Phenotype characteristics of transgenic male mice expressing human aromatase under ubiquitin C promoter

Abstract

To study the significance of the increased ratio of the estrogen/androgen concentration for the male reproductive functions, we have generated transgenic mice expressing human P450 aromatase under a promoter providing ubiquitous and permanent transgene expression (AROM+ mice). AROM+ male mice are characterized by elevated serum estradiol and prolactin (Prl) concentrations, combined with markedly reduced testosterone levels. The mice are present with a multitude of structural and functional alterations in the reproductive organs such as cryptorchidism, Leydig cell hyperplasia, disrupted spermatogenesis and infertility. Furthermore, the mice develop infravesical obstruction associated with the rhabdosphincter atrophy and rudimentary accessory sex glands. Interestingly, the mammary gland in AROM+ males undergo a ductal and alveolar development morphologically resembling terminally differentiated female mammary glands, and express several signaling proteins typical for female mammary glands. Some of the abnormalities seen in AROM+ mice are similar to those described in both mice and humans exposed to diethylstilbestrol (DES) in utero. The importance of the AROM+ model may lie in its predictability, i.e. the model suggests which abnormalities of the human reproductive functions may be associated with the increased ratio of estrogen/androgen concentrations in early life and at adult age as well.