Opposing actions of prostaglandins and oxytocin determine the onset of murine labor

Gross, Gil; Imamura, Toshihiro; Luedke, Christina; Vogt, Sherri K.; Olson, Lisa; Nelson, D. Michael; Sadovsky, Yoel; Muglia, Louis J.

doi:10.1073/pnas.95.20.11875

Cited by 221 publications

(204 citation statements)

References 25 publications

(23 reference statements)

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…Gene disruption of COX-1 or COX-2 in mice gives rise to distinct phenotypes (28)(29)(30). COX-1 null mice survive without evidence of gastric pathology and with decreased sensitivity to indocin induced gastric ulceration (28,29), as well as delayed parturition (31) and mild platelet abnormalities. In contrast, COX-2 null mice develop nephropathy and cardiac fibrosis (30).…”

mentioning

confidence: 99%

Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration

Rudnick

Perlmutter

Muglia

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

120

View full text Add to dashboard Cite

The liver responds to multiple types of injury with an extraordinarily well orchestrated and tightly regulated form of regeneration. The response to partial hepatectomy has been used as a model system to elucidate the molecular basis of this regenerative response. In this study, we used cyclooxygenase (COX)-selective antagonists and -null mice to determine the role of prostaglandin signaling in the response of liver to partial hepatectomy. The results show that liver regeneration is markedly impaired when both COX-1 and COX-2 are inhibited by indocin or by a combination of the COX-1 selective antagonist, SC-560, and the COX-2 selective antagonist, SC-236. Inhibition of COX-2 alone partially inhibits regeneration whereas inhibition of COX-1 alone tends to delay regeneration. Neither the rise in IL-6 nor the activation of signal transducer and activator of transcription-3 (STAT3) that is seen during liver regeneration is inhibited by indocin or the selective COX antagonists. In contrast, indocin treatment prevents the activation of CREB by phosphorylation that occurs during hepatic regeneration. These data indicate that prostaglandin signaling is required during liver regeneration, that COX-2 plays a particularly important role but COX-1 is also involved, and implicate the activation of CREB rather than STAT3 as the mediator of prostaglandin signaling during liver regeneration.

show abstract

mentioning

confidence: 99%

Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration

Rudnick

Perlmutter

Muglia

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

120

View full text Add to dashboard Cite

show abstract

“…At term gestation, and before the onset of labor, the expression of uterine COX-I augmented increasing the production of PGF 2␣ . Gross et al (16) reported that mice deficient in COX-I produced less PGF 2␣ at the end of pregnancy and presented a delay in the time of delivery, whereas the administration of PGF 2␣ restored it. Thus, COX-I was postulated as responsible for luteolytic PGF 2␣ synthesis and for the decrease in serum P (33).…”

Section: Discussionmentioning

confidence: 99%

“…Near term, cyclooxygenase I (COX-I) expression is augmented in the rat uterus (15). It is thought that luteolysis is caused by this early increase in COX-I followed by an increase in prostaglandin F 2␣ (PGF 2␣ ) secretion (16). When PGF 2␣ reaches the ovary, it triggers luteolysis and causes a fall in serum P (17).…”

mentioning

confidence: 99%

Epidermal growth factor prevents prepartum luteolysis in the rat

Ribeiro¹,

Aisemberg²,

Billi³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We have previously reported that intrauterine (i͞u) administration of epidermal growth factor (EGF 500 ng) on day (d) 21 of pregnancy delayed 19.0 ؎ 0.6 h the onset of labor. Progesterone (P) is secreted by ovarian corpora lutea (CL) throughout gestation in the rat. Prepartum CL regression due to increased uterine cyclooxygenase I and prostaglandin F 2␣ results in P withdrawal followed by labor. The aims of the present work were (i) to study whether EGF delayed-onset of labor was mediated by a mechanism that prevented CL regression; (ii) to determine amniotic fluid (AF) EGF in pregnant rats. Rats on d21 of pregnancy received i͞u EGF (500 ng) and were killed 0, 4, 8, 12, 24, and 48 h later. Control AF from rats on d13 and 18 -22 of pregnancy was obtained. EGF decreased uterine prostaglandin F 2␣ synthesis 8 h after treatment. Twelve hours after EGF injection, P reached its highest serum level and uterine cyclooxygenase I expression was undetectable. CL from rats killed 8 and 12 h after EGF were similar to those from rats on d13 of pregnancy, when serum P is maximum. EGF in AF increased throughout gestation, reached a maximum on d21, and decreased before the onset of labor. We suggest that the effect of EGF on the onset of labor was mediated by an early effect on the uterus that prevented prepartum CL regression.

show abstract

“…Murine genes that have been inactivated in the prostaglandin synthesis pathway have demonstrated that prostaglandins are essential for initiation of labor in the mouse (Sugimoto et al 1997, Uozumi et al 1997, Gross et al 1998. In humans, prostaglandins are used to augment labor, and prostaglandin synthesis inhibitors are used to delay delivery, implicating an important role for prostaglandins in human labor as well (Novy & Liggins 1980, Challis et al 1997, 2002, Weiss 2000, Goldenberg 2002.…”

Section: Introductionmentioning

confidence: 99%

Identification of transcription factors at the site of implantation in the later stages of murine pregnancy

Zhao¹,

Koon²,

Bethin³

2006

Reproduction

View full text Add to dashboard Cite

Despite medical advances, preterm delivery continues to complicate 12% of all births in the United States and is a major cause of neonatal deaths. One of the reasons that preterm labor continues to be a significant problem is that very little is understood about the factors involved in normal labor. Many investigators have studied parturition in the mouse and defined essential pathways for normal labor. Prostaglandins play an essential role in mouse labor and are important in human labor as well. We examined the 23 transcription factors from pregnant mouse uterus that change expression after the induction of cyclooxygenase-1, the enzyme that catalyzes the first committed step in prostaglandin synthesis. Using in situ hybridization, we have identified three of these transcription factors, Hoxa10, Hoxa11 and GILZ as being expressed in the decidua and regulated at the end of pregnancy. Both Hoxa10 and Hoxa11 are known to be critical for implantation, but very little is known about their roles in late gestation. GILZ has not previously been identified in the gravid uterus. In summary, we have identified three transcription factors that are regulated in the decidua at the end of pregnancy, suggesting a role in detachment of the fetus and placenta.

show abstract

Opposing actions of prostaglandins and oxytocin determine the onset of murine labor

Cited by 221 publications

References 25 publications

Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration

Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration

Epidermal growth factor prevents prepartum luteolysis in the rat

Identification of transcription factors at the site of implantation in the later stages of murine pregnancy

Contact Info

Product

Resources

About