Chapter 42 Parturition © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.1 Changes in the cephalo- pelvic ratio through primate evolution. Relationship between the pelvic anatomy and the size of the fetal head at term in the human and chimpanzee, and an estimate of the cephalopelvic relationship of Australopithecus (2–4 million years ago) derived from the fossil record. Source: Adapted from Rosenberg and Trevathan.15 © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.2 Hormonal pathways regulating myometrial contractility. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.3 Changes in PG–endoperoxide synthase 2 (PTGS2) and hydroxyprostaglandin dehydrogenase (HPGD) activities in the gestational tissues (amnion, chorion, decidua, and myometrium) associated with the onset of human labor. Parturition is associated with increased PTGS2 activity in all tissues. HPGD is predominantly expressed by the chorion and effectively blocks amnion PGs from accessing the myometrium. Parturition is associated with decreased HPGD activity in the chorion that could allow more active PG to reach the myometrium. PGs are also produced by the myometrium at parturition and likely have autocrine and paracrine effects on contractility. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.4 Synthesis of biologically active PGs from membrane phospholipids, the key enzymes involved, the receptors with which they interact, and their effects on myometrial contractility. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.5 Comparison of tissue synthesis and changes in circulating progesterone (P4) and estradiol (E2) in human, ovine, and rodent pregnancy. In the human, the placenta produces progesterone throughout pregnancy, and there is no systemic decrease in P4 at parturition. In addition, the placenta produces estrogens (E2 (shown), estriol, estrone, and estetrol) from dehydroepiandrosterone (DHEA) supplied by the fetal adrenal cortex. In ovine pregnancy, the placenta is the principal source of P4. Late in gestation, activation of the fetal hypothalamic–pituitary– adrenal axis leads to a surge in cortisol that induces expression of P450c17 in the placenta, which converts P4 to androstenedione that can be used for estrogen synthesis. This causes a decrease in circulating P4 levels and a coordinated increase in circulating E2 levels. In rodent pregnancy, the maternal ovaries are the exclusive source of P4 (secreted by CLs) and E2 (secreted by developing follicles). At parturition, PGF2α produced by the decidua induces luteolysis, leading to systemic P4 withdrawal, and E2 levels increase in response to further ovarian follicle development, which is in response to increased gonadotropin exposure due to removal of P4 negative feedback to the maternal hypothalamus and pituitary. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42. 6 Organization of human PR-B and PR-A FIGURE 42.6 Organization of human PR-B and PR-A. The molecules can be divided into four functional domains: (1) the N domain at the N terminus, (2) the DNA-binding domain (DBD), (3) the hinge (H) domain, and (4) the ligand-binding domain (LBD). AF-1, AF-2, and AF-3 refer to transcription activation regions, and ID is the inhibitory domain that confers PR-A-mediated inhibition of PR-B. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.7 Positive-feedback hormonal loops in the physiology of parturition. Left: Endocrine feedback loop involving OT secreted from the hypothalamus–posterior pituitary in response to cervical distention induces contractions that further distend the cervix to increase pituitary OT release. Right: Paracrine feedback loop within the gestational tissues. Tissue-level inflammation induces functional progesterone withdrawal, which induces functional estrogen activation, which increases responsiveness to estrogens that augment PG synthesis and responsiveness to OT. PGs induce contractions and cervical ripening and augment tissue- level inflammation. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42.8 Schematic representation of maternal plasma CRH levels between 15 and 30 weeks of gestation in pregnancies destined to deliver preterm, at term, and postterm. A theoretical threshold for CRH-induced parturition is shown. The trajectory of CRH increase established early in gestation will influence when the threshold is reached. Source: From Ref. 476. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

FIGURE 42. 9 Schematic representation of the triggers for parturition FIGURE 42.9 Schematic representation of the triggers for parturition. Uterine quiescence and growth are promoted by the combined actions of progesterone and estrogens. Estrogens also promote pro-labor gene expression at the time of parturition, but this activity is inhibited by progesterone for most of pregnancy. Multiple physiological triggers for parturition function primarily by inhibiting the pro-gestational actions of progesterone. © 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition