Prokineticin 1 induces a pro-inflammatory response in murine fetal membranes but does not induce preterm delivery

Abstract

The mechanisms that regulate the induction of term or preterm delivery (PTD) are not fully understood. Infection is known to play a role in the induction of pro-inflammatory cascades in uteroplacental tissues associated with preterm pathological parturition. Similar but not identical cascades are evident in term labour. In the current study, we used a mouse model to evaluate the role of prokineticins in term and preterm parturition. Prokineticins are multi-functioning secreted proteins that signal through G-protein-coupled receptors to induce gene expression, including genes important in inflammatory responses. Expression of prokineticins (Prok1 and Prok2) was quantified in murine uteroplacental tissues by QPCR in the days preceding labour (days 16–19). Prok1 mRNA expression increased significantly on D18 in fetal membranes (compared with D16) but not in uterus or placenta. Intrauterine injection of PROK1 on D17 induced fetal membrane mRNA expression of the pro-inflammatory mediators Il6, Il1b, Tnf, Cxcl2 and Cxcl5, which are not normally up-regulated until D19 of pregnancy. However, intrauterine injection of PROK1 did not result in PTD. As expected, injection of lipopolysaccharide (LPS) induced PTD, but this was not associated with changes in expression of Prok1 or its receptor (Prokr1) in fetal membranes. These results suggest that although Prok1 exhibits dynamic mRNA regulation in fetal membranes preceding labour and induces a pro-inflammatory response when injected into the uterus on D17, it is insufficient to induce PTD. Additionally, prokineticin up-regulation appears not to be part of the LPS-induced inflammatory response in mouse fetal membranes.

Endocrine Gland-Derived Endothelial Growth Factor (EG-VEGF) Is a Potential Novel Regulator of Human Parturition1

“…However, repeated injections of EG-VEGF to gravid mice during late gestation did not trigger any contractions, and mice proceeded normally to term [13]. These findings confirm the notion that EG-VEGF is rather a protecting than a constrictor factor during late pregnancy.…”

“…Figure1 shows that circulating EG-VEGF levels significantly increased toward the end of pregnancy, suggesting a potential role of this factor in the late processes of parturition. The source of EG-VEGF could not be of placental origin because both our group and Lannagan et al [7,13] showed that placental EG-VEGF production does not increase toward the Comparison of EG-VEGF serum levels in nonlaboring pregnant women during the second and third trimester of pregnancy. A total of 25 serum samples were analyzed (second-trimester samples, n ¼ 14; thirdtrimester samples, n ¼ 11).…”

“…Former publications that identified EG-VEGF and its analog, prokineticin 2, reported roles in the regulation of contractility for these factors in the gastrointestinal smooth muscle [2], suggesting a potential role for EG-VEGF in the mechanism of parturition, a multistep process that includes myometrial contraction, cervical ripening, and fetal membrane (FM) rupture [12]. In relation to the FM, Lannagan et al [13] recently showed that EG-VEGF mRNA expression increased significantly in murine FM on Day 18 (as compared with Day 16) but not in the uterus or placenta. Nevertheless, intrauterine injection of EG-VEGF in gravid mice did not result in preterm delivery, suggesting a different role for EG-VEGF in the mechanism of parturition [13].…”

“…In relation to the FM, Lannagan et al [13] recently showed that EG-VEGF mRNA expression increased significantly in murine FM on Day 18 (as compared with Day 16) but not in the uterus or placenta. Nevertheless, intrauterine injection of EG-VEGF in gravid mice did not result in preterm delivery, suggesting a different role for EG-VEGF in the mechanism of parturition [13]. To date, no studies have examined the expression of EG-VEGF and its receptors, PROKR1 and PROKR2, in the human FM during late human pregnancy and in relation to the labor process.…”

Leptin, Interleukin-6, soluble receptors for VEGF and oxidized LDL in pregnancies complicated preeclampsia, premature delivery risk, obesity

“…Ожирение как состояние низкоуровневого воспаления является фактором риска развития ПЭ. Однако не всякое воспаление индуцирует преждевременные роды [2] и не каждое ожирение переходит в ПЭ. Другими словами, существуют определенные условия, позволяющие реализовать ту или иную патологию.…”