Nitric oxide induces gelatinase A (matrix metalloproteinase 2) during rat embryo implantation

Novaro, Virginia; Pustovrh, María Carolina; Colman‐Lerner, Alejandro; Radisky, Derek C.; Nostro, Fabiana Laura Lo; Paz, Dante A.; Jawerbaum, Alicia; González, Ezequiel

doi:10.1016/s0015-0282(02)04240-1

Cited by 38 publications

(38 citation statements)

References 42 publications

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“…(30,31), we think that, if comprised in a physiological range, increased NO may act at different sites to promote implantation. It could contribute to embryonic implantation by increasing: endometrial vascular permeability; prostaglandin mediated decidualization; programmed cell death; extracellular matrix degradation; and uterine relaxation (2,3,32,33).…”

Section: Discussionmentioning

confidence: 99%

Embryonic Production of Nitric Oxide and Its Role in Implantation: A Pilot Study

Battaglia

Ciotti

Notarangelo

et al. 2003

J Assist Reprod Genet

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Purpose : To investigate the ability of human embryos to produce nitric oxide (NO) and correlate its production with embryo quality and pregnancy rate. Methods : Twenty-three women participated in the study and were submitted to controlled ovarian stimulation and intracytoplasmic sperm injection. Embryos were singularly cultured in medium microdrops of 50 µL and were replaced, by transcervical transfer, at the 2-to 6-cell stage. In the culture media of each embryo the NO production was assessed by monitoring the levels of its stable oxidation products (nitrites/nitrates). Results : All the 23 patients underwent embryo transfer. After microinjection 64 embryos were obtained. The mean number of transferred embryos was 2.61 ± 0.46 and the pregnancy rate was 26%. The mean nitrite/nitrate concentrations of culture medium of each embryo was significantly higher (5.88 ± 2.34 µmol/L) than in pure P-1 medium (0.81 ± 0.21 µmol/L; p < 0.001) demonstrating an embryonic secretion of NO. Comparing pregnant (7.34 ± 2.72 µmol/L) versus nonpregnant patients (5.53 ± 1.49 µmol/L; p = 0.022), the mean nitrite/nitrate concentrations were significantly higher. Furthermore, the best quality embryos of pregnant women produced significantly higher nitrite/nitrate concentrations than those of not pregnant patients. Conclusions : It seems that NO production in nidating embryos is increased and that it may be primarily associated with a better morphology and a better growth potential of developing embryos.

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Section: Discussionmentioning

confidence: 99%

Embryonic Production of Nitric Oxide and Its Role in Implantation: A Pilot Study

Battaglia

Ciotti

Notarangelo

et al. 2003

J Assist Reprod Genet

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“…A possible explanation is that, in vivo, arginine protects pancreatic b-cell from the diabetogenic effect of alloxan and promotes neogenesis of these cells (Méndez and De Haro, 2005;Vasilijevic et al, 2007), and thus, the ameliorative effects previously seen (Méndez and Palomar-Morales, 1999) are probably mediated by the recovering of b-cell function and insulin released in response to arginine administration (Grill and Herberg, 1993). Also, L-arginine could be transformed to nitric oxide (Novaro et al, 2002) or polyamines (Kwon et al, 2004), and these molecules may be responsible for the embryoprotective effects of in vivo administration of L-arginine.…”

Section: Discussionmentioning

confidence: 97%

Polyamines protect rat embryo in vitro from high glucose‐induced developmental delay and dysmorphogenesis

Chirino-Galindo

Baiza-Gutman

Barrera-Escorcia

et al. 2009

Birth Defects Research Pt B

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“…Previous works have demonstrated that NO is able to increase MMP2 and MMP9 activities in the uterus from both control and diabetic rats (Novaro et al 2002 and in term human placenta and trophoblast cells in culture (Pustovrh et al 2000, Novaro et al 2001. Several pathways have been proposed for the mechanisms of action of NO on MMPs expression and activity.…”

Section: Effect Of No On Mmps Activitiesmentioning

confidence: 97%

The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats

Pustovrh

Jawerbaum²,

White³

et al. 2007

Reproduction

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Matrix metalloproteinases (MMPs) play an important role in tissue remodeling that accompanies the rapid growth, differentiation, and structural changes of the placenta and several fetal organs. In the present study, we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH-diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP9 in the diabetic group. On the other hand, the NO donor did not modify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the fetoplacental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.

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Nitric oxide induces gelatinase A (matrix metalloproteinase 2) during rat embryo implantation

Cited by 38 publications

References 42 publications

Embryonic Production of Nitric Oxide and Its Role in Implantation: A Pilot Study

Embryonic Production of Nitric Oxide and Its Role in Implantation: A Pilot Study

Polyamines protect rat embryo in vitro from high glucose‐induced developmental delay and dysmorphogenesis

The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats

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