A 23-year-old woman, gravida 2 para 1, at 39 weeks gestation comes to the labor and delivery unit with regular painful contractions. The patient's first pregnancy was uncomplicated and resulted in a full-term, spontaneous vaginal delivery 3 years ago, and her current pregnancy has been uncomplicated. She takes a prenatal vitamin daily and has no chronic medical conditions. In response to rising estrogen levels, the patient's myometrial cells increase the expression of genes that encode the oxytocin receptor and connexin 43. These molecular changes most likely result in increased formation of which of the following?
Cell junctions | ||
Type | Proteins | Function |
Gap junction | Connexins | Intercellular |
Tight junction | Claudins, occludin | Paracellular barrier |
Adherens junction | Cadherins | Cellular anchor |
Desmosomes | Cadherins | |
Hemidesmosomes | Integrins | |
The initiation of labor requires a series of biochemical changes in the uterus and cervix mediated by endocrine changes (eg, increased estrogen & progesterone). Communicating gap junctions are especially important during labor and delivery, which require coordination and synchronization of individual myometrial (uterine smooth muscle) cells.
Gap junctions facilitate electrical and chemical communication between neighboring cells via a connexon, a connecting cylinder with a central channel composed of connexin proteins (eg, connexin 43). In preparation for labor, increasing estrogen levels stimulate upregulation of connexin 43, increasing formation of gap junctions between individual myometrial cells. An increase in gap junction density allows the passage of small ions between neighboring myometrial cells, resulting in coordinated, synchronous labor contractions.
Estrogen also increases the expression of uterotonic oxytocin receptors, Gq–coupled membrane receptors that increase intracellular calcium levels, heightening myometrial excitability.
(Choices A and B) Both adherens junctions and desmosomes are composed of cadherins, which are calcium-dependent adhesion proteins that bind epithelial cells together. The cytoplasmic anchor of adherens junctions is the actin filament, whereas the cytoplasmic anchor of desmosomes is the intermediate filament. Autoantibodies against desmoglein, a cadherin protein for desmosomes, are found in pemphigus vulgaris.
(Choice C) Fenestrae are transcellular pores within endothelial cells that facilitate increased solute exchange. They are found in capillaries perfusing the intestine, renal tubules, and endocrine glands.
(Choice E) Hemidesmosomes are similar to desmosomes but link cells to the basement membrane via integrins, transmembrane anchor proteins. Autoantibodies to hemidesmosomes cause bullous pemphigoid and pemphigoid gestationis.
(Choice F) Tight junctions (zonula occludens), composed of claudins and occludin, prevent paracellular passage of fluid and solutes. Tight junctions between capillary endothelial cells help form the blood-brain barrier.
Educational objective:
Gap junctions facilitate communication and coordination between cells and play an important role in labor contractions. Gap junctions are composed of connexin proteins, which are upregulated in the uterus in response to rising estrogen levels.