Chlamydiae infect the urogenital tract and can cause infertility in woman (see chapter 1.2). Various model systems exist to study these infections. However, they can not completely simulate the complex situation of the primary tissue within organs and might lack important factors present in vivo. As primary cells and tissue of the human fallopian tube (FT) are targets of chlamydial infection, primary FT cells and FT ex vivo tissue culture were used in this study.
Introduction 1.4.1 Anatomy of the female genital tract
The female reproductive tract contains pairs of ovary and fallopian tube (also named oviduct or tuba uterina). The ovary containing the egg cells is in close proximity to the fallopian tube, which connects to the uterus and performs the task of transporting the egg into it (Fig. 1.3).
Fig. 1.3: Anatomy of the human female genital tract. The fallopian tube connects the ovary with the uterus. The ovary is held in place by the utero-ovarian ligament. The cervix protrudes into the vagina. The fallopian tube consists of four segments, which differ in width and extent of mucosal folds: the infundibulum, the ampulla, the isthmus and the pars uterina. For further description see text.
The fallopian tube comprises distinct regions varying in their structure. The infundibulum is a cone-like structure with fimbriae and an opening towards the ovary. It absorbs the egg. The ampulla is the longest part of the tube and the one with the largest lumen. The mucous inner layer, the mucosa, forms multiple folds in the ampullary region (Fig. 1.4).
The following part, the isthmus, is located close to the uterus and has a narrowed lumen (Fig. 1.5). The mucosal folds are reduced, and muscle layers are thicker than in the previous parts. The opening into the uterus lumen runs inside the uterus wall and is named pars uterina (or pars uterina tubae uterinae). The endometrium is the mucosa (see below) of the uterus. The neck of the uterus, the cervix, protrudes into the vagina (Nasu and Narahara, 2010; Saksouk and Johnson, 2004; Bucher and Wartenberg, 1997).
Introduction
Fig. 1.4: Transversal section through the ampullary region of a fallopian tube. Ampullary region of a 20-year-old woman. Extensive mucosal folds protrude into the lumen of the tube; the tubal musculature contains blood vessels; subperitoneal musculature surrounds the tube and is encircled by the tunica serosa (lining of the abdominal cavity). Drawing of hematoxillin-eosin staining. From Bucher and Wartenberg, 1997.
Fig. 1.5: Transversal section through the isthmus of a fallopian tube. Isthmic region near the uterus of a 44-year-old woman. Simple columnar epithelium lines the lumen of the tube;
the extent of mucosal folds is reduced; circular and longitudinal musculature, the two layers of tubal musculature, form thick layers. Drawing of hematoxillin-eosin staining. From Bucher and Wartenberg, 1997.
Introduction 1.4.2 Epithelia and endothelia
Epithelia are the cell layers lining all surfaces of the body. This includes the inner surfaces of organs, the internal body cavities and the mammalian skin. Epithelial cells are in close proximity to each other and form a closed cell layer. The basement membrane, a thin fibrous layer beneath the epithelial cells, anchors the basal side of the epithelium to the underlying connective tissue. The apical side of the cells faces the lumen of an organ, a body cavity or the environment (in case of skin). In addition, a specialised type of epithelium exits, named endothelium, which lines the inner surfaces of blood and lymph vessels (Bucher and Wartenberg, 1997).
Classification of epithelia is based on cell shape and number of layers. Single-layer epithelium is termed simple, whereas epithelium consisting of two or more cell layers is named stratified. According to the height of cells in the top layer, epithelia are classified as columnar (with cells taller than wide), cuboidal (with cube-like shaped cells) or squamous (with flattened cells) (Bucher and Wartenberg, 1997).
The mucosa of the human fallopian tube consists of a single-layer columnar epithelium and the connective tissue underneath (lamina propria; also named lamina propria mucosae) (Fig. 1.6). Ciliated as well as non-ciliated cells are present in the epithelial layer (Bucher and Wartenberg, 1997). The cytoskeletal intermediate filaments cytokeratin-8 and cytokeratin-18 are typically found in simple epithelium (Moll, 1993).
Fig. 1.6: Mucosa of the human fallopian tube. The mucosa of the human fallopian tube consists of a single-layer columnar epithelium (with ciliated and non-ciliated cells) and the lamina propria underneath. Drawing of hematoxillin-eosin staining. From Bucher and Wartenberg, 1997.
Polarized epithelial cells
In the body, epithelial layers form a tight barrier. The cells are polarized possessing distinct membrane compartments with differential composition: the apical membrane (AM) and the baso-lateral membrane (BLM) (Fig. 1.7). Tight junctions (TJ) are the protein complexes responsible for barrier function. They consist among others of proteins of the
Introduction
Adherens junctions mediate cell-cell-adhesion via homophilic interactions of cadherins (Fig. 1.7). These possess a transmembrane and a surface part. Cadherin-mediated contacts depend on Ca2+ interacting with the extracellular domains. E-cadherin is the form predominantly found in epithelial cells and VE-cadherin was described as vascular endothelial cadherin. The intracellular catenins connect the junctions to the actin cytoskeleton (Meng and Takeichi, 2009; Radisky, 2005).
Additional proteins mediating adherence between cells are the homophilic transmembrane proteins EpCAM (epithelial cell adhesion molecule, CD326), which is specifically expressed in epithelial cells, and PECAM-1 (platelet/endothelial cell adhesion molecule 1, CD31) in endothelial cells (Baeuerle and Gires, 2007; Woodfin, et al., 2007).
EpCAM was also described to interact directly with the tight junction protein claudin-7 as well as to antagonize cell contacts established by cadherins (Ladwein, et al., 2005;
Litvinov, et al., 1997). The contact between the basal membrane of the epithelial cells and the basement membrane is mediated by a group of transmembrane proteins, the integrins (Radisky, 2005).
Fig. 1.7: Tight and adherens junctions in polarized epithelial cells. For description see text.
AJ: adherens junction; AM: apical membrane (grey); BLM: baso-lateral membrane (dark red); BM:
basement membrane (black); N: nucleus (brown); TJ: tight junction.