The environmental endocrine disruptor, bisphenol A (BPA), found in plastics and thermal printer paper, is a xenoestrogen that affects steroid receptor signalling and synthesis and may contribute to the increasing incidence of disorders of sex development (DSDs) in vertebrates. The study investigated the effects of BPA on testicular differentiation in the tammar wallaby (Macropus eugenii), a marsupial whose young are born before gonadal sex differentiation (1).
Pouch young were orally treated daily with BPA (50 µg/kg) from day 0-10 postpartum (pp) (covers early male gonadal differentiation window) and collected at day 10. Another group was treated from day 20-40 pp during the male programming window (2) and sampled at day 40 pp. A third group was treated daily with fulvestrant, an estrogen receptor degrader, (1 mg/kg) between day 20-90 pp and examined at day 150 pp during urethral closure.
BPA treatment from day 0-10 pp decreased the number of SOX9-positive Sertoli cells and blocked its nuclear translocation in testes. BPA treatment from day 20-40 pp significantly decreased the number of Sertoli cells in the seminiferous tubules and also significantly downregulated the expression of genes that are important in regulating Leydig cell differentiation (DHH and PTCH1), Sertoli cell differentiation (SOX9) and androgen synthesis (STAR, CYP17A1 and POR). These data suggest that the xenoestrogen BPA interferes tammar testicular differentiation consistent with previous studies (3-5). Fulvestrant treatment downregulated 17βHSD3 expression, the gene for a key enzyme that converts androstenedione to testosterone and together with 3α-HSD, converts androsterone to dihydrotestosterone (2), suggesting that estrogen signalling might be important in maintaining androgen synthesis during testicular differentiation, as shown previously (4-5). We conclude that these results are due to the interference with the balance of androgen and oestrogen in developing male pouch young.