EFFECT OF DECIDUALIZATION ON THE EXPRESSION OF BAX AND BCL-2 IN THE RAT UTERINE ENDOMETRIUM

During early pregnancy, the uterine endometrium responds to an implant ing blastocyst with the extensive growth and differentiation of decidu alization. This transformation of endometrial stromal cells begins in the antimesometrial side of the uterus to form a primary decidual zone , expands to form a secondary zone in the antimesometrium, and eventua lly transforms stromal cells in the mesometrial region. During pregnan cy, both decidual zones regress by apoptosis, leaving decidual cells i n the mesometrial region to form decidua basalis and the mature placen ta. Molecular mechanisms controlling cell death during blastocyst impl antation and decidualization are unknown. We examined the hypothesis t hat progesterone and estrogen control of endometrial differentiation a nd eventual apoptosis involves control of bcl-2 gene family expression . Ovariectomized rats were primed with estradiol and treated with prog estin (medroxyprogesterone acetate, 3.5 mg) and estradiol (200 ng) bef ore an intrauterine stimulus to initiate decidualization. Expression o f the two bax messenger RNA transcripts, 1.0 and 1.5 kilobases, was ex amined by Northern blot analysis after hormone treatment and deciduali zation, and only the 1.0-kilobase transcript was induced. After the sa me treatments, the expression of bcl-2, a suppressor of apoptosis, dec reased. In situ analysis revealed a cell type-specific increase in bax expression after the hormonal treatment and decidualization. This inc rease was first seen in luminal and glandular epithelial cells and the n in the periluminal stroma 24 h after intrauterine stimulation, with eventual progressive expression throughout the stroma. Expression of b cl-2 decreased after hormone treatment and decidualization. Immunohist ochemical studies of Bax showed that expression of Bax protein accompa nied decidualization of the stroma. Bcl-2 protein was only seen in the luminal and glandular epithelia, and its level decreased as deciduali zation progressed. These data indicate that the balance between bax an d bcl-2 expression is altered during stromal cell differentiation. Inc reased expression of bax precedes nucleosomal DNA fragmentation and ev entual apoptosis, which plays a significant role in placental developm ent.