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Formation and Barrier Function of Tight Junctions in Human Ovarian Surface Epithelium¹

Department of Obstetrics/Gynecology³ Department of Anatomy and Cell Biology,⁴ Sahlgrenska Academy at Göteborg University, 413 45 Göteborg, Sweden

The normal ovarian surface epithelium (OSE) is a primitive epithelium made up by a single layer of mesothelial-type epithelial cells. When these cells get trapped in the ovarian stroma, expression of epithelial specific markers, such as E-cadherin, are induced. Most epithelial cells are also characterized by the ability to form tight junctions (TJ). Incomplete TJ have earlier been demonstrated in the OSE by electron microscopy studies. We have investigated expression and localization of the TJ proteins ZO-1, occludin, and claudin-1 in tissue biopsies from normal human ovaries and OSE in culture. The dynamics of TJ formation were studied in human OSE cultured on porous filters in culture inserts by measuring trans epithelial resistance (TER) including Ca²⁺ switch experiments. Confluent OSE cells were also analyzed by electron microscopy. The results show that normal human OSE has expression of all three TJ proteins investigated. These proteins, ZO-1, occludin, and claudin-1, were localized to OSE cell borders both in ovarian biopsies and in cultured OSE. There was no difference in this regard between fertile and postmenopausal women. Cells in culture were polarized and presented junctional complexes seen by electron microscopy. In the Ca²⁺ switch experiments, removing free Ca²⁺ transiently, TER decreased significantly (P < 0.05) in the Ca²⁺-free group compared with nontreated OSE. TER was fully restored after 24 h. N-cadherin but not E-cadherin was expressed in the OSE and localized to the cell borders. We conclude that normal human OSE express and form functional TJ both in vivo and vitro. This report also describes a method to study the influence of ovarian-derived mediators on TJ in cultured OSE.

¹ Supported by grants from The Swedish Medical Research Council, King Gustav V Jubilee Clinic Cancer Research Foundation and the foundations of Assar Gabrielsson, Lars Hierta, Syskonen Svensson, and the Gothenburg and Swedish Medical Societies.

² Correspondence: Karin Sundfeldt, Department of Obstetrics/Gynecology, KK-Spec. lab. Gula straket 5, SU/Sahlgrenska Hospital, SE-413 45 Goteborg, Sweden. FAX: 46 31 418717; karin.sundfeldt{at}obgyn.gu.se

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