Prostaglandin-induced cervical remodelling in humans in the first trimester is associated with increased expression of specific tight junction, but not gap junction proteins

Abstract

BackgroundProstaglandins (PG) are widely employed to induce cervical remodelling (CR) in pregnancy. However, the underlying molecular mechanisms are not fully elucidated. Tight junctions (TJ) and gap junctions (GJ) regulate paracellular and intercellular solute transport respectively but their role in the process of CR remains unexplored. We hypothesized that the synthetic prostaglandin E1 analogue Misoprostol (M), widely used in clinical practice to induce CR, may alter TJ and GJ expression as part of the changes in the extracellular matrix (ECM) associated with remodelling. We investigated the effects of Misoprostol exposure on the expression of cervical TJ (claudins 1, 2, 4, 5, 7 and occludin) and GJ (connexins 43, 30 and 26) in the 1st trimester.MethodsCervical biopsies were obtained from pregnant women and comparisons of TJ and GJ protein expression (by western blotting) and immunolocalisation (laser scanning confocal microscopy) made between those who were administered vaginal Misoprostol (n = 10) and those who were not (n = 5).ResultsWe found that Misoprostol-treated tissue (M+) had higher expression of Claudins 1,2,4,7 and occludin (p < 0.05) than untreated (M-) tissue. Expression levels of Claudins 1, 2 and 4 were positively correlated to interval from Misoprostol treatment to biopsy, whilst occludin was negatively correlated. Misoprostol-treated cervical tissue demonstrated more endothelial claudin-5 and occludin, whilst expression of GJs were unchanged.ConclusionOur observations suggest, for the first time, that increased expression of tight junction proteins may be one of the mechanisms by which Misoprostol induces CR in humans. Further studies are needed to explore if TJ proteins may be therapeutic targets to alter timing of CR in clinical practice.

Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

“…For JNK and p-JNK, it is known two bands will be detected: 46 and 54 kDa. All bands detected on blots were consistent with production information from the companies and other scientific reports which studied particular protein with antibodies ZO-1 (20,(51)(52)(53), E-Cadherin (20,39,52,53), Claudin-1 (20,53,54), 54), Occludin (52), Villin (45,55,56), JNK, p-JNK (40, 53, 57, 58), and ␤-actin (59). AvrA-e forward CAGGCCACAAAAGAAAAC AvrA-e reverse ATAACAGCCGCATCAAAC AvrA-r forward CCCAAGCTTATCTACCTCCCGGTGTCA AvrA-r reverse CGGGATCCTTGCGGGCGTCTATCTGT AvrA-cm forward…”

Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19

“…Previous studies have reported the expression of AJ and TJ proteins in chorionic villi of human placenta at term, finding that the STB expresses E-cadherin, ZO-1 and ZO-2, JAM-B, occludin, claudins -1, -3, -4, -5 -7 and -16, while the vessels in the parenchyma of chorionic villi display ZO-1, occludin, JAM-C, and claudins -1, -3, -4 and -5 [61][62][63]. ZO-1, JAM-C, and claudin-5 can be observed in large and small vessels, whereas occludin and claudins 1, -3 and -4 are mainly present in large placental vessels [61,62].…”

Androgens in pregnancy: roles in parturition

“…These cells secrete an extracellular matrix (ECM), which consists primarily of collagen, glycosaminoglycans and proteoglycans. Hormones including progestogens and E2, relaxin and prostaglandin can alter ECM composition and affect the mechanical strength of the cervix ( Ekman-Ordeberg et al , 2003 ; Simon and Einspanier, 2009 ; Ji et al , 2011 ; Ghule et al , 2012 ). The consequence of this process is remodelling of the cervix, which can be divided into four stages: softening (first trimester), ripening (second trimester), dilatation (third trimester) and reconstitution of the non-pregnant cervix post-partum ( Read et al , 2007 ).…”