Özcan Pınar, Fıçıcıoğlu Cem, Kizilkale Ozge, Yesiladali Mert, Tok Olgu Enis, Ozkan Ferda, Esrefoglu Mukaddes
Department of Obstetrics and Gynecology, Bezmialem University Faculty of Medicine, İstanbul, Turkey.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
J Assist Reprod Genet. 2016 Sep;33(9):1223-30. doi: 10.1007/s10815-016-0751-z. Epub 2016 Jun 3.
We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage.
Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed.
RESULT(S): The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03).
CONCLUSION(S): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.
我们研究了补充辅酶Q10对预防氧化应激(OS)诱导的卵巢损伤的抗氧化作用,并评估这种补充对OS相关DNA损伤的保护作用。
将24只成年雌性Sprague-Dawley大鼠随机分为三组(每组8只):第1组(对照组):腹腔注射和口服生理盐水;第2组(顺铂组):腹腔注射顺铂,4.5mg/kg,间隔7天注射两次;第3组(顺铂+辅酶Q10组):腹腔注射顺铂,4.5mg/kg,间隔7天注射两次,在顺铂注射前24小时,每天口服150mg/kg,溶于1mL生理盐水中,共14天。评估血清抗苗勒管激素(AMH)浓度、AMH阳性卵泡数量、8-羟基脱氧鸟苷(8-OHdG)免疫反应强度评估、卵巢中原始卵泡、窦卵泡和闭锁卵泡计数。
第1、2、3组的平均血清AMH浓度分别为1.3±0.19、0.16±0.03和0.27±0.20ng/mL(p<0.01)。与第2组和第3组相比,第1组的血清AMH水平显著更高(分别为p<0.01和p=0.01)。各组之间AMH阳性卵泡计数存在统计学显著差异(p<0.01)。与第2组相比,第1组显示出更多的AMH阳性颗粒细胞(p=0.01)。三组之间的原始卵泡、闭锁卵泡和窦卵泡计数存在显著差异(分别为p<0.01、p<0.01和p<0.01)。与顺铂组相比,顺铂加辅酶Q10组的闭锁卵泡计数显著更低(p<0.01)。与顺铂组相比,顺铂加辅酶Q10组的窦卵泡计数显著更高(p<0.01)。各组之间抗8-OHdG阳性卵泡的染色强度存在统计学显著差异(p=0.02)。与第2组相比,第1组抗8-OHdG阳性卵泡的染色强度显著更低(p=0.03)。
补充辅酶Q10可能通过抵消线粒体卵巢衰老和生理性程序性卵巢衰老来保护卵巢储备,尽管氧化应激在女性不孕症中的具体作用尚不清楚。