EVALUATION OF THE EFFECTS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON FEMALE REPRODUCTION IN ADULT WISTAR RATS
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Abstract
The increasing recreational use of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") among women of reproductive age raises critical concerns regarding fertility and pregnancy outcomes. This study investigated the reproductive and developmental toxicity of MDMA in adult female Wistar rats, focusing on hormonal regulation, oxidative stress, histopathology, and gestational effects following pre-gestational and gestational exposure. A total of 140 Wistar rats (120 females, 20 males) were assigned to pre-gestational (Category A) and gestational (Category B) protocols. Treated groups received oral MDMA at 80 mg/kg and 160 mg/kg, while controls received distilled water. Serum levels of FSH, LH, PRL, estradiol, progesterone, and testosterone were measured alongside oxidative stress markers (SOD, CAT, GPx, MDA) and histological analyses of the pituitary, ovaries, and uterus. Data were analyzed using one-way ANOVA with LSD post hoc test (p < 0.05).
MDMA induced dose-dependent reductions in body and reproductive organ weights, likely due to serotonergic suppression of appetite, oxidative stress, and mitochondrial dysfunction. Hormonal assays revealed significant disruption of the hypothalamic-pituitary-gonadal (HPG) axis, including reduced LH (p = 0.02), elevated estradiol (p = 0.00), and progesterone (p = 0.05). A biphasic testosterone response was observed: reduced in the 80 mg/kg group (0.48 ± 0.00 ng/mL vs. 1.12 ± 0.14 ng/mL in controls) and elevated in the 160 mg/kg group (1.48 ± 0.09 ng/mL; p = 0.00), suggesting dysregulation of androgen synthesis via theca cell dysfunction or disrupted HPG feedback. Reproductive outcomes mirrored endocrine alterations. Pre-gestational exposure reduced conception rates (100% in controls vs. 20% and 0% in treated groups). Gestational exposure impaired implantation, fetal viability, and growth, leading to increased resorptions, intrauterine growth restriction, stillbirths, and postnatal abnormalities. Biochemical assays revealed dose-dependent suppression of antioxidant enzymes and altered lipid peroxidation, indicating oxidative damage in ovarian and uterine tissues.
Histopathological evaluation showed progressive degeneration: the pituitary exhibited chromophobe predominance and vacuolation; ovaries showed follicular atresia, degeneration, and vascular injury; and uterine tissues demonstrated glandular atrophy, edema, inflammation, and myometrial disruption. These structural changes aligned with the observed biochemical and hormonal abnormalities. In conclusion, MDMA exposure before or during pregnancy disrupts female reproductive function in a dose-dependent manner. It impairs fertility, alters endocrine signaling, induces oxidative stress, and causes tissue-specific toxicity, with profound consequences for implantation and fetal development. These findings reinforce the public health risks of MDMA use during reproductive years and the need for targeted reproductive toxicology awareness.
MDMA induced dose-dependent reductions in body and reproductive organ weights, likely due to serotonergic suppression of appetite, oxidative stress, and mitochondrial dysfunction. Hormonal assays revealed significant disruption of the hypothalamic-pituitary-gonadal (HPG) axis, including reduced LH (p = 0.02), elevated estradiol (p = 0.00), and progesterone (p = 0.05). A biphasic testosterone response was observed: reduced in the 80 mg/kg group (0.48 ± 0.00 ng/mL vs. 1.12 ± 0.14 ng/mL in controls) and elevated in the 160 mg/kg group (1.48 ± 0.09 ng/mL; p = 0.00), suggesting dysregulation of androgen synthesis via theca cell dysfunction or disrupted HPG feedback. Reproductive outcomes mirrored endocrine alterations. Pre-gestational exposure reduced conception rates (100% in controls vs. 20% and 0% in treated groups). Gestational exposure impaired implantation, fetal viability, and growth, leading to increased resorptions, intrauterine growth restriction, stillbirths, and postnatal abnormalities. Biochemical assays revealed dose-dependent suppression of antioxidant enzymes and altered lipid peroxidation, indicating oxidative damage in ovarian and uterine tissues.
Histopathological evaluation showed progressive degeneration: the pituitary exhibited chromophobe predominance and vacuolation; ovaries showed follicular atresia, degeneration, and vascular injury; and uterine tissues demonstrated glandular atrophy, edema, inflammation, and myometrial disruption. These structural changes aligned with the observed biochemical and hormonal abnormalities. In conclusion, MDMA exposure before or during pregnancy disrupts female reproductive function in a dose-dependent manner. It impairs fertility, alters endocrine signaling, induces oxidative stress, and causes tissue-specific toxicity, with profound consequences for implantation and fetal development. These findings reinforce the public health risks of MDMA use during reproductive years and the need for targeted reproductive toxicology awareness.
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