The effect of chronic and acute exercise on thymocyte apoptosis and necrosis in ovariectomized mice given dietary genistein.

AIM: At menopause, many women consume phytoestrogens instead of beginning hormone replacement therapy. Many also start exercise programs for health benefits. Genistein, a soy isoflavone with estrogen-like properties, induces lymphocyte apoptosis in vitro. Aerobic exercise also induces apoptosis in lymphoid cells. The present study was designed to determine the effect of chronic (wheel running, WR) and acute (treadmill) exercise on in vivo apoptosis of thymocytes using an animal model of menopause with supplementation from dietary genistein. METHODS: Using a randomized design, 99 ovariectomized B6D2F1 mice were fed 250 (GEN) or 0 (C) ppm genistein and given concurrent exercise (voluntary wheel running-WR; or WR followed by a bout of high intensity treadmill running-WR+TREAD) or remained sedentary (SED). After 21 days, mice were sacrificed for measurements of body weights, tissue weights, thymocyte apoptosis and necrosis by annexin-V FITC and propidium iodide staining and flow cytometry, DNA fragmentation by ELISA, and plasma estrogen concentrations by RIA. RESULTS: WR+TREAD mice had lower percentages of viable and higher percentages of apoptotic and necrotic cells from thymus compared with SED or WR conditions (p<0.001). WR resulted in greater DNA fragmentation in thymus cell lysates than in samples from SED mice (p<0.005). There were no differences in thymocyte apoptosis or DNA fragmentation between GEN and C mice, either independently or interactively with exercise. GEN mice tended to have greater wheel running activity than C mice (0.05

Effect of 17beta-estradiol and voluntary exercise on lymphocyte apoptosis in mice.

During the perimenopause, women may begin estrogen replacement therapy (ERT) and physical activity programs to reduce the symptoms of the climacteric. High-intensity exercise increases lymphocyte apoptosis, and estrogen is also known to have immune modulatory effects. The present study determined whether (1) estrogen exposure in vivo, and (2) low-intensity, voluntary exercise affect thymic and splenic lymphocyte apoptosis in adult female mice. 'Middle-aged' (>1 year), ovarian-intact female B6D2F(1) mice were implanted with 17beta-estradiol (E) pellets (L: 3 microg/day or H: 12 microg/day) or placebo (P: 0 microg/day). Mice were given 1 week to recover from implantation surgery after which they were randomized to wheel-running or no-wheel-running conditions. Twenty one days later, mice were sacrificed and thymus and spleen removed for determination of percent apoptosis and percent necrosis by flow cytometry, serum E levels by RIA, and tissue and body weights. Estrogen-treated, ovarian-intact mice accumulated less cumulative wheel-running activity than mice implanted with placebo (P<.001). E exposure was associated with lighter thymuses (P<.05), higher thymocyte apoptosis (P<.001), and higher serum E levels (P<.001), effects which were not modified by voluntary exercise. In contrast, splenocyte apoptosis and spleen weights did not differ by estrogen treatment or exercise. The results suggest that in vivo exposure to supplemental estrogen is associated with greater spontaneous apoptosis of thymocytes and reduced thymus weights in older ovarian-intact mice. The clinical significance for thymic (cellular) immunity in perimenopausal women given HRT remains to be determined.