Long-term effects of methamphetamine exposure in adolescent mice on the future ovarian reserve in adulthood

• The long-term abuse of methamphetamine in the adolescent period causes mitochondrial damage in murine female ovarian tissue.
• The long-term abuse of methamphetamine in the adolescent period activates the Bcl-2 and Bax apoptosis signaling pathways and leads to a decrease of anti-Mullerian hormone expression in the ovary.
• Adolescent MA abuse results in a reduction of the ovarian follicle pool.

Currently, there is an increasing prevalence of adolescent exposure to methamphetamine (MA). However, there is a paucity of information concerning the long-term impact of early exposure to MA upon female fertility and ovarian reserve. The aim of this study was to investigate the effect of long-term MA exposure in adolescents on their ovarian reserve in adulthood. Adolescent mice received intraperitoneal injections of MA (5 mg/kg, three times per week) or saline from the 21st postnatal day for an 8 week period. Morphological, histological, biochemical, hormonal and ethological parameters were evaluated. An impaired ovarian reserve and vitality was found in the group treated with MA, manifesting in morphological-apparent mitochondrial damage, an activated apoptosis pathway in the ovarian tissue, a downward expression of ovarian anti-Mullerian hormone (AMH), a decreased number of primordial and growing follicles, an increased number of atretic follicles, and a depressed secretion of AMH, estradiol and progesterone from granulosa cells. However, no significant difference was noticed regarding the estrous cycle, the mating ability and the fertility outcome in the reproductive age of the mice after a period of non-medication. The present results confirmed that a long term exposure to methamphetamine in adolescent mice does have an adverse impact on their ovarian reserve, which indicates that such an early abuse of MA might influence the fertility lifespan of the female mouse.