Overview of Current Research in Parturition

Abstract

The mechanism of human parturition is not understood and further research into this important physiological process is needed. Preterm labour remains a major cause of perinatal mortality and morbidity and there is controversy about the effectiveness of current tocolytic agents. In some species, notably the sheep, parturition is preceded by an activation of the fetal hypothalamic‐pituitary‐adrenal axis. However, in primates this axis has a supportive, rather than essential, role. A fall in maternal progesterone levels is a prerequisite for parturition in most mammals and this takes place either through increased conversion of progesterone to oestrogens in the placenta, or through the demise of the corpus luteum of pregnancy, depending on the species. In primates and guinea‐pigs parturition occurs without an apparent fall in maternal progesterone levels. Gene targeting experiments in mice have demonstrated the critical role of prostaglandin FP receptors, necessary to mediate the luteolytic effect of PGF2α before parturition. Prostaglandin synthesis is required for the onset and progress of labour as demonstrated by experiments with cPLA2‐ and PGHS‐1‐deficient mice. The importance of local tissue conversion of progesterone to reduced androgens in the regulation of cervical ripening has been demonstrated in 5α‐reductase‐deficient mice. The chronic and ubiquitous gene inactivation obtained with conventional methods has disadvantages, in that it may allow the activation of compensating pathways, making the interpretation of results difficult. This problem may be overcome by using pulsed and tissue‐selective gene knockout strategies. The study of human parturition is complicated by the lack of access to direct experimentation, whereas the endocrine differences between species make it difficult to extrapolate animal data to humans. However, the development of genomic/proteomic technologies that allow the simultaneous screening of thousands of genes and gene products in small samples of tissue, and new methods to study the biochemistry of receptors and proteins involved in smooth muscle physiology promise new insights into the control of human labour. Nevertheless, the integration of rapidly expanding knowledge into a complete understanding of the roles of the mother and the fetus in the initiation of parturition, and the development of selective medication for the effective management of preterm labour remain an arduous challenge for the next decade.

Role of CD38 in myometrial Ca2+transients: modulation by progesterone

“…The mechanism by which the myometrium is prepared for labor is not completely understood. However, it appears that cytokines such as TNF-␣ are involved in this mechanism (2,3,18,21,23,24). We (1) have previously shown that incubation of myometrial cells with TNF-␣ for Ͼ12 h increases expression of CD38, elevates intracellular levels of cADPR, and augments oxytocin-induced Ca 2ϩ transients.…”

“…The mechanisms regulating the preparation of the myometrium for labor are not completely understood. It appears that placental steroids and proinflammatory cytokines play an important role in the preparation of the myometrium for contraction and labor (2,3,18,21,23,24). Thus it is important to understand the signaling pathways regulated by hormones and cytokines in myometrial cells.…”

Effects of combined progesterone and 17β-estradiol treatment on the transcriptome of cultured human myometrial smooth muscle cells

“…Its withdrawal at any stage of pregnancy initiates muscle contraction leading to labor (52). G protein-coupled receptor (GPCR) activation and reversible Ca 2ϩ -dependent phosphorylation of myosin light chain (MLC), catalyzed by myosin light chain kinase (MLCK), is a major determinant of smooth muscle contraction (7,34). The regulation of contractility is described by GO terms such as G protein-coupled signaling, cell communication, channel activity (voltage-gated cation channels), all of which were very significant in the analysis of the significantly modulated genes in P4/E2 and RU486-treated cells in this study.…”

Ringwomb in ewes and does

“…έναρξη της διαδικασίας του τοκετού εξαρτάται κατά κύ ριο λόγο από τον άξονα υποθάλαμος-υπόφυση-επινεφρί-δια του εμβρύου (Bernal 2001). Σημαντικό ρόλο στη δια δικασία του τοκετού διαδραματίζει το μυομήτριο, λόγω της ικανότητας του να συσπάται υπό την επίδραση νευρι κών, χημικών και μηχανικών παραγόντων (Carbillon και συν.…”