Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

• DOI: 10.1073/pnas.1320735111
• Publication Date: 2014-04-22T02:50:54Z
• Authors: Karen R. Kilcoyne; Lee B. Smith; Nina Atanassova; Sheila Macpherson; Chris McKinnell; Sander van den Dr...; Matthew S. Jobling; Thomas J. G. Cham...; Karel De Gendt; Guido Verhoeven; Laura O’Hara; Sophie Platts; Luiz Renato de Fr...; Nathália L. M. Lara; Richard A. Anderson; Richard M. Sharpe
• Keywords: Male; 0301 basic medicine; Mice, Transgenic; Adult Leydig stem/progenitor cells; In Vitro Techniques; Fetal Development; GATA4; Mice; 03 medical and health sciences; Pregnancy; Animals; Humans; Cell Lineage; Mice, Knockout; Fetal Stem Cells; Ethane dimethane sulfonate; Leydig Cells; Callithrix; Luteinizing Hormone; Dibutyl Phthalate; Mice, Inbred C57BL; Adult Stem Cells; Models, Animal; Androgens; compensated Leydig cell failure; Female

Significance Men are defined by androgens (testosterone), which drive fetal masculinization (male development) and puberty and maintain masculinity in adulthood, including sex drive, erectile function, and fertility. Moreover, Western cardiometabolic diseases are all associated with lowered testosterone levels in men. Therefore, influences on testosterone levels in adulthood have pervasive importance for masculinity and health. Our study shows, for the first time, to our knowledge, that testosterone levels during fetal masculinization can (re)program adult testosterone levels through effects on stem cells, which develop into adult Leydig cells (the source of testosterone) after puberty. These stem cells are present in fetal testes of humans and animals, and using the latter, we show how these cells are reprogrammed to affect adult testosterone levels.