Metalloproteases in gonad formation and ovulation

Zhu, Yong

doi:10.1016/j.ygcen.2021.113924

Cited by 16 publications

(11 citation statements)

References 223 publications

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“…Activation of multiple metalloproteases within the ovulating follicles at the right times is a critical step for sequential digestion of extracellular matrix proteins of the follicular cells that are required for ovulation (1,42). Their activation and substrate binding are precisely regulated by the timing of prodomain cleavage of the enzyme and removal of endogenous tissue inhibitors of metalloproteases (Timps) (63). Protease inhibitors (Timps and other inhibitors) are typically present at high concentrations in the serum to prevent metalloproteases from acting accidentally (64, left side of Fig.11).…”

Section: Discussionmentioning

confidence: 99%

Nuclear Progestin Receptor Mediated Linkage of Blood Coagulation and Ovulation

Huang

Chao

Zhao

et al. 2021

Preprint

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Ovulation is a remodeling process including blood capillary rupture and coagulation. Until now, there is no regulation and functional studies of coagulation factors in ovulation. Here, we report dramatic increases of coagulation factors (f5, f3a) in zebrafish preovulatory follicles. This upregulation was induced by progestin (DHP: 17α, 20β-dihydroxy-4-pregnen-3-one), a native ligand for nuclear progestin receptor (Pgr) that is essential for ovulation in zebrafish; but was abolished in pgr-/-. In addition, promoter activities of f5 and f3a were significantly enhanced by progestin via zebrafish Pgr. Similarly, we found promoter activities of human F5 were significantly stimulated by progesterone (P4) via human PGRB. Moreover, a dramatic increase of erythrocyte numbers in capillaries on ovarian follicles was associated with ovulation. Importantly, heparin, an anticoagulant, inhibited ovulation. Furthermore, reduced fecundity and impaired ovulation were observed in f5+/- female zebrafish. Together, our results provide plausible evidence for an exceptional function of coagulation factors in ovulation.Significance StatementPrecise activation of metalloprotease is essential for ovulation. This activation is controlled by serum-derived protease inhibitors. However, the association between coagulation factors and ovulation is unclear. We demonstrated that nuclear progestin receptor (Pgr), a well-established initiator for ovulation, was a major regulator for a dramatic increase of coagulation factors (f5 & f3a) in preovulatory follicles of zebrafish. Blood coagulation in the capillaries of preovulatory follicles occurred prior to follicular rupture in wildtype zebrafish. Interestingly, this blood coagulation was blocked in Pgr knockout fish, which can’t ovulate. Inhibition of blood coagulation significantly reduced ovulation. Decreased fertility was also found in F5 heterozygous zebrafish. Our findings reveal critical roles of steroid receptor-regulated coagulation factors in blood coagulation that controls ovulation.

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Section: Discussionmentioning

confidence: 99%

Nuclear Progestin Receptor Mediated Linkage of Blood Coagulation and Ovulation

Huang

Chao

Zhao

et al. 2021

Preprint

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Section: Discussionmentioning

confidence: 99%

Nuclear Progestin Receptor–mediated Linkage of Blood Coagulation and Ovulation

et al. 2022

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Ovulation is a dramatic remodeling process that includes rupture of blood capillaries and clotting, but coagulation is not thought to directly regulate this process. Herein, we report remarkable increases of coagulation factors V (f5, ~3145-fold) and tissue factor (f3a, ~120-fold) in zebrafish ovarian follicle cells during ovulation. This increase was mediated through the nuclear progestin receptor (Pgr), which is essential for ovulation in zebrafish, and was totally abolished in ovarian follicular cells from pgr-/- mutants. In addition, promoter activities of f5 and f3a were significantly enhanced by progestin (DHP) via Pgr. Similar regulation of human F5 promoter activity was induced via human PGRB, suggesting a conserved mechanism. Site-directed mutagenesis of the zebrafish f5 promoter further demonstrated a direct regulation of coagulation factors via progestin response elements. Moreover, a stark increase of erythrocytes occurred in capillaries meshed in wildtype preovulatory follicles but was absent in pgr-/- mutants. Interestingly, anticoagulants significantly inhibited ovulation both in vitro and in vivo, respectively. Furthermore, reduced fecundity was observed in f5+/- female zebrafish. Taken together, our study provides plausible evidence for steroid regulation of coagulation factors, and a new hypothesis for blood clotting triggered ovulation in vertebrates.

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“…A disintegrin and metalloproteinase (ADAM) family and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, which are closely related to the MMP gene family, have also been reported to be involved in ovulation in vertebrates [ 47 ]. In mice, adam8 expression is induced in granulosa and cumulus cells by the combination of the LH and nuclear progestin receptor (nPR or Pgr) in preovulatory follicles [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Ovulation-Related Gene Expression during Induced Ovulation in the Amur Sturgeon (Acipenser schrenckii) Ovarian Follicles

Surugaya

Hasegawa

Adachi

et al. 2022

IJMS

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The luteinizing hormone (LH) and maturation-inducing steroids (MIS), such as 17α,20β-dihydroxy-4-pregnen-3-one, regulate the final oocyte maturation in teleosts. Oocyte maturational competence (OMC) and ovulatory competence measure the sensitivity to MIS for oocyte maturation and ovulation, respectively. However, the molecular mechanisms underlying the acquisition of ovulatory competence remain unknown. Sturgeons are an excellent research model for investigating these mechanisms. We examined the seasonal profiles of OMC and ovulatory competence in vitro and the expression of 17 ovulation-related gene candidates using quantitative PCR in Amur sturgeon ovarian follicles. The ovulatory competence was induced by the LH-releasing hormone analog (LHRHa) priming injection after acquiring the OMC, which was spontaneously induced in spring or autumn. Seven genes, including the tissue-type plasminogen activator (plat), were enhanced following the LHRHa priming injection in ovarian follicles sampled from anovulated and ovulated fish. The activin receptor type 1 (acvr1) and prostaglandin G/H synthase 2 (ptgs2) were only upregulated in ovulated fish. Our results suggest that plat/plasmin and prostaglandin (PG)/PG receptor systems are essential for sturgeon ovulation, similar to other vertebrates. Notably, successful ovulation depends on a sufficient PG synthesis, and mediators activating the PG/PG receptor system are essential for acquiring the ovulatory competence. We provide the first report of ovulation-related gene alterations in the ovarian follicles of Amur sturgeons.

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Metalloproteases in gonad formation and ovulation

Cited by 16 publications

References 223 publications

Nuclear Progestin Receptor Mediated Linkage of Blood Coagulation and Ovulation

Nuclear Progestin Receptor Mediated Linkage of Blood Coagulation and Ovulation

Nuclear Progestin Receptor–mediated Linkage of Blood Coagulation and Ovulation

Changes in Ovulation-Related Gene Expression during Induced Ovulation in the Amur Sturgeon (Acipenser schrenckii) Ovarian Follicles

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