title: Restoration of on-time embryo implantation corrects the timing of parturition in cytosolic phospholipase A2 group IVA deficient mice.
abstract: Cytosolic phospholipase A2 (cPLA2, PLA2G4A) catalyzes the release of arachidonic acid for prostaglandin synthesis by cyclooxygenase 1 (PTGS1) and cyclooxygenase 2 (PTGS2). Mice with Pla2g4a deficiency have parturition delay and other reproductive deficits, including deferred onset of implantation, crowding of implantation sites, and small litters. In this study, we examined the contribution of PLA2G4A to parturition in mice. Pla2g4a mRNA and protein expression were discretely localized in the term and preterm uterine luminal epithelium and colocalized with Ptgs1, but not Ptgs2, expression. The levels of PGE2, PGF2alpha, 6-keto-PGF1alpha, and TxB2 were significantly decreased in Pla2g4a-null uterine tissues, similar to Ptgs1-null uteri, consistent with predominance of PLA2G4A-PTGS1-mediated prostaglandin synthesis in preparation for murine parturition. Litter size was strongly associated with the timing of parturition in Pla2g4a-null mice but could not fully account for the parturition delay. Pla2g4a-null females that received PGE2 + carbaprostacyclin at the time of implantation delivered earlier (20.5 +/- 0.2 days vs. 21.6 +/- 0.2 days, P < 0.01), although litter size was not improved (4.6 vs. 4.4 pups per litter, P = 0.6). After correction for small litter size, multivariate analysis indicated that Pla2g4a-null mice given prostaglandin treatment to improve implantation timing had gestational length that was similar to wild-type and Pla2g4a heterozygous mice. These results indicate that, despite specific Pla2g4a expression and function in term gestation uteri, the delayed parturition phenotype in Pla2g4a-null mice is primarily due to deferral of implantation. The role of PLA2G4A in timely parturition appears to be critically related to its actions in early pregnancy.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Brown
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.forename: Bibhash C
authors.initials: BC
authors.lastname: Paria
authors.forename: Jeff
authors.initials: J
authors.lastname: Reese
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005260:Female; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008098:Litter Size / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D036801:Parturition / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D013997:Time Factors; D014599:Uterus / Q000378:metabolism*
chemical_list: D011453:Prostaglandins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D054513:Group IV Phospholipases A2; D015232:Dinoprostone
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