Administration of Oral Contraceptives Could Alleviate Age-Related Fertility Decline Possibly by Preventing Ovarian Damage in a Mouse Model
Administration of Oral Contraceptives Could Alleviate Age-Related Fertility Decline Possibly by Preventing Ovarian Damage in a Mouse Model
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DOI：
10.1177/1933719117746758
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发表时间：
2018-09-01
影响因子：
2.9
通讯作者：
Kurihara, Hiroki
中科院分区：
文献类型：
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作者：
Isono, Wataru;Wada-Hiraike, Osamu;Kurihara, Hiroki
排卵相关的生育能力下降被假设主要是由于卵泡的自发衰竭和退化，并且排卵周期导致的卵巢组织损伤的积累可能在该过程中起作用。在这项研究中，我们假设抑制排卵会对年龄相关的生育能力下降产生保护作用。为了验证这一假设，我们建立了一个小鼠模型，其中口服避孕药（OC）每天给药。雌性C57 BL/6 N小鼠从2月龄至12月龄每天给予OC作为排卵抑制小鼠模型。通过计算卵巢刺激后的卵母细胞数量和交配后检查活胎来研究小鼠的生殖力。我们发现，与仅给予载体的对照小鼠相比，给予用于治疗人类的2倍剂量OC的12月龄小鼠在卵巢刺激后表现出显著更高的平均卵母细胞数量（8.5 +/-0.6 vs 5.9 +/-0.6，P <0.01）。此外，与对照组相比，给予OC的12月龄小鼠交配后带活胎的自发受孕显著增加（6.0 +/- 1.2 vs 0.4 +/- 0.3，P <0.01）。在小鼠卵巢组织的组织学检查中，我们没有检测到卵泡数量的显著差异，但在施用OC的老龄小鼠中检测到棕色泡沫状纤维组织的量减少，这可能反映了卵巢组织的损伤。这些结果表明，长期服用OC可能会缓解与年龄相关的生育能力下降，其改善机制可能是通过抑制排卵来预防卵巢组织损伤。
Age-related fertility decline is hypothesized to occur mainly by the spontaneous exhaustion and deterioration of the ovarian follicle, and the accumulation of ovarian tissue damage resulting from the ovulation cycle may play roles in the process. In this study, we hypothesized that suppressing ovulation would exert protective effects against age-related fertility decline. To test this hypothesis, we established a mouse model in which oral contraceptives (OCs) were administered daily. Female C57BL/6N mice were administered OCs daily from the age of 2 months to 12 months as an ovulation suppression mouse model. Mouse fecundity was investigated by counting oocyte number after ovarian stimulation and by examining live fetuses after mating. We found that compared with control mice administered vehicle alone, 12-month-old mice administered 2-fold dose OCs used for treating humans exhibited a significantly greater average oocyte number after ovarian stimulation (8.5 +/- 0.6 vs 5.9 +/- 0.6, P < .01). In addition, spontaneous conception with living fetuses after mating was strikingly increased in 12-month-old mice administered OCs relative to controls (6.0 +/- 1.2 vs 0.4 +/- 0.3, P < .01). In the histological examination of mouse ovarian tissues, we did not detect a significant difference in ovarian follicle number, but reduced amount of brownish foamy fibrous tissues, which might reflect ovarian tissue damage, was detected in aged mice administered OCs. These results suggest the possibility that long-term OC administration might alleviate age-related fertility decline, and the improvement mechanism could be attributed to the prevention of ovarian tissue damage by suppressing ovulation.