Overview of current research in parturition

The mechanism of human parturition is not understood and further research i nto 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, nota bly the sheep, parturition is preceded by an activation of the fetal hypoth alamic-pituitary-adrenal axis. However, in primates this axis has a support ive, 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 apparen t fall. in maternal progesterone levels. Gene targeting experiments in mice have demonstrated the critical role of prostaglandin FP receptors, necessa ry to mediate the luteolytic effect of PGF(2 alpha) before parturition, mos taglandin synthesis is required for the onset and progress of labour as dem onstrated by experiments with cPLA(2)- and PGHS-1-deficient mice. The impor tance of local tissue conversion of progesterone to reduced androgens in th e regulation of cervical ripening has been demonstrated in 5 alpha -reducta se-deficient mice. The chronic and ubiquitous gene inactivation obtained wi th conventional methods has disadvantages, in that it may allow the activat ion of compensating pathways, making the interpretation of results difficul t. This problem may be overcome by using pulsed and tissue-selective gene k nockout strategies. The study of human parturition is complicated by the ta ck of access to direct experimentation, whereas the endocrine differences b etween species make it difficult to extrapolate animal data to humans. Howe ver, the development of genomic/proteomic technologies that allow the simul taneous screening of thousands of genes and gene products in small samples of tissue, and new methods to study the biochemistry of receptors and prote ins involved in smooth muscle physiology promise new insights into the cont rol of human labour. Nevertheless, the integration of rapidly expanding kno wledge into a complete understanding of the roles of the mother and the fet us in the initiation of parturition, and the development of selective medic ation for the effective management of preterm labour remain an arduous chal lenge for the nest decade.