Cyclooxygenase 2 (COX2) expression and prostaglandin synthesis in neonatal rat testicular germ cells: Effects of acetaminophen and ibuprofen

Manku, Gurpreet; Papadopoulos, Philippos; Boisvert, Annie; Culty, Martine

doi:10.1111/andr.12727

Cited by 17 publications

(22 citation statements)

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“…Interestingly, we recently reported that neonatal gonocytes express COX2 and other enzymes of the prostaglandin pathway, and produce prostaglandins (PG) E2 and PGF2a [19]. Moreover, blocking PGE2 and PGF2a synthesis with ibuprofen for 24 h correlated with a partial decrease in RA-induced differentiation in PND3 gonocytes [19].…”

Section: Discussionmentioning

confidence: 99%

“…Cell viability was assessed using a Trypan blue exclusion assay, by counting live and trypan blue-positive gonocytes as previously described [19], and viability was expressed as the mean ± SEM of the percentage of live cells against the total number of gonocytes in 3 independent experiments, each performed with triplicates.…”

Section: Cell Viabilitymentioning

confidence: 99%

“…Total RNA was extracted from cell pellets using the PicoPure RNA isolaton kit (Arcturus, Mountain View, CA, USA) and digested with DNase I (Qiagen, Santa Clarita, CA, USA), followed by cDNA synthesis with a single-strand cDNA transcriptor synthesis kit (Roche Diagnostics, Indianapolis, IN, USA), as previously described [18,19]. Quantitative real-time PCR (qPCR) was performed using SYBRgreen PCR Master Mix kit (Bio-Rad, Hercules, CA, USA) on a LightCycler 480 (LC480, Roche Diagnostics) [18].…”

Section: Rna Extraction and Real-time Quantitative Pcr (Q-pcr) Analysismentioning

confidence: 99%

“…For IHC, PND3 testis samples were fixed with 4% paraformaldehyde solution (PFA), paraffin embedded, and 4 to 6 µm thick sections were made. IHC and ICC analyses were performed as previously described [18,19,23,25]. Briefly, the slides were dewaxed, rehydrated, treated for antigen retrieval, and then with a blocking reagent in PBS.…”

Section: Immunohistochemistry (Ihc)/immunocytochemistry (Icc)mentioning

confidence: 99%

“…Extensive cell remodeling takes place during the proliferation, relocation and differentiation of neonatal gonocytes, in part regulated by the ubiquitin proteasome system [18]. We recently reported that neonatal gonocytes express high levels of cyclooxygenase 2 (COX2) and produce prostaglandins [19]. While COX2 and prostaglandins were reported to regulate ROS production in Sertoli cells [20], in other cell types such as the kidney mesanglial cell, ROS were shown to regulate COX2 expression and prostaglandin synthesis [21].…”

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confidence: 99%

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Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

et al. 2019

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Peroxiredoxins (PRDXs) are antioxidant enzymes that protect cells from oxidative stress and play a role in reactive oxygen species (ROS)-mediated signaling. We reported that PRDXs are critical for human fertility by maintaining sperm viability and regulating ROS levels during capacitation. Moreover, studies on Prdx6 −/− mice revealed the essential role of PRDX6 in the viability, motility, and fertility competence of spermatozoa. Although PRDXs are abundant in the testis and spermatozoa, their potential role at different phases of spermatogenesis and in perinatal germ cells is unknown. Here, we examined the expression and role of PRDXs in isolated rat neonatal gonocytes, the precursors of spermatogonia, including spermatogonial stem cells. Gene array, qPCR analyses showed that PRDX1, 2, 3, 5, and 6 transcripts are among the most abundant antioxidant genes in postnatal day (PND) 3 gonocytes, while immunofluorescence confirmed the expression of PRDX1, 2, and 6 proteins. The role of PRDXs in gonocyte viability was examined using PRDX inhibitors, revealing that the 2-Cys PRDXs and PRDX6 peroxidases activities are critical for gonocytes viability in basal condition, likely preventing an excessive accumulation of endogenous ROS in the cells. In contrast to its crucial role in spermatozoa, PRDX6 independent phospholipase A 2 (iPLA 2 ) activity was not critical in gonocytes in basal conditions. However, under conditions of H 2 O 2 -induced oxidative stress, all these enzymatic activities were critical to maintain gonocyte viability. The inhibition of PRDXs promoted a two-fold increase in lipid peroxidation and prevented gonocyte differentiation. These results suggest that ROS are produced in neonatal gonocytes, where they are maintained by PRDXs at levels that are non-toxic and permissive for cell differentiation. These findings show that PRDXs play a major role in the antioxidant machinery of gonocytes, to maintain cell viability and allow for differentiation.PRDXs are classified depending on the cysteine residues (Cys) in their active site, that will react with peroxides. They comprise the 2-Cys PRDX1 to 4, the atypical 2-Cys PRDX5, and the 1-Cys PRDX6, which has the particularity of being bifunctional, with both peroxidase and calcium-independent phospholipase A 2 (iPLA 2 ) activities [4]. The 2-Cys PRDX1 to 4 are homodimers in which the thiol of a cysteine residue of one PRDX subunit gets oxidized, then further reacts with the thiol group of the catalytic cysteine of the other subunit, forming a disulfide bond between the two subunits. By contrast, in the atypical PRDX5, 2 Cys of the same chain react upon oxidation to form an intrasubunit disulfide bond. Inactive PRDXs are then reactivated by a reduction of the disulfide bonds by thioredoxin (TRX), itself further reactivated by TRX reductase (TRD), using NADPH as a reducing equivalent. In the case of PRDX6, since the enzyme has only one catalytic Cys, the oxidized thiol will be reduced by the glutathione-GSH-transferase P1 (GSTP1) system [4][5][6].Studies in PRDXs kno...

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Section: Discussionmentioning

confidence: 99%

Section: Cell Viabilitymentioning

confidence: 99%

Section: Rna Extraction and Real-time Quantitative Pcr (Q-pcr) Analysismentioning

confidence: 99%

Section: Immunohistochemistry (Ihc)/immunocytochemistry (Icc)mentioning

confidence: 99%

mentioning

confidence: 99%

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Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

et al. 2019

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Hypoxia, NSAIDs, and autism: A biocultural analysis of stressors in gametogenesis

Burke

2024

American J Hum Biol

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Cultural and generational trends have increasingly favored “anti‐inflammatory” action, innovating a new class of analgesic, non‐steroidal anti‐inflammatory drugs (NSAIDs) in the 20th century. The modern human body has been molded over evolutionary time and while acknowledging inflammation can be pathologically entwined, it also serves an important role in healthy folliculogenesis and ovulation, shaping cues that drive needed vascular change. This review argues that because of anti‐inflammatory action, the cultural invention of NSAIDs represents a particular stressor on female reproductive‐age bodies, interacting with natural, underlying variation and placing limits on healthy growth and development in the follicles, creating potential autism risk through hypoxia and mutagenic or epigenetic effects. Since testes are analogs to ovaries, the biological grounding extends naturally to spermatogenesis. This review suggests the introduction of over‐the‐counter NSAIDs in the 1980s failed to recognize the unique functioning of reproductive‐age bodies, challenging the cyclical inflammation needed for healthy gamete development. NSAIDs are framed as one (notable) stressor in an anti‐inflammatory era focused on taming the risks of inflammation in modern human life.

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Long-term exposure to environmentally relevant concentrations of ibuprofen and aluminum alters oxidative stress status on Danio rerio

Sánchez-Aceves

Pérez-Álvarez

Gómez-Oliván

et al. 2021

Comparative Biochemistry and Physiology Part C: Toxicology &

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Cyclooxygenase 2 (COX2) expression and prostaglandin synthesis in neonatal rat testicular germ cells: Effects of acetaminophen and ibuprofen

Cited by 17 publications

References 74 publications

Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

Hypoxia, NSAIDs, and autism: A biocultural analysis of stressors in gametogenesis

Long-term exposure to environmentally relevant concentrations of ibuprofen and aluminum alters oxidative stress status on Danio rerio

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