Endocrine Abstracts

Long-lasting and/or delayed reproductive effects of developmental exposure to mixtures of environmental chemicals were investigated in rats. Wistar rats were exposed to mixtures of estrogenic or anti-androgenic endocrine disrupters in pregnancy and lactation, and effects in offspring at 12–18 months of age were studied. The mixture included 13 estrogenic and anti-androgenic chemicals, including phthalates, pesticides, u.v.-filters, bisphenol A, butylparaben and paracetamol, and the mixture ratio was chosen to reflect high end human intakes. In the animal study, two groups received exposures of 150 and 450 times high end human intake levels of these chemicals combined, and one group received a mixture including only the anti-androgens.

Females exposed to the mixture showed earlier reproductive aging, and males had reduced epididymal sperm count, histological changes in the epididymis, and normal prostatic aging (atrophy) was altered towards hyperplasia. A possible increased incidence of pituitary adenomas in the mixture groups could be related to the altered age of reproductive senescence.These effects were mainly attributed to the anti-androgenic compounds in the mixture, as comparable effects were in most cases seen in animals exposed to the total mixture and in the group receiving a mixture of anti-androgens only. A previous publication describes endocrine disrupting in prepubertal offspring (Christiansen et al.. Int J Androl 2012 35 (3) 303–316), and these early findings can be a signal of severe adverse effects later in life.

This study demonstrated that developmental exposure of rats to endocrine disrupters can induce long-lasting effects manifested in early reproductive senescence, and perinatal programming of the hypothalamo-pituitary–gonadal axis may account for the observed changes in the timing of aging-related events.