EXPRESSION AND REGULATION OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENE IN THE FEMALE REPRODUCTIVE-TRACT

Tumour necrosis factor-alpha (TNF), a potent cytokine originally identified as a product of activated macrophages, is now known to be produced by many types of cells, and has been implicated in regulation of normal tissue homeostasis as well as in cellular differentiation. In humans and some murids, the TNF gene is expressed in ovaries, oviducts, uteri, placentas and embryos. Specific transcripts and proteins have been identified in oocytes, granulosa and theca cells, luminal and glandular epithelial cells, myometrial cells, decidual cells, placental trophoblast, macropage-like cells and embryonic skin. Both prior and subsequent to implantation, uterine TNF mRNA and protein appear in specific cell lineages in an ordered temporal sequence. This and other findings indicate that transcription of the TNF gene in the uterus is regulated either directly or indirectly by ovarian and/or placental hormones. By contrast, there is as yet no evidence for regulation of this gene by other uterine cytokines such as colony stimulating factor-1 (CSF-1). Although the functions of this pleiotrophic, multifunctional molecule are largely unknown, the findings to date are consistent with the postulate that TNF is involved in gamete development, cyclic changes in the uterus, cancers of the female reproductive tract, placental maturation and embryonic development.