Preterm delivery is the leading cause of perinatal mortality and morbidity. Current tocolytics target myometrial contractions, a late step in labor cascade. Identifying earlier events parturition may lead to more effective therapeutic strategies. We hypothesized that inflammatory decidua (the maternal-fetal interface), characterized by leucocyte infiltration, are an early event during term preterm (PTL). Leucocyte abundance human pregnancies was quantified following PTL (idiopathic infection...

Abstract Progesterone suppresses uterine contractility acting through its receptors (PRA/B). The mechanism by which human labour is initiated in the presence of elevated circulating progesterone has remained an enigma since Csapo first theorized a functional withdrawal 1965. Here we report that vitro progesterone-liganded nuclear PRB forms complex including JUN/JUN homodimers and P54 nrb /Sin3A/HDAC to repress transcription key gene, Cx43 . In contrast, unliganded PRA paradoxically activates...

Abstract Recent evidence suggests that leukocytes infiltrate uterine tissues at or around the time of parturition, implicating inflammation as a key mechanism human labor. MCP-1 (also known C-C chemokine motif ligand 2, CCL-2) is proinflammatory cytokine up-regulated in myometrium during Myometrium was collected from pregnant rats across gestation and Total RNA proteins were subjected to real-time PCR ELISA, respectively. Ccl-2 gene protein expression significantly gravid rat before labor,...

Abstract This study aimed to determine the mechanism of uterine activation during labour, both term ( TL ) and preterm PTL ). We hypothesized that peripheral leucocytes are recruited tissues by locally produced cytokines where they contribute initiation parturition. Mouse uteri were collected i gestation, post‐partum PP ), ii initiated intrauterine infusion LPS (125 μg) or iii injection progesterone receptor antagonist RU 486 analysed for multiple cytokine expression levels real‐time...

Abstract Leucocyte infiltration in the decidua (maternal–foetal interface) before, during and after term ( TL ) preterm labour PTL was studied mouse. We also investigated mechanism of peripheral leucocyte recruitment into by analysing tissue cytokine profiles. Decidual tissues were collected late gestation, post‐partum PP ). initiated on gestational day 15 intrauterine injection Lipopolysaccharide LPS , 125 μg) or progesterone signalling antagonism RU 486. Animals killed . Decidua basalis...

In the present study, we determined contribution of myometrial hyperplasia, hypertrophy, and apoptosis to uterine growth during pregnancy. The changes in two endogenous markers cell replication, proliferating nuclear antigen (PCNA) protein expression bromodeoxyuridine (BrdU) incorporation, were studied. Myocyte hypertrophy was assessed by measuring protein:DNA ratio. levels antiapoptotic regulatory proteins (BCL2 BCL2L1) enzymes involved (caspases 3, 6, 7, 9, 10) immunoblotting throughout...

Evidence indicates that stretch of the uterus imposed by growing fetus contributes to onset labor. Previously we have shown mechanically stretching rat myometrial smooth muscle cells (SMCs) induces c- fos expression. To investigate this stretch-induced signaling, examined involvement mitogen-activated protein kinase (MAPK) family. We show SMCs a rapid and transient phosphorylation (activation) MAPKs: extracellular signal-regulated (ERK), c-Jun NH 2 -terminal (JNK), p38. The use selective...

Myometrial growth and remodeling during pregnancy depends on increased synthesis of interstitial matrix proteins. We hypothesize that the presence mechanical tension in a specific hormonal environment regulates expression extracellular (ECM) components uterus. tissue was collected from pregnant rats Gestational Days 0, 12, 15, 17, 19, 21, 22, 23 (labor), 1 day postpartum ECM analyzed by Northern blotting. Expression fibronectin, laminin β2, collagen IV mRNA low early gestation but...

Abstract Preterm birth ( PTB ) can lead to lifelong complications and challenges. Identifying monitoring molecular signals in easily accessible biological samples that diagnose or predict the risk of preterm labour PTL pregnant women will reduce prevent s. A number studies identified putative biomarkers for including protein, mi RNA hormones from various body fluids. However, these usually lack consistency reproducibility. Extracellular vesicles EV s) circulation have gained significant...

Decidual natural killer (dNK) cells are the predominant lymphocytes accumulated at maternal-fetal interface. Regulatory mechanism of dNK in preeclampsia, a gestational complication characterized by high blood pressure and increased proteinuria occurring after 20 weeks pregnancy, is not completely understood.Multi-parameter flow cytometry applied to investigate phenotype function freshly isolated from decidual samples or conditionally cultured TGFb stimulation.In we documented elevated...

Gap junctions are characteristically increased in the myometrium during term and preterm delivery thought to be essential for development of uterine contractions labour. Expression connexin43 (Cx43), major myometrial gap junction protein, is delivery. We have generated a mouse mutant (Cx43fl/fl:SM-CreERT2), which coding region Cx43 can specifically deleted smooth muscle cells at any given time point by application tamoxifen. By this approach, we were able study long-term effects on functions...

The adaptive growth of the uterus is a critical event that involves changes in cellular phenotypes throughout pregnancy. In early pregnancy, uterine due to hyperplasia smooth muscle cells (SMCs) within myometrium; however, major component myometrial occurs after mid-gestation. This study sought test hypothesis increase seen during late pregnancy SMC hypertrophy caused by mechanical stretch tissue growing fetus(es) providing direct measurements individual size. We employed stereological...

Abstract The progesterone receptor (PR) plays important roles in the establishment and maintenance of pregnancy. By dynamic interactions with coregulators, PR represses expression genes that increase contractile activity myometrium contribute to initiation labor. We have previously shown PTB-associated RNA splicing factor (PSF) can function as a corepressor. In this report, we demonstrated PSF heterodimer partner, p54nrb (non-POU-domain-containing, octamer binding protein), also...

Preterm birth (PTB) is the single most important cause of perinatal and infant mortality worldwide. Maternal infection can result in PTB. We investigated ability a Broad Spectrum Chemokine Inhibitor (BSCI) to prevent infection-induced PTB mice. was initiated pregnant mice by intraperitoneal injection lipopolysaccharide (LPS; 50 μg). Half received BSCI (10 mg/kg) 24 hrs prior immediately before LPS administration. The impact alone or plus assessed on (i) injection-to-delivery interval, foetal...

Abstract The onset of labour in rodents and humans is associated with physiological inflammation which manifested by infiltration activated maternal peripheral leukocytes (mPLs) into uterine tissues. Here, we used flow cytometry to immunophenotype mPLs throughout gestation labour, both term preterm. Peripheral blood was collected from non‐pregnant women pregnant the 1st, 2nd 3rd trimesters. Samples were also active at (TL) or preterm (PTL) compared not‐in‐labour (TNIL) (PTNIL). Different...

In most mammals, a withdrawal of the pro-gestational hormone progesterone (P4) is necessary for labor onset. murine cervix, P4 mediated by enzymes steroid 5-alpha-reductase type 1 (SRD5A1) and 20-alpha-hydroxysteroid-dehydrogenase (20α-HSD). Previously, we have shown that inflammatory stimuli induce 20α-HSD levels in uterine muscle (myometrium). Here, hypothesized (1) infectious inflammation alters both P4-metabolizing mouse which consequently ceases P4-mediated inhibition cervical...

The uterine smooth muscle (myometrium) is an immunomodulatory tissue capable of secreting multiple chemokines during pregnancy. We propose that before term labor, secreted as a result mechanical stretch the walls by growing fetus(es) induce infiltration maternal monocytes into myometrium, drive their differentiation macrophages, and pro-inflammatory (M1) polarization, leading to labor contractions. This study used high-throughput proteomic mass-spectrometry investigate underlying mechanisms...