Please cite this article as: Jääskeläinen, M., Prunskaite-Hyyryläinen, R., Naillat, F., Parviainen, H., Anttonen, M., Heikinheimo, M., Liakka, A., Ola, R., Vainio, S., Vaskivuo, T.E., Tapanainen, J.S., WNT4 is Expressed in Human Fetal and Adult Ovaries, and Its Signaling Contributes to Ovarian Cell Survival, Molecular and Cellular Endocrinology (2008), doi:10.1016/j.mce.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Of eight million oocytes formed in fetal ovaries, only 400 are ovulated and the rest are degraded via apoptosis. Studies in rodents suggest an important role for Bok and Bcl-X(L) in ovarian apoptosis, but their expression patterns and roles in human ovaries are not well known. Protein expression of Bok and Bcl-X(L) as well as the death pathway effectors TNF and caspase-3 were determined in an important collection of samples consisting of human fetal and adult ovaries. A penetrant expression of Bok, Bcl-X(L), TNF and full length and cleaved caspase-3 were characterized in fetal ovaries, with specific patterns in oocytes and pre-granulosa/granulosa cells. Bok and Bcl-X(L) were detected also in adult ovaries. Lentiviral shRNA delivery demonstrated that loss of Bok markedly reduces vulnerability to apoptosis and, conversely, loss of Bcl-X(L) increases apoptosis in human granulosa tumour cell line. The results suggest important roles for Bok and Bcl-X(L) in human ovarian development, follicle maturation and apoptosis.