Oviduct prostacyclin functions as a paracrine factor to augment the development of embryos

Huang, Joanne; Goldsby, Jennifer S.; Arbab, Farinaz; Melhem, Ziad; Aleksic, Nena; Wu, Kenneth K.

doi:10.1093/humrep/deh520

Cited by 27 publications

(25 citation statements)

References 14 publications

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“…These findings indicate that other factors must be involved in the upregulation during the estrous cycle, e.g., FSH or LH. Immunohistochemical studies in human (Huang et al 2002) and in mouse (Huang et al 2004) revealed that COX-1 was localized in the epithelial lining as well as in the smooth muscle cells, which is similar to our findings in the bovine oviduct.…”

Section: Discussionsupporting

confidence: 89%

Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Odau¹,

Gabler²,

Holder³

et al. 2006

Journal of Endocrinology

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The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi-or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A 2 (sPLA 2 IB, cPLA 2 a, and cPLA 2 b) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA 2 b showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA 2 IB and cPLA 2 a mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA 2 IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17b-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA 2 a, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.

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Section: Discussionsupporting

confidence: 89%

Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Odau¹,

Gabler²,

Holder³

et al. 2006

Journal of Endocrinology

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“…The levels of PGE 2 and PGI 2 increase in the fallopian tubes (oviduct) following pregnancy, and these 2 prostaglandins, also produced in embryos, enhance embryo cell numbers, hatching, and implantation [77][78][79][80][81][82][83]. PGE 2 was found to have a positive affect on the growth of hematopoietic stem cell progenitors obtained from zebrafish and mouse embryonic stem cells [84].…”

Section: Discussionmentioning

confidence: 96%

Proliferation and Pluripotency of Human Embryonic Stem Cells Maintained on Type I Collagen

Jones

Chu

Pendleton

et al. 2010

Stem Cells and Development

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Human embryonic stem cells (hESC) require a balance of growth factors and signaling molecules to proliferate and retain pluripotency. Conditioned medium (CM) from a human embryonic germ-cell-derived cell culture, SDEC, was observed to support the growth of hESC on type I collagen (COL I) and on Matrigel (MAT) biomatricies. After 1 month, the population doubling of hESC grown in SDEC CM on COL I was equivalent to that of hESC grown in mouse embryonic fibroblast (MEF) CM on MAT. hESC grown in SDEC CM on COL I expressed OCT4, NANOG, SSEA-4, alkaline phosphatase (AP), and TRA-1-60; retained a normal karyotype; and were capable of forming teratomas. DNA microarray analysis was used to compare the transcriptional profiles of SDEC and the less supportive WI38 and Detroit 551 human cell lines. The mRNA level of secreted frizzledrelated protein (sFRP-1), a known antagonist of the WNT=b-catenin signaling pathway, was significantly reduced in SDEC as compared with the other 2 cell lines, whereas the mRNA levels of prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) and prostaglandin I 2 synthase (PGIS), two prostaglandin biosynthesis genes, were significantly increased in SDEC. The level of sFRP-1 protein was significantly reduced, and levels of 2 prostaglandins that are downstream products of PTGS2 and PGIS, prostaglandin E 2 and 6-keto-prostaglandin F 1a , were significantly elevated in SDEC CM compared with WI38, Detroit 551, and MEF CM. Further, addition of purified sFRP-1 to SDEC CM reduced the proliferation of hESC grown on COL I as well as MAT in a dosedependent manner.

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“…COX-2 gene deficiency causes multiple defects in female reproduction (12); COX-2-derived PGI 2 is critical for embryo development from oviduct dilation to facilitation of embryo transfer (43), to embryo hatching (44) and implantation and decidualization through a non-PGI 2 receptor pathway (45,46). Reproductive capability in female COX-1 Ͼ COX-2 mice was partially, but not completely, rescued by targeted COX-1 exchange, which further confirms that the two isoforms are not completely functionally interchangeable.…”

Section: Discussionmentioning

confidence: 99%

Targeted Cyclooxygenase Gene (Ptgs) Exchange Reveals Discriminant Isoform Functionality

Fan

Hui

et al. 2007

Journal of Biological Chemistry

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The prostaglandin G/H synthase enzymes, commonly termed COX-1 and COX-2, differ markedly in their responses to regulatory stimuli and their tissue expression patterns. COX-1 is the dominant source of "housekeeping" prostaglandins, whereas COX-2 synthesizes prostaglandins of relevance to pain, inflammation, and mitogenesis. Despite these distinctions, the two enzymes are remarkably conserved, and their subcellular distributions overlap considerably. To address the functional interchangeability of the two isozymes, mice in which COX-1 is expressed under COX-2 regulatory elements were created by a gene targeting "knock-in" strategy. In macrophages from these mice, COX-1 was shown to be lipopolysaccharide-inducible in a manner analogous to COX-2 in wild-type macrophages. However, COX-1 failed to substitute effectively for COX-2 in lipopolysaccharide-induced prostaglandin E 2 synthesis at low concentrations of substrate and in the metabolism of the endocannabinoid 2-arachidonylglycerol. The marked depression of the major urinary metabolite of prostacyclin in COX-2 null mice was only partially rescued by COX-1 knock-in, whereas the main urinary metabolite of prostaglandin E 2 was rescued totally. Replacement with COX-1 partially rescued the impact of COX-2 deletion on reproductive function. The renal pathology consequent to COX-2 deletion was delayed but not prevented, whereas the corresponding peritonitis was unaltered. Insertion of COX-1 under the regulatory sequences that drive COX-2 expression indicated that COX-1 can substitute for some COX-2 actions and rescue only some of the consequences of gene disruption. Manipulation of COX-2 also revealed a preference for coupling with distinct downstream prostaglandin synthases in vivo. These mice will provide a valuable reagent with which to elucidate the distinct roles of the COX enzymes in mammalian biology.

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Oviduct prostacyclin functions as a paracrine factor to augment the development of embryos

Abstract: Mouse oviducts synthesized maximal PGI2 during day 2-3 p.c., coinciding with the transformation of 2-cell embryos to morulae. The results suggest that oviduct-derived PGI2 may enhance embryo development in a paracrine fashion.

Cited by 27 publications

References 14 publications

Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Proliferation and Pluripotency of Human Embryonic Stem Cells Maintained on Type I Collagen

Targeted Cyclooxygenase Gene (Ptgs) Exchange Reveals Discriminant Isoform Functionality

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