Osatd-Rahimi Negar, Saburi Ehsan, Karimi Sareh, Boustan Arad, Ebrahimzadeh-Bideskan Alireza
Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2023 Feb;26(2):208-215. doi: 10.22038/IJBMS.2022.66660.14636.
Nowadays, methamphetamine (METH) abuse as a psychotropic drug is increasing. There is insufficient information about its adverse effects on the ovarian reserve of the next generation. Herein, we tried to investigate the effect of METH abuse during pregnancy and lactation and, subsequently, the therapeutic effect of melatonin on ovarian reserve in offspring.
In the present study, BALB/c pregnant female mice were divided into 3 groups: Control, Saline, and METH (5mg/Kg). METH was injected during pregnancy and lactation, and the female offspring of each group was divided into 2 subgroups: A) treated with 10 mg/kg Melatonin daily until puberty (6 weeks old) and B) received distilled water. The animals were sacrificed at 6 weeks of age, and blood samples were collected for hormonal assessments; the right ovaries were removed and fixed for TUNEL and Hematoxylin & Eosin staining, and the left ovaries were removed and stored for gene expression and oxidative stress evaluation.
In the MTEH group, two indicators of ovarian reserve (including anti-Müllerian hormone (AMH) and primordial follicle, and Cyclin D1 (CCND-1) and proliferating cell nuclear antigen (PCNA) genes expression significantly decreased, and the oxidative stress and apoptosis significantly increased in comparison with other groups. After lactation in the MTEH group, melatonin treatment significantly improved the ovarian reserve and gene expression and declined apoptosis and oxidative stress.
METH abuse during pregnancy and lactation decreased ovarian reserve in offspring. The administration of melatonin as an anti-oxidant agent after lactation can counteract the adverse effects of METH on offspring ovaries.
如今,作为一种精神药物,甲基苯丙胺(METH)的滥用情况日益增加。关于其对下一代卵巢储备的不良影响,目前的信息尚不充分。在此,我们试图研究孕期和哺乳期滥用METH的影响,以及随后褪黑素对后代卵巢储备的治疗效果。
在本研究中,将BALB/c怀孕雌性小鼠分为3组:对照组、生理盐水组和METH组(5mg/Kg)。在孕期和哺乳期注射METH,每组的雌性后代再分为2个子组:A)每天用10mg/kg褪黑素治疗直至青春期(6周龄),B)接受蒸馏水。在6周龄时处死动物,采集血样进行激素评估;取出右侧卵巢并固定用于TUNEL和苏木精-伊红染色,取出左侧卵巢并保存用于基因表达和氧化应激评估。
在MTEH组中,与其他组相比,卵巢储备的两个指标(包括抗苗勒管激素(AMH)和原始卵泡,以及细胞周期蛋白D1(CCND-1)和增殖细胞核抗原(PCNA)基因表达显著降低,氧化应激和细胞凋亡显著增加。在MTEH组哺乳期后,褪黑素治疗显著改善了卵巢储备和基因表达,并降低了细胞凋亡和氧化应激。
孕期和哺乳期滥用METH会降低后代的卵巢储备。哺乳期后给予褪黑素作为抗氧化剂可以抵消METH对后代卵巢的不良影响。