Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism

Wolfson, Manuel Luis; Schander, Julieta Aylén; Bariani, María Victoria; Correa, Fernando; Franchi, A.M.

doi:10.1016/j.ejphar.2015.11.005

Cited by 16 publications

(15 citation statements)

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“…Using a transwell system, we found that in the co‐cultures of PBMC from LPS‐treated mice with deciduas from untreated mice, there was a reduction in decidual FAAH activity and that this effect was reversed when PBMC were obtained from LPS‐treated mice co‐treated with progesterone. Similarly, we had previously shown that in vitro cultured PBMC from in vivo LPS‐treated pregnant mice showed and increased NO production and that in vivo co‐administration with progesterone reversed this effect (Wolfson et al, ). These results are in agreement with previous observations showing that progesterone and other progestins exert immunomulatory effects during pregnancy (Raghupathy et al, ; Aisemberg et al, ; Wolfson et al, ; Tan et al, ).…”

Section: Discussionsupporting

confidence: 55%

“…Indeed, in vivo administration of LPS to 7‐day pregnant mice is accompanied with an increased leukocyte infiltration of the decidua (Ogando et al, ; Wolfson et al, ) which is not present in the in vitro experiments. Moreover, in our in vivo approach, the PBMC from LPS‐treated mice showed increased NO production (Wolfson et al, ) and the leukocyte‐infiltrated decidua from these mice expressed higher mRNA levels of cytokines and chemokines (Wolfson et al, ). Overall, the results presented here might resemble more faithfully a pathophysiological process than our previous in vitro approach.…”

Section: Discussionmentioning

confidence: 93%

“…However, excessive production of NO has been associated with peroxidative damage (Franco and Estévez, ), embryotoxicity (Barroso et al, ), and early pregnancy loss (Haddad et al, ; Athanassakis et al, ; Ogando et al, ). Previous reports from our lab showed that LPS enhanced the production of NO (Wolfson et al, ) and altered components of the endocannabinoid system (eCS) in pregnant mice (Wolfson et al, , ).…”

mentioning

confidence: 90%

“…However, during maternal infection with gram‐negative bacteria, the presence of LPS might contribute to the activation and recruitment of peripheral blood mononuclear cells (PBMC) into reproductive tissues (Ogando et al, ). Moreover, LPS induced an increased nitric oxide (NO) release by PBMC from both pregnant and non‐pregnant mice (Wolfson et al, ). NO is a short‐lived molecule that acts as a mediator of multiple cellular functions.…”

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confidence: 99%

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Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS‐Induced Embryo Resorption Model

Wolfson

Aisemberg

Correa

et al. 2016

Journal Cellular Physiology

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Maternal infections with gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue plays an important role in the establishment of a local inflammatory process that results in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss. Here, we sought to investigate whether the infiltrating PBMC modulates the decidual endocannabinoid tone and the molecular mechanisms involved. PBMC isolated from 7-day pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-day pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measured by radioconvertion, total decidual protein nitration by Western blot (WB), and decidual FAAH nitration by immunoprecipitation followed by WB. We found that co-culture of PBMC obtained from LPS-treated mice increased the level of nitration of decidual FAAH, which resulted in a negative modulation of decidual FAAH activity. Interestingly, co-treatment with progesterone or aminoguanidine prevented this effect. We found that LPS-treated PBMC release high amounts of nitric oxide (NO) which causes tyrosine nitration of decidual FAAH, diminishing its enzymatic activity. Inactivation of FAAH, the main degrading enzyme of anandamide and similar endocannabinoids, could lead to an increased decidual endocannabinoid tone with embryotoxic effects. J. Cell. Physiol. 232: 1441-1447, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS‐Induced Embryo Resorption Model

Wolfson

Aisemberg

Correa

et al. 2016

Journal Cellular Physiology

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“…In terms of immunity, it can regulate the balance of cytokines and influence the activity of natural killer cells [5,6]. It suppresses uterine contraction, by enhancing nitric oxide production in the lining of the uterus [7,8]. Furthermore, progesterone may reduce the spiral arteries' pulsatility index and resistance index; thus, it can increase uteroplacental circulation [9].…”

Section: Introductionmentioning

confidence: 99%

Baseline Levels of Serum Progesterone and the First Trimester Pregnancy Outcome in Women with Threatened Abortion: A Retrospective Cohort Study

Deng

Chen

et al. 2020

BioMed Research International

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Objective. The relationship between serum progesterone and the first trimester pregnancy outcome of threatened abortion is still controversial. Therefore, we aimed to further study the association between these two parameters. Methods. The present study is an observational retrospective cohort study. A total of 726 participants who had threatened abortion from a hospital in Guangdong, China, were included in this study from 17th August 2011 to 30th October 2018. The exposure variable and the outcome variable were serum progesterone measured at baseline and early pregnancy outcome, respectively. Covariates involved in this study included patients' basic demographics, obstetric history, and clinical information. Results. A negative association and a saturation effect were detected between serum progesterone and the first trimester pregnancy outcome. When progesterone <90.62 nmol/L, an increase in 1 nmol/L of serum progesterone was associated with 3% decrease of the risk of miscarriage (OR: 0.97, 95% CI: 0.95-0.98). Conclusion. There was a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L. Our findings can better assist the clinician in understanding patients' conditions and making medical decisions.

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Progesterone Response Element Variation in the OXTR Promoter Region and Paternal Care in New World Monkeys

et al. 2016

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Paternal care is a complex social behavior common in primate species with socially monogamous mating systems and twin births. Evolutionary causes and consequences of such behavior are not well understood, nor are their neuroendocrine and genetic bases. However, the neuropeptide oxytocin (OXT) and its receptor (OXTR) are associated with parental care in mammalian lineages. Here we investigated the interspecific variation in the number of progesterone response elements (PREs) in the OXTR promoter region of 32 primate species, correlating genetic data with behavior, social systems, and ecological/life-history parameters, while controlling for phylogeny. We verified that PREs are only present in New World monkeys and that PRE number is significantly correlated with the presence of paternal care in this branch. We suggest that PRE number could be an essential part of the genetic repertoire that allowed the emergence of taxon-specific complex social behaviors, such as paternal care in marmosets and tamarins.

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Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism

Cited by 16 publications

References 50 publications

Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS‐Induced Embryo Resorption Model

Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS‐Induced Embryo Resorption Model

Baseline Levels of Serum Progesterone and the First Trimester Pregnancy Outcome in Women with Threatened Abortion: A Retrospective Cohort Study

Progesterone Response Element Variation in the OXTR Promoter Region and Paternal Care in New World Monkeys

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