An official journal of the Society for Biology of Reproduction and the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn

December 2013 (No. 4)

The Bax/Bcl-2 apoptotic pathway is not responsible for the increase in apoptosis in the RU486-treated rat uterus during early pregnancy

Kathrine E. Theron a,*, Clement B. Penny b, Margot J. Hosie a

a School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa

b Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa

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An increase in apoptotic activity has been observed in both the rabbit and the rat endometria following treatment with RU486. The aim of this study was to assess whether Bax and Bcl-2 signaling, in response to RU486, could be crucial role players mediating apoptosis in the rat uterus during early pregnancy. RU486 is a partial progesterone (P4) and estrogen receptor antagonist, functioning to actively silence P4 receptor gene-associated transcription. Although an increase in apoptosis as a result of RU486 administration has been previously reported in rabbits, the specific apoptotic factors and pathways involved in driving this process have not yet been established. Immunofluorescent techniques were used to deter- mine protein expression levels of both Bax and Bcl-2 in RU486-treated endometria at days 4.5, 5.5 and 6.5 of pregnancy. The Bax/Bcl-2 index was used to determine the overall pro- or anti-apoptotic setting at each day of pregnancy, following RU486 administration. Changes in the Bax and Bcl-2 gene expression levels as a consequence of RU486 administration were evaluated using RT-qPCR. Both the protein and gene expression analyses suggest that RU486 induces a change toward an overall anti-apoptotic signal within the Bax/Bcl-2 pathway. These results suggest that the observed increase in apoptosis following RU486 administration is not driven by a shift in the Bax/Bcl-2 ratio toward cell death, when the P4 and estrogen receptors are partially inactivated by RU486, but is possibly regulated by another apoptotic pathway.

Reproductive Biology 2013 13 4: 290–297.

* Corresponding author: Department of Medical Sciences, Public Health and Health Promotion, School of Health Sciences, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa (present address); E-mail address: (K.E. Theron).