Department of Dynamic and Clinical Psychology, Sapienza University of Rome and Research Center in Neurobiology Daniel Bovet" (CRiN), Rome, Italy.
Department of Psychology, Sapienza University of Rome, Rome, Italy.
J Cell Physiol. 2019 Jun;234(6):9387-9398. doi: 10.1002/jcp.27623. Epub 2018 Oct 14.
Mice exposed to continuous light undergo functional and histological changes that mimic those of human Polycystic Ovary Syndrome (PCOS). We herein induced the syndrome by exposing 30-day-old females to 10 weeks of permanent light. Ovarian morphology and histology, as well as reproductive parameters (time of observed pregnancy/delivery) were investigated. Ovaries of PCOS-modeled mice showed lack of tertiary follicles and corpora lutea, altered ovarian architecture, and increased thickness of the theca layer. When mice were returned to a normal light-dark regimen for 10 days, a slight, spontaneous improvement occurred, whereas a quick and almost complete recovery from PCOS signs and symptoms was obtained by treating animals with a daily supplementation of 420 mg/kg myo-inositol and D-chiro-inositol (MyoIns/DCIns) in a 40:1 molar ratio. Namely, ovaries from mice treated by this protocol recovered normal histological features and a proper ratio of theca/granulosa cell layer thickness (TGR), suggesting that the androgenic phenotype was efficiently reversed. Indeed, we identified TGR as a useful index of PCOS, as its increase in PCOS-modeled mice correlated linearly with reduced reproductive capability ( r = 0.75, p < 0.0001). Mice treated with a 40:1 formula regained low TGR values and faster recovery of their fertility, with a physiological delivery time after mating. On the other hand, a higher D-chiro-inositol treatment formula, such as MyoIns versus DCIns 5:1, was ineffective or even had a negative effect on clinical-pathological outcomes.
持续光照会使小鼠发生功能和组织学变化，这些变化类似于人类多囊卵巢综合征（PCOS）。我们通过让 30 日龄雌性小鼠接受 10 周的持续光照来诱导该综合征。研究了卵巢形态和组织学以及生殖参数（观察到怀孕/分娩的时间）。PCOS 模型小鼠的卵巢缺乏三级卵泡和黄体，卵巢结构发生改变，并且囊外膜层厚度增加。当小鼠恢复正常的明暗周期 10 天时，会出现轻微的自发改善，而通过每天补充 420mg/kg 肌醇和 D-手性肌醇（MyoIns/DCIns）以 40:1 的摩尔比治疗动物，则可以快速且几乎完全从 PCOS 症状和体征中恢复。即，用该方案治疗的小鼠的卵巢恢复了正常的组织学特征和适当的囊外膜/颗粒细胞层厚度比（TGR），表明雄激素表型得到了有效逆转。事实上，我们发现 TGR 是 PCOS 的一个有用指标，因为 PCOS 模型小鼠的 TGR 增加与生殖能力降低呈线性相关（r=0.75，p<0.0001）。用 40:1 配方治疗的小鼠 TGR 值较低，并且更快地恢复生育能力，在交配后具有生理分娩时间。另一方面，更高的 D-手性肌醇治疗配方，如 MyoIns 与 DCIns 5:1，对临床病理结果无效甚至有负面影响。
