Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Endocrine disruption in utero affects both testis and phallus development in mice (#30)

Andrew Pask 1 , Melanie Stewart 1 , Luke Govers 1
  1. The University of Melbourne, The University Of Melbourne, VICTORIA, Australia

Disorders of sexual development (DSDs) are among the most common birth defects in humans, and their incidence is increasing. In particular, the incidence of the DSD, hypospadias, has risen dramatically in developed countries over the last 50 years. This increase has at least in part been attributed to our exposure to environmental endocrine disruptors (EEDs) especially those that mimic oestrogen. This study examined the effects of the potent oestrogenic endocrine disruptor, diethylstilbestrol (DES) on male urogenital development in mice. Exposed embryos showed a skewed sex ratio and reduced anogenital distance (AGD) in male pups. Hypospadias was present in males at a high frequency and we also observed the first case of epispadias linked to oestrogen exposure. Unexpectedly, no correlation was observed between the AGD and the severity of the hypospadias phenotype, suggesting disrupted androgen signalling did not cause the observed genital tubercle defects. This raises the possibility of DES having direct effects on genital tubercle development. DES exposed testes, examined at embryonic day 14.5, exhibited an increased proportion of cytoplasmic SOX9, suggesting oestrogen exposure affects early Sertoli cell function. Together, our data suggest oestrogenic EEDs affect multiple aspects of urogenital development which may manifest in synergistic effects on phallus development, and especially urethral closure, further support the link between EEDs and the increasing incidence of testicular and phallus DSDs in humans.