title: Mechanisms leading to increased risk of preterm birth in growth-restricted guinea pig pregnancies.
abstract: Intrauterine growth restriction (IUGR) is a risk factor for preterm labor; however, the mechanisms of the relationship remain unknown. Prostaglandin (PG), key stimulants of labor, availability is regulated by the synthetic enzymes, prostaglandin endoperoxidases 1 and 2 (PTGS1 and 2), and the metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (HPGD). We hypothesized that IUGR increases susceptibility to preterm labor due to the changing balance of synthetic and metabolizing enzymes and hence greater PG availability. We have tested this hypothesis using a surgically induced IUGR model in guinea pigs, which results in significantly shorter gestation. Myometrium, amnion, chorion, and placentas were collected from sham operated or IUGR pregnancies, and PTGS1 and HPGD protein expression were quantified throughout late gestation (>62 days) and labor. The PTGS1 expression was significantly upregulated in the myometrium of IUGR animals, and chorionic HPGD expression was markedly decreased (P < .01 and P < .001, respectively). These findings suggest a shift in the balance of PG production over metabolism in IUGR pregnancies leads to a greater susceptibility to preterm birth.
authors.affiliation: 1School of Biomedical Sciences and Pharmacy, University of Newcastle, New South Wales, Australia.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Palliser
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Kelleher
authors.forename: Toni N
authors.initials: TN
authors.lastname: Welsh
authors.forename: Tamas
authors.initials: T
authors.lastname: Zakar
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hirst
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000378:metabolism*; D006168:Guinea Pigs; D011247:Pregnancy; D047928:Premature Birth / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*
keywords: 15-hydroxyprostaglandin dehydrogenase; growth restriction; myometrium; preterm labor; prostaglandins