The exact causes of labor onset remain inconclusive and cannot be fully explained by a singular mechanism. It is currently believed that labor onset results from the combined action of multiple factors.
Inflammatory Response Hypothesis
Numerous studies indicate that inflammation plays a pivotal role in initiating labor. The maternal-fetal interface creates an immunological microenvironment composed of immune-active cells in the decidua and the cytokines they secrete. The maternal immune regulation system contributes to maintaining this microenvironment, enabling a state of immunological tolerance toward the fetus during pregnancy. Changes in the immune system occur during labor onset, manifesting both systemically and at the maternal-fetal interface. These changes in immune balance may play a significant role in triggering labor. Additionally, an influx and chemotaxis of neutrophils and macrophages are observed in the uterine decidua and cervix prior to labor, accompanied by an increase in the expression of inflammatory factors. These findings suggest the presence of a noninfectious inflammatory process.
Endocrine Regulation Theory
During labor onset, uterine smooth muscle transitions from a quiescent state to an active state. This transition is regulated by various endocrine hormones, ultimately leading to uterine contractions and cervical dilation, initiating labor.
Prostaglandins (PGs)
Prostaglandins are paracrine and autocrine hormones primarily acting locally in the area of their secretion. Increased prostaglandin synthesis in the uterus is a key factor in initiating labor. The main known actions of prostaglandins include:
- Inducing strong and coordinated uterine contractions.
- Promoting cervical ripening.
- Upregulating oxytocin receptor expression, enhancing the uterus's sensitivity to oxytocin.
Steroid Hormones
Human estrogen during pregnancy is synthesized by the placental-fetal unit. Increased estrogen levels contribute to labor initiation through the following mechanisms:
- Inducing functional changes in the uterus.
- Stimulating prostaglandin production, as the myometrium, endometrium, and cervical mucosa all produce prostaglandins capable of promoting uterine contractions and cervical ripening.
- Promoting actin accumulation in the uterine fundus to facilitate contractions.
- Increasing the membrane potential activity of uterine myocytes, enhancing uterine sensitivity to oxytocin and promoting cervical ripening.
In contrast, progesterone promotes nitric oxide (NO) synthesis, inhibits the formation of intercellular connections, and downregulates the synthesis of prostaglandins, calcium channels, and oxytocin receptor expression. While an increased estrogen-to-progesterone ratio may not be the primary driver for labor in humans, both hormones play crucial roles in maintaining pregnancy and initiating labor.
Oxytocin
Research suggests that oxytocin plays a significant, although nonessential, role in labor onset. During pregnancy, maternal circulating oxytocin levels remain stable but gradually increase with the progression of labor, peaking just before the fetus is delivered in the second stage. In contrast, uterine oxytocin receptor expression increases throughout pregnancy, thereby enhancing uterine sensitivity to oxytocin. Oxytocin indirectly promotes labor onset by stimulating the release of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in the fetal membranes. It also directly induces uterine contractions via mechanisms mediated by oxytocin receptors or calcium channels.
Mechanical Stimulation
This mechanism is also referred to as the uterine tension theory. As pregnancy progresses, the increasing uterine volume and the stretching tension of the uterine wall heighten its sensitivity to contractions. Toward the end of pregnancy, the amniotic fluid volume gradually decreases while fetal growth continues, resulting in close contact between the fetus and the uterine wall, particularly in the lower uterine segment and cervical region. Additionally, the Frankenhauser nerve plexus located in the cervical region may be stimulated by the descent of the presenting fetal part, inducing uterine contractions.
Functional Changes in the Uterus
Under the influence of endocrine hormones, the uterus undergoes functional changes characterized by the formation of intercellular gap junctions between myocytes and an increase in intracellular calcium ion levels. Specifically, when oxytocin binds to oxytocin receptors on uterine myocytes, ion channels on the cell membrane are activated, leading to a rise in intracellular free calcium ions and triggering uterine contractions. Furthermore, oxytocinase secreted by the placenta degrades oxytocin, and the balance between these factors is associated with the initiation of labor.