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Title: FOLLICULAR EXPRESSION OF A HUMAN BETA-CELL LEUKEMIA/LYMPHOMA-2 (BCL-2)TRANSGENE DOES NOT DECREASE ATRESIA OR INCREASE OVULATION RATE IN SWINE

Author
item Guthrie, Howard
item Wall, Robert
item PURSEL, V - 1265-85-00 COLLABORATOR
item Foster Frey, Juli
item Donovan, David
item Dawson, Harry
item Welch, Glenn
item Garrett, Wesley

Submitted to: Journal Of Reproduction, Fertility And Development
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2005
Publication Date: 4/12/2005
Citation: Guthrie, H.D., Wall, R.J., Pursel, V.G., Foster Frey, J.A., Donovan, D.M., Dawson, H.D., Welch, G.R., Garrett, W.M. 2005. Follicular expression of a human B-cell leukemia/lymphoma-2 (Bcl-2)transgene does not decrease atresia or increase ovulation rate in swine. Journal Of Reproduction, Fertility And Development. 17(4):457-468.

Interpretive Summary: Transgenic gilts (TG) producing human Bcl-2 transgene protein, a cell survival factor, were used to determine if over production of human Bcl-2 in the ovaries would inhibit the mitochondrial-dependent cell death pathway to increase the number of healthy follicles and ovulation rate. Most mature follicles in TG prepubertal and day 50 pregnant gilts, whether healthy or dying, expressed the Bcl-2 transgene protein; 86% of healthy and 54% of dying follicles. In contrast, Bcl-2 transgene protein was almost entirely absent from the ovaries of non-TG littermates (n=13). However, in spite of abundant over expression of the transgene, the frequency of dying follicles was approximately 50% both in TG and non-TG gilts and the mean ovulation rate did not differ significantly between TG (15.9) and non-TG (16.4) gilts. The molecular basis of the failure of ectopic Bcl-2 expression to increase the ratio of healthy to atretic follicles is unknown, but it is possible that the activity of the mitochondrial-dependent cell death pathway was not neutralized by over production of human Bcl-2 or that other cell death pathways compensated for the decreased mitochondrial-dependent cell death.

Technical Abstract: Transgenic gilts (TG) carrying a mouse inhibin alpha subunit promoter driving a human Bcl-2 cDNA transgene were produced and used to determine if ectopic expression of Bcl-2 in the ovaries would decrease the frequency of atresia in antral follicles and increase ovulation rate. Immunohistochemical analysis showed that the Bcl-2 transgene protein was expressed in granulosa and theca cells, in 86% of healthy and 54% of atretic follicles analyzed in TG prepubertal and day 50 pregnant gilts n=24). In contrast, Bcl-2 transgene protein was expressed in only 1.4% of healthy and 0% of atretic follicles in non-TG littermates (n=13). Real-time reverse transcriptase-polymerase chain reaction analysis confirmed that human Bcl-2 was expressed in follicles of TG gilts. The atresia rate for TG and non-TG groups did not differ (P > 0.05)for prepubertal (45 vs. 59%) and day 50 pregnant gilts(53 vs. 52%), respectively. The mean ovulation rate and SEM did not differ (P < 0.05) between TG (15.9 0.8, n = 12) and non-TG (16.4 0.6, n = 7) day 50 pregnant gilts. The molecular basis of the failure of ectopic Bcl-2 expression to increase the ratio of healthy to atretic follicles is unknown, but it is possible that the activity of the mitochondrial-dependent cell death pathway was not neutralized by ectopic expression of human Bcl-2 or that other cell death pathways compensated for the decreased mitochondrial-dependent cell death.