PARTURITION 1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659907/ a) Kota, S. K., Gayatri, K., Jammula, S., Kota, S. K., Krishna, S. V., Meher, L. K., & Modi, K. D. (2013). Endocrinology of parturition. Indian journal of endocrinology and metabolism, 17(1), 50–59. https://doi.org/10.4103/2230-8210.107841 b) primary c) “A variety of endocrine systems play a role in the maintenance of uterine quiescence and the onset of parturition, with its attendant increase in uterine contractility and cervical ripening. There are many factors that can tip the balance in favor of delivery early, late, or on time. These factors, such as prostaglandins or inflammatory cytokines, may directly affect the contractile mechanisms. Other factors, such as oxytocin, CRH, or relaxin, may indirectly alter the actions of complementary systems.” 2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563697/ a) Reinl, E. L., & England, S. K. (2015). Fetal-to-maternal signaling to initiate parturition. The Journal of clinical investigation, 125(7), 2569–2571. https://doi.org/10.1172/JCI82576 b) primary c) “Within the myometrial smooth muscle cells, cytokines activate the proinflammatory transcription factor NF-κB, which induces expression of several genes that promote parturition. These include receptors for the contraction inducers (uterotonins) oxytocin (5) and prostaglandin F2α (PGF2α) (6) and the prostaglandin synthase enzyme cyclooxygenase-2” 3) https://pubmed.ncbi.nlm.nih.gov/29376493/ a) Salomon, C., Nuzhat, Z., Dixon, C. L., & Menon, R. (2018). Placental Exosomes During Gestation: Liquid Biopsies Carrying Signals for the Regulation of Human Parturition. Current pharmaceutical design, 24(9), 974–982. https://doi.org/10.2174/1381612824666180125164429 b) secondary c) “Recent studies suggest that placental exosomes are involved in maternal-fetal inmmunotolerance, maternal systemic inflammation and nutrient transport.” AND “Extracellular vesicles, namely exosomes, may be an integral component of these signaling events by transporting specific signals to prepare the maternal physiology to initiate parturition.” 4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001499/ a) Menon, R., Bonney, E. A., Condon, J., Mesiano, S., & Taylor, R. N. (2016). Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition. Human reproduction update, 22(5), 535–560. https://doi.org/10.1093/humupd/dmw022 b) secondary c) “The clocks and alarms set and activated by circulating pregnancy hormones, senescing fetal membranes, decidua and myometrium propagate signals that initiate the process of parturition. The final process is ultimately affected by cervical effacement and dilatation, allowing a progressive and controlled delivery of the fetus.” AND “At least one fetal paracrine clock, utilizing surfactant lipoproteins, regulates gestation by signaling via the fetal membranes and maternal myometrium when its lungs have developed the capacity for the transition from the aqueous environment of the amniotic cavity to aerobic environment outside.” 5) https://www.sciencedirect.com/science/article/pii/S0303720710004193?via%3Dihub a) Golightly, E., Jabbour, H. N., & Norman, J. E. (2011). Endocrine immune interactions in human parturition. Molecular and cellular endocrinology, 335(1), 52–59. https://doi.org/10.1016/j.mce.2010.08.005 b) primary c) “The fact that the progesterone receptor antagonist mifepristone is an effective agent for induction of labour to soften the cervix and increase uterine sensitivity to uterotonic agents (Hapangama and Neilson, 2009) does suggest that a role exists for some form of progesterone withdrawal being involved in the initiation of human parturition.” AND “It is clear that an intricate web of interactions exists between components of the endocrine and immune systems in order to regulate this process, and that disorders within it may lead to significant complications for both mother and infant.” 6) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632866/ a) Norwitz, E. R., Bonney, E. A., Snegovskikh, V. V., Williams, M. A., Phillippe, M., Park, J. S., & Abrahams, V. M. (2015). Molecular Regulation of Parturition: The Role of the Decidual Clock. Cold Spring Harbor perspectives in medicine, 5(11), a023143. https://doi.org/10.1101/cshperspect.a023143 b) secondary c) “Advancing gestational age is associated with a withdrawal of active suppression and/or an enhanced sensitivity of the decidua to signals capable of inducing inflammation. This promotes the release of a variety of biologically active inflammatory mediators (primarily PGs) leading to the onset of labor.” 7) https://pubmed.ncbi.nlm.nih.gov/25905197/ a) Tal, R., Taylor, H. S., Burney, R. O., Mooney, S. B., & Giudice, L. C. (2015). Endocrinology of Pregnancy. In K. R. Feingold (Eds.) et. al., Endotext. MDText.com, Inc. b) primary c) “The precise mechanisms involved in human parturition are thought to involve CRH, functional progesterone withdrawal, increased estrogen bioavailability, and finally, increased responsiveness of the myometrium to prostaglandins and oxytocin.” AND “Human parturition exemplifies the interplay between placental, fetal, and maternal compartments, characterized by increased estrogen bioavailability, functional progesterone withdrawal, increased CRH synthesis and release, culminating in increased responsiveness of the myometrium to prostaglandins and oxytocin” 8) https://link.springer.com/article/10.14310/horm.2002.1371 a) Iliodromiti, Z., Antonakopoulos, N., Sifakis, S. et al. Endocrine, paracrine, and autocrine placental mediators in labor. Hormones 11, 397–409 (2012). https://doi.org/10.14310/horm.2002.1371 b) primary c) “Once fetal maturity is reached, the fetal hypothalamus and placenta secrete CRH, which releases adrenocorticotropic hormone (ACTH) from fetal pituitary and fetal adrenals which produce cortisol and DHEA-S, the latter being aromatized to estrogens by the placenta.” AND “The main pathway starts from placental CRH, exploits fetal DHEA-S to produce estrogen environment and, through prostaglandins, results in myometrial contractions and cervical ripening, thus inducing labor. A variety of mediators interact in complex ways producing positive feedback loops of the main pathway.” 9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063701/ a) Makieva, S., Saunders, P. T., & Norman, J. E. (2014). Androgens in pregnancy: roles in parturition. Human reproduction update, 20(4), 542–559. https://doi.org/10.1093/humupd/dmu008 b) primary c) “Androgens are believed to be critical for cervical remodeling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens in myometrial relaxation via non-genomic, ARindependent pathways critical for the pregnancy reaching term” 10) https://pubmed.ncbi.nlm.nih.gov/25248577/ a) Voltolini, C., & Petraglia, F. (2014). Neuroendocrinology of pregnancy and parturition. Handbook of clinical neurology, 124, 17–36. https://doi.org/10.1016/B978-0-444-59602-4.00002-2 b) primary c) “CRH, Ucns, and oxytocin are key placental neuroendocrine factors which mediate both endocrine (metabolism, immune function, cardiovascular changes) and paracrine (uterine contractility, local hormone production) mechanisms involved in term and preterm birth” 11) https://academic.oup.com/edrv/article/31/6/783/2354753 a) Felice Petraglia, Alberto Imperatore, John R. G. Challis, Neuroendocrine Mechanisms in Pregnancy and Parturition, Endocrine Reviews, Volume 31, Issue 6, 1 December 2010, Pages 783–816, https://doi.org/10.1210/er.2009-0019 b) secondary c) “The CRH/Ucn peptides, produced in the placenta, are now implicated as important neuroendocrine mediators in the physiology of pregnancy and parturition. CRH is recognized as a hypothalamic neurohormone regulating ACTH release from the anterior pituitary lobe, which in turn stimulates cortisol secretion from the adrenal cortex.” 12) https://academic.oup.com/jcem/article/85/12/4421/2851677 a) Gerson Weiss, Endocrinology of Parturition, The Journal of Clinical Endocrinology & Metabolism, Volume 85, Issue 12, 1 December 2000, Pages 4421– 4425, https://doi.org/10.1210/jcem.85.12.7074 b) secondary c) “These mechanisms involve a shift from progesterone to estrogen dominance, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandin activity. Decreased nitric oxide (NO) activity and increased influx of calcium into myocytes are both required for uterine contractibility.” 13) https://www.sciencedirect.com/science/article/pii/S0003426616300427?via%3Dihub a) Vannuccini, S., Bocchi, C., Severi, F. M., Challis, J. R., & Petraglia, F. (2016). Endocrinology of human parturition. Annales d'endocrinologie, 77(2), 105–113. https://doi.org/10.1016/j.ando.2016.04.025 b) secondary c) “The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta.” AND “In the third phase of parturition (phase 2 – stimulation phase), the uterus can be stimulated by uterotonics including prostaglandins, oxytocin and CRH. The biochemical events within the uterus resemble an inflammatory reaction, with increased synthesis of cytokines.” 14) https://elifesciences.org/articles/58343 a) Rokas, A., Mesiano, S., Tamam, O., LaBella, A., Zhang, G., Muglia, L., 2020. Developing a theoretical evolutionary framework to solve the mystery of parturition initiation. eLife 9, e58343. https://doi.org/10.7554/eLife.58343 b) secondary c) “Parturition may be initiated by multiple pathways, some of which are part of the normal timing process and provide complementary, partially overlapping mechanisms, while others (e.g. pathways associated with response to infection) may override pregnancy maintenance signals to provide failsafe mechanisms that serve the survival interests of the mother (and her future reproductive potential) and the fetus/neonate” AND “Cortisol plays a key role in promoting fetal organ maturation in humans, however, parturition in women is not initiated by fetal HPA activity.”
