Kumar Vikash, Kumar Rahul, Gurusubramanian Guruswami, Rathore Saurabh Singh, Roy Vikas Kumar
Department of Biotechnology, Mahatma Gandhi Central University, Motihari, Bihar, 845401, India.
Department of Zoology, Mizoram University, Aizawl, Mizoram, 796 004, India.
Mol Biol Rep. 2025 Mar 13;52(1):308. doi: 10.1007/s11033-025-10423-4.
Di (2-ethylhexyl) phthalate (DEHP), a widely used chemical in plastics, has various health hazards when accumulated in the environment. DEHP has been shown to cause toxicity to various organs like the liver, kidney, and reproductive organs. Phytocompounds have been used to mitigate DEHP-mediated organ toxicity. Morin hydrate (MH), a phytocompound, has also been known to protect tissue and organs against various induced toxic conditions. However, the impact of MH treatment on DEHP-induced uterine dysfunction has not yet been still investigated. Therefore, the present study has investigated the impact of MH on uterine physiology and morphology of DEHP-intoxicated mice.
Twenty Swiss mice were randomly divided into four groups (n = 5): control (CN), Di (2-ethylhexyl) phthalate (DP) (500 mg/kg), Di (2-ethylhexyl) phthalate (DP) + Morin hydrate (MH) (10 mg/kg), and Di (2-ethylhexyl) phthalate (DP) + Morin hydrate (MH) (100 mg/kg) for 14 days.
Our results showed that the expression of active caspase-3 was up-regulated, and Bcl2 was down-regulated in the uterus of DEHP-treated mice. Furthermore, the uterine histology also showed decreased luminal epithelium height and endometrium thickness in the DEHP-treated mice; however, myometrium layer (outer and inner) thickness was higher in DEHP-treated mice. The uterus of DEHP-treated mice also exhibited elevated oxidative stress and fibrosis, along with decreased estrogen levels and expression of estrogen receptors (ERs). MH treatment at both doses (10 and 100 mg/kg) suppressed DEHP-induced uterine apoptosis (increased Bcl2 and decreased active caspase-3 expression) and fibrosis. MH also increased the circulating estrogen levels at both doses; Further ERα and ERβ expression were elevated in the MH treated in both groups). The levels of oxidative stress malondialdehyde (MDA levels) were higher in the uterus of DEHP alone and DEHP plus MH-treated mice (100 mg/kg). Moreover, the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase (Gpx and SOD) did not show a dose-dependent response to MH treatment; rather, MH showed a differential effect on these enzymes. The elevated oxidative stress in 100 mg/kg MH treated uterus, despite elevated Gpx and SOD, remains unclear. Thus, these results suggest that MH ameliorates DEHP-induced uterine fibrosis, apoptosis, and histoarchitecture through ER modulation.
These findings suggest that MH improves uterine structure and function in DEHP-treated mice.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种在塑料中广泛使用的化学物质，在环境中积累时具有多种健康危害。已表明DEHP会对肝脏、肾脏和生殖器官等各种器官产生毒性。植物化合物已被用于减轻DEHP介导的器官毒性。水合桑色素（MH）作为一种植物化合物，也已知能保护组织和器官免受各种诱导的毒性条件影响。然而，MH治疗对DEHP诱导的子宫功能障碍的影响尚未得到研究。因此，本研究调查了MH对DEHP中毒小鼠子宫生理和形态的影响。
将20只瑞士小鼠随机分为四组（n = 5）：对照组（CN）、邻苯二甲酸二（2-乙基己基）酯（DP）（500 mg/kg）、邻苯二甲酸二（2-乙基己基）酯（DP）+水合桑色素（MH）（10 mg/kg）和邻苯二甲酸二（2-乙基己基）酯（DP）+水合桑色素（MH）（100 mg/kg），持续14天。
我们的结果表明，在DEHP处理的小鼠子宫中，活性半胱天冬酶-3的表达上调，而Bcl2下调。此外，子宫组织学还显示，DEHP处理的小鼠管腔上皮高度和子宫内膜厚度降低；然而，DEHP处理的小鼠子宫肌层（外层和内层）厚度更高。DEHP处理的小鼠子宫还表现出氧化应激和纤维化升高，同时雌激素水平和雌激素受体（ERs）表达降低。两种剂量（10和100 mg/kg）的MH处理均抑制了DEHP诱导的子宫凋亡（Bcl2增加，活性半胱天冬酶-3表达降低）和纤维化。MH在两种剂量下还增加了循环雌激素水平；此外，两组MH处理组中ERα和ERβ表达均升高。单独DEHP处理组以及DEHP加MH处理组（100 mg/kg）小鼠子宫中的氧化应激丙二醛（MDA水平）较高。此外，抗氧化酶过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶（Gpx和SOD）对MH处理未表现出剂量依赖性反应；相反，MH对这些酶表现出不同的影响。尽管Gpx和SOD升高，但100 mg/kg MH处理的子宫中氧化应激升高的原因仍不清楚。因此，这些结果表明，MH通过ER调节改善DEHP诱导的子宫纤维化、凋亡和组织结构。
这些发现表明，MH可改善DEHP处理小鼠的子宫结构和功能。
