Distinct phospholipase A2 enzymes regulate prostaglandin E2 and F2alpha production by bovine endometrial epithelial cells

Tithof, Patricia K.; Roberts, Mary P.; Guan, Wei; Elgayyar, Mona; Godkin, James D.

doi:10.1186/1477-7827-5-16

Cited by 52 publications

(61 citation statements)

References 45 publications

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“…This is in contrast to observed IFNT effects described in vitro (Asselin et al 1997a, 1997c, Parent et al 2002, Emond et al 2004, Tithof et al 2007, Godkin et al 2008. In addition, the release of all PG examined is strikingly concomitant, making it likely that the general rather than the specific synthases account for the vast increase in PG.…”

Section: Discussioncontrasting

confidence: 52%

“…Moreover, it has been discussed that the relative production of PGE 2 and PGF 2a may be more important than the absolute levels of individual-secreted PG, in the choice between embryo implantation and resumption of the estrous cycle (Asselin et al 1997a). IFNT has been made responsible for the reduced production of PGF 2a relative to PGE 2 evidenced by numerous in vitro studies (Asselin et al 1997a, 1997c, Parent et al 2002, Emond et al 2004, Tithof et al 2007, Godkin et al 2008. However, we find clear evidence that there is no difference in PGF 2a /PGE 2 ratio between cyclic and pregnant uteri in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

Reproduction

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Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF 1a (stable metabolite of PGI 2 ) was predominant followed by PGF 2a OPGE 2 OPGD 2 zTXB 2 (stable metabolite of TXA 2 ). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF 2a /PGE 2 ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF 1a (6.4 ng/ml) followed by PGF 2a (1.1 ng/ml) and PGE 2 (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI 2 and PGF 2a receptors were abundantly expressed by the trophoblast, abundant amounts of PGI 2 and PGF 2a in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE 2 in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

Reproduction

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“…Prostaglandins are produced from the common precursor AA, which is liberated from cell membranes by phospholipase A2 (PLA2) enzymes. The type of prostaglandin produced may depend on the PLA2 enzyme that is stimulated, where the PLA2 group 6 enzyme is associated with PGF accumulation, and PLA2 group 4C enzyme is associated with PGE accumulation (Tithof et al 2007). A predominant release of luteoprotective PGE following an E. coli infection of the uterus may mediate the prolonged luteal phases that are associated with bovine endometritis (Mateus et al 2003, Herath et al 2009.…”

Section: Discussionmentioning

confidence: 99%

Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions

MacKintosh¹,

Schuberth²,

Healy³

et al. 2013

Reproduction

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Epithelial cells of the endometrium secrete prostaglandins to regulate the bovine oestrous cycle and form a functional barrier to microbes. However, bacterial infection of the endometrium commonly causes infertility in dairy cattle by disrupting endometrial physiology. Epithelial cell cultures are used to study the mechanisms of physiology and pathology, but 2D cultures may not reflect the 3D complexity of the epithelium. In this study, a polarised epithelial cell transwell culture was developed, using transepithelial resistance (TER), to monitor epithelial integrity. Polarised epithelial cells were treated with oxytocin and arachidonic acid to test physiological function and with lipopolysaccharide (LPS) to mimic bacterial infection. Supernatants were analysed for prostaglandin E 2 (PGE), prostaglandin F 2a , the chemokine interleukin-8 (IL8) and the ability of supernatants to induce neutrophil migration. Confluent epithelial cells established polarity when TER was O1800 Ucm 2 and predominantly released prostaglandins basolaterally. In contrast, IL8 from epithelial cells accumulated apically and the supernatants were highly chemotactic for neutrophils. The striking exception was when the epithelial cells were treated with LPS in the apical or basolateral compartment independently, which led to the release of IL8 towards the treated compartment. Although stromal cells also accumulated PGE and IL8 in response to treatment, co-culture of stromal cells in the well below polarised epithelial cells did not influence cellular responses. In conclusion, polarised endometrial epithelial cells vectorially released prostaglandins and chemokines to reflect their respective mechanistic roles in physiology and pathology.

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“…Conversely, IFNT appeared to negatively influence the expression of PGFS, PLA2G6 and PGDH mRNA as there were fewer transcripts in the gravid compared with the nongravid (with less exposure to IFNT) horns. PGFS expression is reportedly downregulated in response to IFNT in bovine endometrium as is PLA2G6 activity, a phospholipase that catalyses the rate-limiting step in prostaglandin biosynthesis by hydrolysing arachidonic acid from membrane lipids (Tithof et al 2007). PGDH converts PGE 2 and PGF 2a to their inactive metabolites (PGEM and PGFM, respectively) and although Arosh et al (2004) described PGDH protein expression as unaffected by IFNT, they subsequently reported that mRNA and protein expression were not directly related during the oestrous cycle (Parent et al 2006).…”

Section: Evaluation Of the Bovine Uterine Environmentmentioning

confidence: 99%

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

Ledgard

Meier

Peterson

2011

Reprod. Fertil. Dev.

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Abstract. During previous investigations, the capacity of the cow to secrete prostaglandin in response to oxytocin has been linked with pregnancy outcome. The objective of the present study was to evaluate the predictive value of prostaglandin release to identify groups of cows as potentially superior (SR, low prostaglandin release) or inferior (IR, high prostaglandin release) for pregnancy outcome and to utilise these cows to investigate factors that contribute to optimum uterine conditions for early pregnancy. Animals were synchronised and received an in vitro-derived blastocyst on Day 7 post-oestrus. Tissues (trophoblast and endometrial) and uterine luminal fluid (ULF) were recovered 10 days later. Pregnancy rates were 94 and 78% for SR and IR cows, respectively. Of the pregnant SR cows, 69% had larged conceptuses (.24 cm) in contrast to 43% IR of cows. IR cows with small conceptuses (,12 cm) had significantly lower mean Day 3 and 5 post-oestrous progesterone concentrations than cows with large conceptuses. The expression of factors involved in the prostaglandin pathway, pregnancy and conceptus development were analysed via quantitative RT-PCR and Western blot analysis. Investigation of 16 endometrial gene transcripts indicated no differences between IR and SR cows except for osteopontin expression which, in uteri with large conceptuses, was 2-fold greater in SR than IR cows (P ¼ 0.02). There was greater expression of CTGF, OXTR, PGES, PGHS2 and UTMP mRNA in uteri of SR and IR cows that had large compared with small conceptuses (P , 0.05). More IFNT protein was recovered in SR compared with IR ULF (P , 0.03). SR cows with large conceptuses had less TIMP2 and legumain protein in their gravid, compared with their non-gravid horns (P # 0.02) whereas IR cows did not. The predictive value of prostaglandin release in response to oxytocin challenge does not appear to be an effective indicator of subsequent pregnancy rates in cows. Differences between the two groups appear to be associated with subtle differences in progesterone and uterine protein concentrations that may be related to differences in conceptus size.

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Distinct phospholipase A2 enzymes regulate prostaglandin E2 and F2alpha production by bovine endometrial epithelial cells

Cited by 52 publications

References 45 publications

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

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