Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Murdoch, William J.; Gottsch, Michelle L.

doi:10.1080/03008200390151963

Cited by 38 publications

(34 citation statements)

References 97 publications

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“…Follicle rupture may be the most sensitive event, because it requires many cooperating steps to occur. Remodeling of the extracellular matrices, the cell layers in the follicle wall, and the ovarian surface epithelium at the apex of the follicle is required for follicle rupture (31,41,53). Constriction of a layer of smooth-muscle cells in the follicular wall at the time of rupture is also likely important (20).…”

Section: Discussionmentioning

confidence: 99%

Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation

Hsieh

Lee

Panigone

et al. 2007

Molecular and Cellular Biology

315

244

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In the preovulatory ovarian follicle, mammalian oocytes are maintained in prophase meiotic arrest until the luteinizing hormone (LH) surge induces reentry into the first meiotic division. Dramatic changes in the somatic cells surrounding the oocytes and in the follicular wall are also induced by LH and are necessary for ovulation. Here, we provide genetic evidence that LH-dependent transactivation of the epidermal growth factor receptor (EGFR) is indispensable for oocyte reentry into the meiotic cell cycle, for the synthesis of the extracellular matrix surrounding the oocyte that causes cumulus expansion, and for follicle rupture in vivo. Mice deficient in either amphiregulin or epiregulin, two EGFR ligands, display delayed or reduced oocyte maturation and cumulus expansion. In compound-mutant mice in which loss of one EGFR ligand is associated with decreased signaling from a hypomorphic allele of the EGFR, LH no longer signals oocyte meiotic resumption. Moreover, induction of genes involved in cumulus expansion and follicle rupture is compromised in these mice, resulting in impaired ovulation. Thus, these studies demonstrate that LH induction of epidermal growth factor-like growth factors and EGFR transactivation are essential for the regulation of a critical physiological process such as ovulation and provide new strategies for manipulation of fertility.The luteinizing hormone (LH) surge plays a central role in promoting a cascade of events in ovarian preovulatory follicles that are essential for the ovulation of a fertilizable oocyte. Acting through LH-chorionic gonadotropin (LH-CG) receptors (LHRs) (LHR is a member of the G protein-coupled receptor superfamily encoded by Lhcgr), LH induces reprogramming of the gene expression profiles of follicular somatic cells (theca and granulosa cells), changes in the secretory properties of the cumulus cells surrounding the oocyte and cumulus expansion, oocyte reentry into the meiotic cell cycle, and follicle rupture (7, 41). LHRs are highly expressed on the granulosa cells lining the antral cavity of preovulatory follicles (mural granulosa cells) and on the external theca cells that are in continuity with the surrounding stroma. However, within preovulatory follicles, oocytes and cumulus cells that are profoundly affected by the LH surge express few or no LHRs and fail to respond when directly exposed to LH in vitro (37).To explain how LH signals are propagated from the periphery toward the cumulus oocyte complex (COC), a model has been proposed whereby factors released by mural granulosa cells function in an autocrine and paracrine manner to transduce the LH effects within the follicle (34). Secretion of bioactive growth factors from the oocyte to affect somatic cells is well established (27,30); conversely, the paracrine signals originating from the somatic cells and affecting oocytes have long been sought but are largely unknown. Recently, we have proposed that intrafollicular release of members of the epidermal growth factor (EGF)-like family (34) may fulfill this ...

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Section: Discussionmentioning

confidence: 99%

Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation

Hsieh

Lee

Panigone

et al. 2007

Molecular and Cellular Biology

315

244

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“…PLANH1, the primary inhibitor of plasminogen activator that has been implicated in tumor growth and cellular remodeling (Stefansson et al 2003) and annexin a2 (ANXA2), a plasminogen-plasminogen activator co-receptor with angiogenic properties (Kim & Hajjar 2002), were also found to be differentially expressed. The upregulation of both PLANH1 and ANXA2 is curious given their contrasting functions within the plasminogen-plasminogen activator system that has functional roles in both ovulation and angiogenesis (Murdoch & Gottsch 2003). Their coexistence may simply reflect the delicate enzymatic balance that exists during cellular remodeling.…”

Section: Genbankmentioning

confidence: 99%

“…Growth factors may act directly to control follicular growth or may act indirectly by modifying the sensitivity of follicular cells to FSH and LH (Lucy 2000, Richards et al 2002a,b, Webb et al 2003, Fortune et al 2004. The release of the LH surge near the onset of estrus redirects preovulatory development and causes the biochemical differentiation of the follicle (luteinization) and ovulation (Richards et al 2002, Murdoch & Gottsch 2003. There is a shift from estrogen to progesterone synthesis, thinning and folding of the follicle wall, and dispersion of the granulosa cell layer (Smith et al 1994, Murphy et al 2001.…”

Section: Introductionmentioning

confidence: 99%

Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression

Ağca

Ries²,

Kolath³

et al. 2006

Reproduction

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The LH surge initiates the luteinization of preovulatory follicles and causes hormonal and structural changes that ultimately lead to ovulation and the formation of corpora lutea. The objective of the study was to examine gene expression in ovarian follicles (nZ11) collected from pigs (Sus scrofa domestica) approaching estrus (estrogenic preovulatory follicle; nZ6 follicles from two sows) and in ovarian follicles collected from pigs on the second day of estrus (preovulatory follicles that were luteinized but had not ovulated; nZ5 follicles from two sows). The follicular status within each follicle was confirmed by follicular fluid analyses of estradiol and progesterone ratios. Microarrays were made from expressed sequence tags that were isolated from cDNA libraries of porcine ovary. Gene expression was measured by hybridization of fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the microarray. Microarray analyses detected 107 and 43 genes whose expression was decreased or increased (respectively) during the transition from preovulatory estrogenic to -luteinized (P!0.01). Cells within preovulatory estrogenic follicles had a gene-expression profile of proliferative and metabolically active cells that were responding to oxidative stress. Cells within preovulatory luteinized follicles had a gene-expression profile of nonproliferative and migratory cells with angiogenic properties. Approximately, 40% of the discovered genes had unknown function.

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“…The MMPs are a comprehensive family of at least 28 zinc-containing endopeptidases, which can be classified into collagenases, gelatinases, stromelysins, membrane type and other MMPs by their structure, substrate specificity and subcellular distribution (Nagase & Woessner 1999, Curry & Osteen 2003. The activity of MMPs in the extracellular milieu is regulated by their tissue inhibitors (TIMPs 1-4), which bind reversibly to MMPs in a 1:1 stoichiometry and inhibit their activity (Gomez et al 1997, Brew et al 2000, Murdoch & Gottsch 2003. The PA system consists of the ubiquitous zymogen plasminogen, which can be activated to the proteolytic enzyme plasmin by two distinct forms of PA (tissue-type PA (tPA) and urokinase-type PA (uPA)) (Tsafriri & Reich 1999, Ny et al 2002.…”

Section: Introductionmentioning

confidence: 99%

Effect of intrafollicular indomethacin injection on gonadotropin surge-induced expression of select extracellular matrix degrading enzymes and their inhibitors in bovine preovulatory follicles

Li¹,

Jimenez-Krassel²,

Kobayashi³

et al. 2006

Reproduction

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A growing body of evidence supports an obligatory role for intrafollicular prostanoids in the mechanism of ovulation. However, the prostanoid-dependent mediators of the follicular extracellular matrix degradation required for ovulation are unknown. The objectives of this study were to determine the cellular compartment(s) in which the gonadotropin surgeinduced regulation of select extracellular matrix degrading enzymes and their cognate inhibitors occurs in bovine preovulatory follicles, and to test whether such regulation is blocked by intrafollicular administration of the prostanoid synthesis and ovulation inhibitor, indomethacin (INDO). Follicular fluid prostaglandin E 2 concentrations were elevated in diluenttreated follicles before ovulation (24 h after GnRH injection), but the increase was blocked in INDO-treated follicles. Realtime PCR analysis revealed the specific follicular cell types where gonadotropin surge-induced increases in mRNA abundance for members of the matrix metalloproteinase/tissue inhibitor of metalloproteinase and plasminogen activator families occurred. INDO treatment increased thecal cell mRNA for tissue inhibitor of metalloproteinase-4 and its protein abundance in the apex of preovulatory follicles before ovulation, but suppressed granulosal cell mRNA and activity for tissue plasminogen activator in follicular fluid and the follicle apex. Plasmin activity was also suppressed in the follicular fluid of INDO-treated follicles. Effects of INDO injection on select matrix metalloproteinases were not observed. The results suggest that gonadotropin surge-induced regulation of tissue inhibitor of metalloproteinase-4 and tissue plasminogen activator may be prostanoid dependent, and support a potential role for increased tissue plasminogen activator expression and decreased tissue inhibitor of metalloproteinase-4 expression in the mechanism of ovulation.

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Proteolytic Mechanisms in the Ovulatory Folliculo-Luteal Transformation

Cited by 38 publications

References 97 publications

Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation

Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation

Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression

Effect of intrafollicular indomethacin injection on gonadotropin surge-induced expression of select extracellular matrix degrading enzymes and their inhibitors in bovine preovulatory follicles

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