scholarly journals Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition of ewes

Reproduction ◽  
2002 ◽  
pp. 347-352 ◽  
Author(s):  
ML Gottsch ◽  
EA Van Kirk ◽  
WJ Murdoch

Tissue dissolution and remodelling are associated with the processes of rupture of the ovulatory follicle and formation of the corpus luteum. Matrix metalloproteinase 2 (MMP-2) belongs to a family of endopeptidases that cleave extracellular proteins; its primary substrate is the lattice network of basement membranes that support epithelial cells and endothelium. The aim of this study was to ascertain a putative regulatory role of MMP-2 relevant to the folliculo-luteal transformation in ewes. Luteal regression and the preovulatory surge of gonadotrophins were synchronized by administration of PGF(2alpha) and GnRH on days 14.0 and 15.5 of the oestrous cycle, respectively. Dominant antral follicles present during pro-oestrus consistently ovulate approximately 24 h after GnRH administration. Normal IgG or a bioactivity-neutralizing MMP-2 monoclonal antibody was injected into the antral cavity of preovulatory follicles at 8 h after GnRH administration. Jugular blood samples were obtained for serum progesterone analysis and ovaries were removed for light microscopic morphometry on day 8. A definitive ovulation stigma was evident in control ewes. The antra of ruptured follicles had largely been supplanted with luteal tissue. In contrast, the ovarian surface contiguous with follicles injected with anti-MMP-2 was smooth and undisturbed, which is indicative of a failure of ovulation. Luteinized unruptured follicles were filled with (entrapped) fluid. Corpora lutea of control animals contained numerous connective tissue projections that provided a framework for cellular migration and angiogenesis. Luteal tissues that surrounded the cavity of antibody-treated follicles lacked trabeculae and were deficient in blood vessels. Systemic venous progesterone concentrations were lower in ewes with a luteinized unruptured follicle compared with those with a corpus luteum. It is proposed that MMP-2 is a mediator of ovulation and luteal development.

2000 ◽  
Vol 12 (2) ◽  
pp. 75 ◽  
Author(s):  
Michelle L. Gottsch ◽  
Edward A. Van Kirk ◽  
William J. Murdoch

The collagenous matrix of the wall of periovulatory follicles is degraded and remodelled during ovulatory ovarian rupture and luteinization. Matrix metalloproteinase-2 (MMP-2) belongs to a family of zinc endopeptidases that cleave extracellular proteins; its primary substrate is the type IV collagen of basement membranes. Tumour necrosis factor α (TNFα) is a putative mediator of collagenolysis and ovulation. The objective of this investigation was to ascertain the regulatory role of TNFa on MMP-2 activity relevant to the folliculo-luteal transition in ewes. Luteal regression and the preovulatory surge of gonadotropins were induced by administration of prostaglandin F 2 α and gonadotropin-releasing hormone (GnRH) on Days 14 and 15.5 (= 0 h) of the oestrous cycle, respectively. Ovulation occurs from the dominant follicle approximately 24 h after GnRH. An immunocapture-activity assay was used to measure MMP-2 in follicular extracts. Bioactive MMP-2 increased from 0 to 20 to 40 h after GnRH. Enzyme was immunolocalized at 40 h to the connective tissue framework that invades the parenchyma of the formative corpus luteum. Activity of MMP-2 was up-regulated by incubation (20 h) of 0-h follicular explants with TNFα; this response was suppressed by the transcriptional inhibitor actinomycin D. Activity of MMP-2 was reduced when preovulatory follicular tissues were incubated (12-h explants for 6 h) with TNFα antiserum. Ovulation was blocked by intrafollicular injection of TNFα antiserum. Unruptured follicles luteinized, but were deficient in collagenous/vascularized trabeculae, and produced less progesterone than their control luteal counterparts. It is suggested that TNFα, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum.


1984 ◽  
Vol 247 (6) ◽  
pp. E808-E814
Author(s):  
K. C. Yuh ◽  
C. H. Bill ◽  
P. L. Keyes

The requirement of the pituitary gland and the role of 17 beta-estradiol in the early development of the corpus luteum was investigated in rabbits hypophysectomized the day after sterile mating (day 1). Serum progesterone in hypophysectomized rabbits was normal for 2 days after hypophysectomy. Luteal tissue from hypophysectomized and sham-hypophysectomized rabbits had similar wet weight (4.0 +/- 0.4 vs. 5.3 +/- 0.2 mg/corpus luteum) and similar concentrations of available cytoplasmic estrogen receptor (1.2 +/- 0.2 vs. 1.5 +/- 0.3 fmol/micrograms DNA) and luteinizing hormone (LH) receptor (4.0 +/- 0.2 vs. 6.1 +/- 1.4 fmol/micrograms DNA) on day 4 of pseudopregnancy. Serum progesterone in hypophysectomized rabbits began to decline on day 4 and was undetectable by day 6. Estrogen receptor and luteal weight in hypophysectomized animals also declined after day 4 to low values by day 6, and serum estradiol was undetectable. However, if estradiol was administered by Silastic capsule implanted subcutaneously at the time of hypophysectomy or 3 days after hypophysectomy, serum progesterone, luteal weight, estrogen receptor, and LH receptor were maintained on day 6 of pseudopregnancy. These results indicate that after a preovulatory gonadotropin surge, the function of newly formed corpora lutea is normal for 3–4 days in the absence of pituitary hormones. However, by 4 days after ovulation, estradiol is required to sustain the structural and functional integrity of corpora lutea.


2021 ◽  
Vol 41 ◽  
pp. 100959
Author(s):  
Long-Jie Yan ◽  
Le-Chang Sun ◽  
Kai-Yuan Cao ◽  
Yu-Lei Chen ◽  
Ling-Jing Zhang ◽  
...  

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.


2018 ◽  
Vol 9 ◽  
Author(s):  
Yu Kuwabara ◽  
Tetsu Kobayashi ◽  
Corina N. D'Alessandro-Gabazza ◽  
Masaaki Toda ◽  
Taro Yasuma ◽  
...  

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009786
Author(s):  
Haili Bao ◽  
Yang Sun ◽  
Ningjie Yang ◽  
Na Deng ◽  
Zhangli Ni ◽  
...  

The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.


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