PTGS2-Related PGE2 Affects Oocyte MAPK Phosphorylation and Meiosis Progression in Cattle: Late Effects on Early Embryonic Development

Nuttinck, Fabienne; Gall, Laurence; Ruffini, Sylvie; Laffont, Ludivine; Clément, Laetitia; Reinaud, Pierrette; Adenot, Pierre; Grimard, Bénédicte; Charpigny, Gilles; Guienne, B. Marquant-Le

doi:10.1095/biolreprod.110.088211

Cited by 45 publications

(51 citation statements)

References 45 publications

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“…Therefore, the increase in MI is due to a delay in nuclear maturation without compromising the developmental competence of the oocyte. This is in agreement with the previous data from Nuttinck et al (2011) who found that PTGS2 inhibition significantly increased oocytes at MI after 22 h and also showed that NS398 decreased embryo output rates on day 6 post fertilization but not on day 7. They also showed that total blastomere number was significantly lower in embryos obtained after PTGS2 inhibition, while no effect on total cell number in the blastocyst on day 7 could be seen in the present study.…”

Section: Discussionsupporting

confidence: 93%

“…Several studies have demonstrated that PTGS2-derived PGE 2 plays an important role in cumulus cell expansion and oocyte maturation in rodents (Eppig, 1981;Hizaki et al, 1999;Lim et al, 1997;Takahashi et al, 2006) but with fewer studies in cattle (Nuttinck et al, 2011), the role of PGE 2 in oocyte maturation is less characterized and it is not clear if PGE 2 can be used as an additive to improve oocyte competence. The present study examined the expression of genes involved in the synthesis of PGE 2 and PGF 2a in bovine COC and the role of exogenous PGE 2 supplementation during bovine oocyte maturation in the presence or absence of Gn.…”

Section: Introductionmentioning

confidence: 99%

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Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte maturation and cumulus cell expansion

Marei

Abayasekara

Wathes

et al. 2014

Reproductive BioMedicine Online

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(AA Fouladi-Nashta).Waleed Fawzy A Marei is a veterinarian and graduated from Cairo University, Egypt in 2001. He started his academic career in theriogenology in 2002 and obtained his MSc degree in 2005. He joined the reproduction research group at the Royal Veterinary College, London, UK and investigated the effects of fatty acids on oocyte quality and early embryo development for his PhD, awarded in 2010. He then pursued post-doctoral research in the same group, working on early embryo development and implantation. Currently, he is a lecturer on theriogenology at Cairo University. His interests are clinical applications of assisted reproduction technologies and feed additives to improve reproductive performance in farm animals.Abstract Prostaglandin E 2 (PGE 2 ) is an autocrine/paracrine factor which mediates gonadotrophin (Gn) stimulation of cumulus expansion and oocyte maturation in rodents. Its role in bovine oocyte maturation is less characterized. This study detected PTGS2 (COX2) and PGE synthases (PTGES1, PTGES2 and PTGES3) in bovine cumulus-oocyte complexes (COC). Only PTGS2 and PTGES1 expression changed during maturation. In Gn-free media, no cumulus expansion and $45% nuclear maturation was achieved, while Gn-induced maturation showed full cumulus expansion (score 3) and $87% maturation. PGE 2 supplementation without Gn induced mild cumulus expansion (score 0.5-1) but increased nuclear maturation to levels similar to those obtained with Gn alone. In the presence of Gn, exogenous PGE 2 did not affect expansion or nuclear maturation and subsequent embryo development. Treatment with PTGS2 selective inhibitor (NS398), PTGS2-specific siRNA or PTGER2-receptor antagonist (AH6809) resulted in $20-25% reduction in nuclear maturation. NS398 and AH6809 did not affect cumulus expansion. Most oocytes not reaching metaphase of second meiosis (MII) following NS398, AH6809 and PTGS2-specific siRNA treatments were at MI. After longer maturation, NS398-treated oocytes had normal MII rate and uncompromised embryo development. PGE 2 has a limited role in cumulus expansion in bovine COC but is important for the timing of Gn-induced nuclear maturation. RBMOnline

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte maturation and cumulus cell expansion

Marei

Abayasekara

Wathes

et al. 2014

Reproductive BioMedicine Online

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“…PTGER, the prostaglandin E (PGE) receptor, is expressed in oocytes and CCs. PGE-PTGER signaling regulates CCs expansion and reorganization, which is required for successful sperm attraction, capture, and penetration52. In our study, the expression of both PTGER2 and PTGER4 was higher in PCOS GV CCs and enhanced the proliferation of CCs.…”

Section: Discussionsupporting

confidence: 47%

Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients

Liu

Feng

et al. 2016

Sci Rep

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Polycystic ovary syndrome (PCOS) is a common frequent endocrine disorder among women of reproductive age. Although assisted reproductive techniques (ARTs) are used to address subfertility in PCOS women, their effectiveness is not clear. Our aim was to compare transcriptomic profiles of oocytes and cumulus cells (CCs) between women with and without PCOS, and assess the effectiveness of ARTs in treating PCOS patients. We collected oocytes and CCs from 16 patients with and without PCOS patients to categorize them into 6 groups according to oocyte nuclear maturation. Transcriptional gene expression of oocyte and CCs was determined via single-cell RNA sequencing. The ratio of fertilization and cleavage was higher in PCOS patients than in non-PCOS patients undergoing ARTs, and there was no difference in the number of high-quality embryos between the groups. Differentially expressed genes including PPP2R1A, PDGFRA, EGFR, GJA1, PTGS2, TNFAIP6, TGF-β1, CAV1, INHBB et al. were investigated as potential causes of PCOS oocytes and CCs disorder at early stages, but their expression returned to the normal level at the metaphase II (MII) stage via ARTs. In conclusion, ARTs can improve the quality of cumulus-oocyte complex (COC) and increase the ratio of fertilization and cleavage in PCOS women.

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“…Blocking prostaglandins (i.e. PTGS2) decreases cumulus expansion and slows the rate of embryo development in the in vitro bovine system (Nuttinck et al 2011). By contrast, higher PTGS2 mRNA levels occur in the cumulus cells of human oocytes expressing the highest developmental capacity (Gebhardt et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…PTGS2 is positively regulated by FSH, epidermal growth factor (EGF; Joyce et al 2001, Shimada et al 2006, and oocyte-secreted factors (Elvin et al 2000, Joyce et al 2001, Dragovic et al 2007. Because inhibiting PTGS2 during IVM can decrease cumulus expansion, oocyte maturation, and ultimately embryo production (Nuttinck et al 2011), we predicted that a seasonal difference in the production of resulting enzyme may indicate altered FSH function. EGF can promote oocyte maturation (Farin et al 2007, Hatoya et al 2009, Uhm et al 2010 and is necessary for FSH-induced meiotic resumption (Chen et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Hobbs

Howard²,

Wildt³

et al. 2012

Reproduction

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Domestic cat oocytes are seasonally sensitive to FSH. Compared with those collected during the breeding season, oocytes from the nonbreeding (NB) season require more FSH during in vitro maturation to achieve comparable developmental competence. This study tested the hypothesis that this seasonal variation was due to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor b (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte complexes (COCs) isolated from cat ovaries during the natural breeding vs NB seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth factor receptor (EGFR) were examined in mature COCs from both seasons that were a) recovered in vivo or b) matured in vitro with conventional (1 mg/ml) or high (10 mg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole ovaries during the NB compared with breeding season but were similar in immature COCs, whereas ESR2 levels did not differ in either group between intervals. We observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across maturation in COCs within but not between the two seasons. The lack of seasonal differentiation in FSH-related genes was not consistent with the decreased developmental capacity of oocytes fertilized during the NB season. These findings reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in vivo and in vitro. Furthermore, this decline is unrelated to changes in expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral follicles.

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PTGS2-Related PGE2 Affects Oocyte MAPK Phosphorylation and Meiosis Progression in Cattle: Late Effects on Early Embryonic Development

Cited by 45 publications

References 45 publications

Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte maturation and cumulus cell expansion

Role of PTGS2-generated PGE2 during gonadotrophin-induced bovine oocyte maturation and cumulus cell expansion

Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

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