This study was carried out to investigate the effects of exposure to estrogen antagonist nafoxidine hydrochloride (NH) and/or melatonin (Mlt) on certain bone metabolism parameters in killifish Aphanius fasciatus, a species suggested to be a suitable model for studying spinal deformities such as scoliosis. Immature females of A. fasciatus receiving 10 μg/L NH and/or 100 μg/L of Mlt were used and were sacrificed 30 days after the treatment. The spinal column, brain, and liver were collected and analyzed by various histological, biochemical, chemical, and molecular investigations. NH exposure increased frequency of histological alterations and caused signs of spinal column demineralization such as significant decrease in the percentage of nonorganic components content and calcium concentration. These changes were accompanied by decreased alkaline phosphatase activity (AP), hepatic insulin growth factor-1 (IGF-1) content, and, interestingly, cerebral Mlt concentration. Concomitant treatment with Mlt and NH enhanced expression of the gene encoding the Mlt receptor “mtnr1aa”and significantly restored the normal skeletal histology and the normal metabolism bone parameters. Our data suggest that disturbance of estrogen pathway in A. fasciatus induces cerebral Mlt depletion and, then, causes skeletal tissue alterations and bone demineralization and that exogenous Mlt supplementation has a protective effect. Thus, estrogen receptor antagonists and Mlt become important compounds to consider for the accurate prediction and assessment of bone physiology and spinal deformities in fish.

进行这项研究的目的是研究暴露于雌激素拮抗剂盐酸萘甲氧嘧啶（NH）和/或褪黑激素（Mlt）对致死鱼类Aphanius fasciatus某些骨代谢参数的影响，该物种被认为是研究脊柱畸形的合适模型，例如脊柱侧弯。幼女性A.鲀使用接受10μg/ L NH和/或100μg/ L Mlt的溶液，并在处理30天后处死。收集脊柱，大脑和肝脏，并通​​过各种组织学，生化，化学和分子研究进行分析。氨暴露增加了组织学改变的频率，并引起了脊柱脱矿质的迹象，例如非有机成分含量百分比和钙浓度的显着降低。这些变化伴随着碱性磷酸酶活性（AP），肝胰岛素生长因子1（IGF-1）含量降低，以及脑Mlt浓度降低。Mlt和NH的同时处理增强了编码Mlt受体“ mtnr1aa”的基因的表达，并显着恢复了正常的骨骼组织学和正常的新陈代谢骨参数。A.鲀诱导脑MLT耗尽，然后，使骨骼组织改建和骨脱矿质和外源性MLT补充有保护作用。因此，雌激素受体拮抗剂和Mlt成为重要的化合物，可用于准确预测和评估鱼的骨生理和脊柱畸形。