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Abstract Background Nerves and neurotrophic growth factors are emerging promoters of cancer growth. The precursor for Nerve Growth Factor (proNGF) is overexpressed in thyroid cancer, but its potential role as a clinical biomarker has not been reported. Here we have examined the value of proNGF as a serum and biopsy-rinse biomarker for thyroid cancer diagnosis. Methods Patients presenting for thyroid surgery or biopsy were enrolled in separate cohorts examining serum (n = 204, including 46 cases of thyroid cancer) and biopsy-rinse specimens (n = 188, including 26 cases of thyroid cancer). ProNGF levels in clinical samples were analysed by ELISA. Univariate and multivariate statistical analyses were used to compare proNGF levels with malignancy status and clinicopathological parameters. Results ProNGF was not detected in the majority of serum samples (176/204, 86%) and the detection of proNGF was not associated with thyroid cancer diagnosis. In the few cases where proNGF was detected in the serum, thyroidectomy did not affect proNGF concentration, demonstrating that the thyroid was not the source of serum proNGF. Intriguingly, an association between hyperthyroidism and serum proNGF was observed (OR 3.3, 95% CI 1.6–8.7 p = 0.02). In biopsy-rinse, proNGF was detected in 73/188 (39%) cases, with no association between proNGF and thyroid cancer. However, a significant positive association between follicular lesions and biopsy-rinse proNGF was found (OR 3.3, 95% CI 1.2–8.7, p = 0.02). Conclusions ProNGF levels in serum and biopsy-rinse are not increased in thyroid cancer and therefore proNGF is not a clinical biomarker for this condition.

The characteristics of fetal membrane cells and their phenotypic adaptations to support pregnancy or promote parturition are defined by global patterns of gene expression controlled by chromatin structure. Heritable epigenetic chromatin modifications that include DNA methylation and covalent histone modifications establish chromatin regions permissive or exclusive of regulatory interactions defining the cell-specific scope and potential of gene activity. Non-coding RNAs acting at the transcriptional and post-transcriptional levels complement the system by robustly stabilizing gene expression patterns and contributing to ordered phenotype transitions. Here we review currently available information about epigenetic gene regulation in the amnion and the chorion laeve. In addition, we provide an overview of epigenetic phenomena in the decidua, which is the maternal tissue fused to the chorion membrane forming the anatomical and functional unit called choriodecidua. The relationship of gene expression with DNA (CpG) methylation, histone acetylation and methylation, micro RNAs, long non-coding RNAs and chromatin accessibility is discussed in the context of normal pregnancy, parturition and pregnancy complications. Data generated using clinical samples and cell culture models strongly suggests that epigenetic events are associated with the phenotypic transitions of fetal membrane cells during the establishment, maintenance and termination of pregnancy potentially driving and consolidating the changes as pregnancy progresses. Disease conditions and environmental factors may produce epigenetic footprints that indicate exposures and mediate adverse pregnancy outcomes. Although knowledge is expanding rapidly, fetal membrane epigenetics is still in an early stage of development necessitating further research to realize its remarkable basic and translational potential.

We present a hypothesis for a mechanism involving self-organization of small functional units that leads to organ-level synchronization of uterine contractions in human labor. This view is in contrast to the long-held presumption that the synchronized behavior of the uterus is subject to well-defined internal organization (as is found in the heart) that exists prior to the onset of labor. The contractile units of the uterus are myocytes, which contract in response to both mechanical stretch and electrical stimulation. Throughout pregnancy progesterone maintains quiescence by suppression of “contraction-associated proteins” (CAPs). At the end of pregnancy a functional withdrawal of progesterone and an increasingly estrogenic environment leads to an increase in the production of CAPs. One CAP of particular importance is connexin 43, which creates gap junctions between the myocytes that cause them to become electrically coupled. The electrical connectivity between myocytes, combined with an increase in intrauterine pressure at the end of pregnancy shifts the uterus towards an increasingly unstable critical point, characterized by irregular, uncoordinated contractions. We propose that synchronous, coordinated contractions emerge from this critical point through a process of self-organization, and that the search for a uterine pacemaker has been unfruitful for the sole reason that it is non-existent.