Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.
Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.
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DOI：
10.2147/dddt.s75266
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Sapmaz E
中科院分区：
文献类型：
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作者：
Pala Ş;Atilgan R;Ozkan ZS;Kavak SB;Ilhan N;Akpolat N;Sapmaz E
在实验环境下，研究低至高剂量他莫昔芬对卵巢过度刺激综合征（OHSS）患者卵巢组织病理学、血清VEGF和内皮素1水平的影响。选取22日龄雌性Wistar白化大鼠20只，随机分为4组。15只大鼠连续4天皮下注射促卵泡激素10 IU，第5天皮下注射人绒毛膜促性腺激素30 IU诱导OHSS。第1组（n=5）为35日龄对照大鼠，第2组（n=5）为35日龄OHSS大鼠，第3组（n=5）为27日龄OHSS大鼠，给予1 mg/kg口服他莫昔芬7 d，第4组（n=5）为27日龄OHSS大鼠，给予3 mg/kg口服他莫昔芬7 d。第35天，所有大鼠均被斩首。测定各组大鼠血清VEGF、内皮素1和卵巢卵泡储备。采用Kruskal-Wallis方差分析和Mann-Whitney u检验进行统计比较。进行Bonferroni校正以控制显著性膨胀，显著性水平设置为p值小于0.025。尽管OHSS组血清VEGF、内皮素1、卵泡储备、黄体血管生成和纤维化水平高于对照组，但这些差异并不显著（P < 0.025， Mann-Whitney u检验）。与对照组相比，他莫昔芬组卵巢卵泡储备明显减少（P<0.025， Mann-Whitney u检验），而他莫昔芬组大鼠黄体血管生成、闭锁卵泡数量、纤维化和血清VEGF明显升高（P<0.025， Mann-Whitney u检验）。低剂量他莫昔芬组大鼠滤泡储备和纤维化明显低于高剂量他莫昔芬组（P<0.025， Mann-Whitney u检验）。各组内皮素1水平无显著变化（P < 0.025， Mann-Whitney u检验）。在我们的实验模型中，他莫昔芬1 g和3 g导致VEGF和内皮素1水平呈剂量依赖性增加，卵巢卵泡储备明显减少。
To examine the effects of low-to-high doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome (OHSS) in an experimental setting. A total of 20 female Wistar albino rats, 22 days of age, were randomly divided into four groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15 rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2 (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3 mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats. Kruskal–Wallis variance analysis and the Mann–Whitney U-test were used for statistical comparisons. A Bonferroni correction was performed to control the inflation of significance, with a significance level set at a P-value of less than 0.025. Despite higher serum VEGF, endothelin 1, follicular reserve, and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to controls, these differences were not significant (P>0.025, Mann–Whitney U-test). There was a significant reduction in the ovarian follicular reserve in tamoxifen groups compared to controls (P<0.025, Mann–Whitney U-test), while angiogenesis of the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were significantly higher in rats receiving tamoxifen (P<0.025, Mann–Whitney U-test). Also, significantly lower follicular reserve and fibrosis were observed among rats in the low-dose tamoxifen group in comparison with rats in the high-dose tamoxifen group (P<0.025, Mann–Whitney U-test). No groups had a significant change in endothelin 1 levels (P>0.025, Mann–Whitney U-test). Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and endothelin 1 levels, and ovarian follicle reserves were significantly reduced in our experimental model.