Alternatively Spliced Variants of Gallus gallus TNFRSF23 Are Expressed in the Ovary and Differentially Regulated by Cell Signaling Pathways1

Abstract

As a result of searching recently available chicken (ch) expressed sequence tag databases, a new Tumor Necrosis Factor Receptor Super Family (TNFRSF) member with similarity to the murine (m) TNFRSF23 decoy receptor (DcR) has been identified. However, by comparison with the mTNFRSF23, there exist at least two splice variants of chTNFRSF23, one of which includes an intracellular death domain (TNFRSF23.v1) characteristic of death receptors, and the other with a truncated cytoplasmic domain of a DcR (named TNFRSF23.v2). These two splice variants of chTNFRSF23 display differential patterns of mRNA expression across various hen tissues, with the highest levels observed within reproductive tissues. More specifically, TNFRSF23.v1 is most highly expressed in preovulatory follicle granulosa cells in the ovary, whereas TNFRSF23.v2 mRNA is found at highest levels in ovarian stromal tissue. Primary culture experiments with granulosa cells determined that expression of TNFRSF23.v1 mRNA was decreased by protein kinase A signaling and enhanced by transforming growth factor (TGF) alpha treatment. Interestingly, TGFbeta1 and signaling via protein kinase C also enhanced levels of TNFRSF23.v1 expression but only in undifferentiated granulosa cells from prehierarchal follicles. Based on patterns of mRNA expression and its endocrine/paracrine regulation, we predict that ovarian chTNFRSF23 represents a modulator of granulosa cell survival and/or differentiation. Finally, the characterization of these receptor variants is of considerable interest from an evolutionary perspective in that they provide additional evidence to support a continuing divergence of TNFRSF members throughout vertebrate evolution.

Oocyte-somatic cells interactions, lessons from evolution

“…Decoy TNF receptors have the ability to bind TNF ligands without inducing cell death. Interestingly, alternatively spliced variants of Tnfrsf23 are expressed in the chicken ovary [46] and a decoy TNF receptor was found to be differentially expressed in the fish ovary during final oocyte maturation [47]. An increased expression of a set of genes, including sphingomyelin synthase 1 (Sgms1), syntaxin 1A (Stx1a), and Pacsin3, which are implicated to a different extent in exo/endocytosis and protein trafficking, was also observed in our study, particularly at C2 stage (Figure 4).…”

Changes in the expression of interleukin-1β and lipopolysaccharide-induced TNF factor in the oviduct of laying hens in response to artificial insemination

“…Therefore, less exposure of IL1B and TNF-related molecules to sperm in the UVJ of the hen oviduct may be significant for sperm survivability. Recently, mRNA expression of IL1B, LITAF, and the TNF receptor superfamily was reported in the ovary and oviduct of laying hens, suggesting the involvement of these cytokines in the process of avian reproductive functions (Birdgham & Johnson 2004, Subedi et al 2007, Sundaresan et al 2007a, 2007b. However, the physiological significance of IL1B and TNF-related molecules in the avian oviduct, particularly in relation to the voidance of sperm from the vagina, is not fully understood.…”

Tumor necrosis factor-related apoptosis inducing ligand expression and activity in hen granulosa cells

“…Evidence from hen granulosa cells has been provided both for the apoptosis initiated following activation of the intrinsic cell death pathway , and for the attenuation of apoptosis via intracellular anti-apoptotic proteins, such as Bcl-x , the cIAP1 ortholog, inhibitor of T-cell apoptosis (ITA) (Johnson et al 1998), and survivin . No less than four TNFRSF members that contain an intracellular DD are expressed by hen granulosa cells, including Fas (TNFRSF6; , TNFR1 (TNFRSF1; ), TNFRSF23 (Bridgham & Johnson 2004), and the putative ortholog to mammalian DR5 (TNFRSF10B; . Nevertheless, in the hen, only TNFa has been demonstrated thus far to induce granulosa cell death, and only in undifferentiated granulosa from prehierarchal follicles .…”