocyte maturation inhibitor.

Cited by 134 publications

References 24 publications

Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes

Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes

Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

Follicular environment and oocyte maturation: roles of local peptides and steroids

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