Department of Histology and Embryology, School of Medicine, Akdeniz University, Campus, 07070, Antalya, Turkey.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
J Assist Reprod Genet. 2019 Oct;36(10):2181-2189. doi: 10.1007/s10815-019-01560-4. Epub 2019 Aug 17.
Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI). The unique pathophysiology of classic galactosemia, with a severely reduced follicle pool at an early age, requires a new therapeutic approach. This study evaluated the effect of dehydroepiandrosterone (DHEA) on ovarian tissue in a galactose-induced POI rat model.
Pregnant rats were fed with either a normal or a 35% galactose-containing diet from day 3 of conception continuing through weaning of the litters. Galactose-exposed female offspring were further divided into 5 groups on PND21. The first group received no application. Treatment groups were fed orally by gavage once daily with sesame oil (group 2), or DHEA at doses of 0.1 mg/kg (group 3), 1 mg/kg (group 4) or 10 mg/kg (group 5) until PND70. Fertility rates of mothers with galactosemia, body weights (BWs), and ovarian weights of the litters from PND21 to PND70 were recorded. Ovarian follicle count, immunohistochemistry for proliferation and apoptosis marker expressions and TUNEL for cell death assessment were performed in offspring ovaries.
Decreased fertility, ovarian/body weights were observed under galactosemic conditions, together with decreased follicle number and increased atresia. Improved postnatal development, primordial follicle recruitment and follicular growth were observed after DHEA treatment. After DHEA treatment, the expression of Ki67 protein was found to be increased; elevated expression of cleaved-caspase-3 under galactosemia was found to be reduced.
Our data suggests that DHEA treatment may be a potentially useful clinical therapy to improve ovarian ageing in women with POI-induced by galactosemia.
几乎所有经典型半乳糖血症女性患者都会出现原发性卵巢功能不全（POI）。经典型半乳糖血症的独特病理生理学特点是卵泡池在早期严重减少，这需要一种新的治疗方法。本研究评估了脱氢表雄酮（DHEA）对半乳糖诱导的 POI 大鼠模型卵巢组织的影响。
妊娠大鼠从受孕第 3 天开始连续喂食正常或 35%含半乳糖饮食，直至断奶。半乳糖暴露的雌性后代在 PND21 时进一步分为 5 组。第一组不做任何处理。治疗组每天通过灌胃口服芝麻油（第 2 组），或 DHEA 剂量为 0.1mg/kg（第 3 组）、1mg/kg（第 4 组）或 10mg/kg（第 5 组），直至 PND70。记录半乳糖血症母亲的受孕率、体重（BW）和 PND21 至 PND70 后代的卵巢重量。对后代卵巢进行卵泡计数、增殖和凋亡标志物表达的免疫组织化学检测以及细胞死亡评估的 TUNEL 检测。
在半乳糖血症条件下，观察到受孕率、卵巢/体重降低，同时卵泡数量减少，闭锁增加。DHEA 治疗后观察到产后发育、原始卵泡募集和卵泡生长改善。DHEA 治疗后，Ki67 蛋白表达增加；半乳糖血症时 cleaved-caspase-3 的表达升高。
我们的数据表明，DHEA 治疗可能是一种有潜力的临床治疗方法，可改善半乳糖血症引起的 POI 女性的卵巢衰老。
