Motile Cilia in Female and Male Reproductive Tracts and Fertility

Abstract

Motile cilia are evolutionarily conserved organelles. In humans, multiciliated cells (MCCs), assembling several hundred motile cilia on their apical surface, are components of the monolayer epithelia lining lower and upper airways, brain ventricles, and parts of the reproductive tracts, the fallopian tube and uterus in females, and efferent ductules in males. The coordinated beating of cilia generates a force that enables a shift of the tubular fluid, particles, or cells along the surface of the ciliated epithelia. Uncoordinated or altered cilia motion or cilia immotility may result in subfertility or even infertility. Here, we summarize the current knowledge regarding the localization and function of MCCs in the human reproductive tracts, discuss how cilia and cilia beating-generated fluid flow directly and indirectly contribute to the processes in these organs, and how lack or improper functioning of cilia influence human fertility.

Keywords: cilia; ectopic pregnancy; efferent ductules; endometrium; fallopian tube; flagella; infertility; uterus.

Figure 1

Schematic representation of the ciliary shaft. The ultrastructure (cross-sectional views) of a typical (A) non-motile primary cilium with 9 × 2 + 0 microtubule organization and (B) motile cilium with 9 × 2 + 2 microtubule arrangement and major ciliary complexes. The red arrow indicates the level at which the cilium cross-section is depicted. In the primary cilium, the canonical 9 × 2 + 0 microtubule organization is only visible at the cilium base (cross-section 3, arrow 3). More distally, the outer doublets lose their symmetry and shift into the cilium center; additionally, one by one, the B-tubules are terminated, and the cilium diameter is reduced (cross-section 2, arrow 2). At the cilium tip (cross-section 1, arrow 1) all B-tubules and most of the A-tubules are terminated, and thus only a few singlets are visible. Note the presence of (i) network-like densities (cyan) along the whole primary cilium length, interconnecting microtubules and microtubules to a ciliary membrane (IMCD3 cell, based on images presented by [42]) or (ii) proteins (MIPs) in the A-tubule lumen, EB1-like protein between protofilaments except in the tubule seam, and F-actin (MDCK-II cell, based on [43]). For the ultrastructural organization of the entire motile cilium, transition zone, and basal body, please see [54], Figure 1.

Figure 2

Changes in the proportion of MCCs and secretory cells along the human fallopian tube. (A) Schematic representation of the cut-open fallopian tube, with fimbria surrounding a part of the ovary on one end and showing the connection to the uterus on the other end; (B–D) schematic representation of the epithelium showing the proportion of the MCCs (green) and secretory cells (blue, some with a primary cilium) in (B) fimbria and infundibulum, (C) ampulla, and (D) isthmus; (C1,D1) a scheme of the cross-section through (C1) ampulla and (D1) isthmus showing the organization of the mucosal folds; (E) schematic representation of the changes of the secretory cell apical surface (based on [119,125]).

Figure 3

Changes in the proportion of MCCs and secretory cells in the epithelium lining the inner surface of the uterus. Schematic representations of (A) uterus; (B) uterine gland; (C–E) luminal epithelium, showing the proportion of the MCCs (green) and secretory cells (blue, some with a primary cilium) during (C) proliferative phase, (D) implantation window, and (E) late secretory phase. Note flat or slightly dome-shaped secretory cells with numerous slender microvilli during the proliferative phase (C), secretory cells with a single, large, bulb-like protrusion, a pinopode, during the implantation window (D), and a secretory cell with a regressing pinopode in a secretory phase (E). Based on the SEM and TEM images [204,205,206,207].

Figure 4

Schematic representation of the epithelium composition in efferent ductules. (A). Scheme of the testis and epididymis; (B–H) schematic representation of the monolayer epithelia lining the luminal surface of the indicated parts of the reproductive tract (1–3 in image 4A) based on TEM images [264]; (1) straight tubules and initial part of the coiling fragment of the efferent ductules, image 4C; (2) efferent ductules, images 4D–G; (3) epididymis, image 4H; the reabsorptive cells (blue) with microvilli and primary cilia, MCCs (green) with numerous motile cilia (please note the changes in cell shape and height); (B) irregular epithelium composed of non-ciliated cells in rete testis, near the efferent ductule junction; (C) irregular epithelium composed of MCCs and reabsorptive cells in the straight tubule and initial part of the coiling fragment of the efferent ductules; (D) typical columnar epithelium in coiled parts of the efferent ductules; (E) cuboidal epithelium in blind-ended efferent ductules; (F) cuboidal epithelium in efferent ductules’ cavities; (G) columnar epithelium in efferent ductules, close to the junction with the epididymis; (H) columnar epithelium in epididymis composed of non-ciliated cells. ED: efferent ductules.