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Reproduction Abstracts (2014) 1 P175 | DOI: 10.1530/repabs.1.P175


Early life programming of adult Leydig cell function

Karen R Kilcoyne1, Lee Smith1, Matthew Jobling1, Chris McKinnell1, Sheila MacPherson1, Sander van den Driesche1, Karel De Gendt2, Guido Verhoeven3, Richard Anderson1 & Richard Sharpe1


1University of Edinburgh, Edinburgh, UK; 2Catholic University of Leuven, Leuven, Belgium; 3Legendo, Leuven, Belgium.

Introduction: Adult male testosterone levels are influenced by fetal events, but how is unknown, as adult Leydig cells (ALC) do not differentiate until puberty. We hypothesised that adult Leydig stem cells are present in the fetal testis, and are susceptible to programming by fetal androgen exposure. We have shown that ALC derive from interstitial cells that express chicken ovalbumin upstream promoter transcription-factor II, essential postnatally for ALC development, and androgen receptor (AR). These cells are androgen regulated and present in the fetal testis across species. As deficient fetal androgen action is implicated in the origin of male reproductive disorders, we investigated a potential mechanism to explain how fetal programming of adult Leydig stem cells occurs.

Materials and methods: AR knockout mice were generated by Cre/LoxP technology. Pregnant female rats were treated daily (e13.5–e21.5) with 500 mg/kg per day DBP in 1 ml/kg corn oil. Testes from DBP-exposed rats were evaluated in adulthood using RT-PCR, triple IHC and ChIP. Testosterone and LH were measured in blood plasma.

Results and discussion: Reduction in fetal androgen action via AR knockout (mice) or dibutyl phthalate (DBP)-induced reduction in intratesticular testosterone (rats), reduced adult Leydig stem cell number by ~40% at birth through to adulthood, and induced compensated ALC failure (low/normal testosterone and elevated LH). Reduced Star transcription in DBP-exposed adult rats may occur as a result of increased trimethylation of Lys27 at histone 3 (H3K27me3), in the proximal promoter of Star. These findings suggest that fetal androgen exposure can fundamentally reprogramme adult hormone production and thus overall male health.

Volume 1

World Congress of Reproductive Biology 2014

Edinburgh, UK
02 Sep 2014 - 04 Sep 2014

World Congress of Reproductive Biology 

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