Klotz Communications: Evolution of hormones during pregnancy
Endocrinology of human parturitionLes hormones de l’accouchement

https://doi.org/10.1016/j.ando.2016.04.025Get rights and content

Abstract

The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The “final common pathway” to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.

Résumé

Les mécanismes impliqués dans la grossesse et l’accouchement sont très complexes et concernent la mère, le fœtus et le placenta. La voie finale commune jusqu’à la délivrance est composée par des voies interactives, de nature inflammatoire et endocrinienne qui font pencher la balance en faveur de la contractilité de l’utérus et la dilatation du col. Ces mécanismes impliquent les rôles de nombreux acteurs hormonaux : progestérone, estrogènes, CRH, ocytocine et prostaglandines. Les modifications complémentaires dans le col de l’utérus, causées par les prostaglandines, la relaxine et la diminution de l’action de la progestérone, conduisent à l’effacement et la dilatation du col utérin. Les voies neuronales, hormonales, inflammatoires et immunitaires, initient le début du travail. L’unité utéro-placentaire joue un rôle majeur pour la synthèse et la libération de médiateurs de l’accouchement.

Introduction

Parturition is a coordinated process of transition from a quiescent myometrium to an active rhythmically contractile state requiring complex interplay between placental, fetal and maternal compartments. The precise mechanisms involved in initiation of labor are thought to involve functional progesterone withdrawal, increased estrogen bioavailability, corticotrophin releasing hormone (CRH) and neuroendocrine mediators and finally, increased responsiveness of the myometrium to prostaglandins and oxytocin [1]. Labor at term may be regarded best physiologically as a release from the inhibitory effects of pregnancy on the myometrium rather than as an active process mediated by uterine stimulants [2]. It involves an integrated set of changes within the maternal tissues of the uterus (myometrium, decidua, and uterine cervix), which occur gradually over a period of days to weeks. Such changes include an increase in prostaglandin synthesis and release within the uterus, an increase in the myometrial gap junction formation, and up-regulation of myometrial oxytocin receptors. Indeed, endocrine or paracrine-autocrine factors from the feto-placental unit bring about a switch in the pattern of myometrial activity [3]. In fact, human parturition is an inflammatory and endocrine event, where the two systems interact modulating labor onset and progression [4].

In the past, the placenta was believed to be a largely passive organ mainly responsible for delivering nutrients to the fetus. With progress in obstetric research, this concept has gradually shifted to one that recognizes the placenta as a transient endocrine organ and a central regulator of maternal–placental–fetal physiology. Thus, the placenta ensures appropriate physiologic milieus for normal growth and development of fetal, placental, and maternal tissues necessary for a successful pregnancy. Indeed, the placenta represents a very metabolically active organ during parturition. It is a source of a large number of “information” molecules that, when released, can exert their biologic effects on the placenta itself but can also enter the maternal and fetal circulation, thus acting as autocrine, paracrine, and endocrine factors [5], [6].

Placenta produces a large variety of molecules including steroid hormones, hypothalamic-pituitary hormones, neuropeptides, growth factors and cytokines, involved in parturition [7]. Steroid hormones include the common female gonadal steroid hormones, progesterone and estrogens. It is noteworthy that the placenta produces also hormones that are known to be produced by neuroendocrine organs, such as oxytocin, gonadotrophin-releasing hormone (GnRH), opioids and CRH.

However, the fetus itself plays a role in initiation of labor, through the secretion of neurohormones and other stimulators of prostaglandin synthesis [8].

Thus, inflammation, mechanical distension of the uterus at term and hormonal paracrine and autocrine signalling between the feto-placental unit and the mother seem to promote the initiation of human parturition through coordinated activation of stimulatory pathways and loss of uterine quiescence, which enables contractions to occur.

Section snippets

Phases of human parturition

Pregnancy may be considered as consisting of four parturitional phases (Fig. 1). During the first parturitional phase (phase 0 – quiescent phase) the uterus is kept in a quiescent state through the action of progesterone and other minor factors such as prostacyclin (PGI2), relaxin, parathyroid hormone-related peptide (PTHrP), calcitonin gene-related peptide, vasoactive intestinal peptide and nitric oxide (NO). All these agents act mediate an increased intracellular concentrations of cyclic

Estrogens

Estrogens are essential for uterine development and function, playing a key role in uterine contractility. Human pregnancy is characterized by a typical hyperestrogenic state. The placenta is the primary source of estrogens, and concentrations of estrogens increase in the maternal circulation with increasing gestational age [1]. Placental estrone and 17β-estradiol are derived primarily from maternal C19 androgens (testosterone and androstenedione), whereas estriol is derived almost exclusively

Conclusion

The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. Despite extensive research, the integrated mechanisms underlying the onset of human parturition are not yet fully elucidated [73]. Inflammation is central in the process of labor, while prostaglandins, CRH, Ucns and oxytocin are key placental factors which mediate both endocrine (metabolism, immune function, cardiovascular changes) and paracrine (uterine

Disclosure of interest

The authors declare that they have no competing interest.

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