Secretion of placental peptide hormones: functions and trafficking

Abstract

The placenta is a dynamic endocrine organ that plays a crucial role in fetal development by secreting a diverse array of peptide hormones that regulate maternal and fetal physiology. These hormones, including human chorionic gonadotropin (hCG), human placental lactogen (hPL), and placental growth hormone (hPGH), among others, are essential for pregnancy maintenance, fetal growth, and metabolic adaptation. Dysregulation of the secretory machinery and the levels of these hormones in circulation is associated with a myriad of pregnancy-related disorders. Despite their significance, the mechanisms governing their intracellular trafficking and secretion remain incompletely understood. This review synthesizes current knowledge on the secretion pathways of placental hormones, highlighting the interplay between constitutive and regulated secretion, and the challenges in defining these mechanisms due to the unique structure of the syncytiotrophoblast. We also discuss how emerging technologies, such as 2D and 3D placental models and advanced protein trafficking assays, can provide deeper insights into the regulation of placental hormone secretion. Understanding these processes will not only enhance our knowledge of placental biology but also provide new avenues for diagnosing and treating pregnancy-related disorders.

Keywords: cell biology; human placenta; peptide hormones; pregnancy; secretion.

Figure 1

Graphic representation of early stages of human placenta development. (A) Preimplantation embryo, showing the external trophectoderm cell layer that protects the inner cell mass or embryo proper, in close contact with a layer of uterine epithelial cells that rest on top of the decidua. (B, C) Early post-implantation embryo, showing the primitive syncytium surrounded by lacunae and primary villi made out of cytotrophoblasts. (D) First trimester fully developed placenta. Inset shows the detailed cellular architecture of an anchoring villus. The cytotrophoblast cell column keeps this villus attached to the decidua and provides the interstitial extravillous trophoblasts that invade nearby spiral arteries, plugging them first and remodeling them later in pregnancy.

Figure 2

Temporal patterns of major placental peptide hormone secretion across pregnancy. Graphical representation of the maternal serum concentrations (expressed as a percentage of maximum value) of key placental hormones during gestation. Human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) peak during the first trimester and decline thereafter (104, 250). Placental growth hormone (hPGH), human placental lactogen (hPL), leptin, insulin-like growth factor-I (IGF-I), and vascular endothelial growth factor/soluble fms-like tyrosine kinase-1 (VEGF/sFLT-1) progressively increase during the second and third trimesters (–256). Proopiomelanocortin (PMOC) shows a steady rise throughout pregnancy that plateus during the second trimester (257). Finally, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and activin/inhibin demonstrate a marked elevation toward late gestation (–261).

Figure 3

Schematic representation of the main secretion pathways in a cell. Active endocytosis and recycling through sorting endosomes allows the cell the control of cargo internalization and the reutilization of certain receptors depending on the intracellular demands. Cargo and receptors no longer required by the cell are degraded inside late endosomes and lysosomes, that receive lysosomal-specific degradative enzymes via direct trafficking from the Golgi or indirectly from the plasma membrane. Constitutive secretion brings Golgi newly synthesized in secretory vesicles (SeV) or recycled cargo directly back to the plasma membrane. In contrast, regulated secretion involves the packaging of cargo into highly-regulated secretory granules (SGs). Sorting of specific cargo from immature secretory granules constitutes constitutive-like secretion pathways.