Morphological and functional maturation of Leydig cells: from rodent models to primates.
BACKGROUND
Leydig cells (LC) are the sites of testicular androgen production. Development of LC occurs in the testes of most mammalian species as two distinct growth phases, i.e. as fetal and pubertal/adult populations. In primates there are indications of a third neonatal growth phase. LC androgen production begins in embryonic life and is crucial for the intrauterine masculinization of the male fetal genital tract and brain, and continues until birth after which it rapidly declines. A short post-natal phase of LC activity in primates (including human) termed 'mini-puberty' precedes the period of juvenile quiescence. The adult population of LC evolves, depending on species, in mid- to late-prepuberty upon reawakening of the hypothalamic-pituitary-testicular axis, and these cells are responsible for testicular androgen production in adult life, which continues with a slight gradual decline until senescence. This review is an updated comparative analysis of the functional and morphological maturation of LC in model species with special reference to rodents and primates.


METHODS
Pubmed, Scopus, Web of Science and Google Scholar databases were searched between December 2012 and October 2014. Studies published in languages other than English or German were excluded, as were data in abstract form only. Studies available on primates were primarily examined and compared with available data from specific animal models with emphasis on rodents.


RESULTS
Expression of different marker genes in rodents provides evidence that at least two distinct progenitor lineages give rise to the fetal LC (FLC) population, one arising from the coelomic epithelium and the other from specialized vascular-associated cells along the gonad-mesonephros border. There is general agreement that the formation and functioning of the FLC population in rodents is gonadotrophin-responsive but not gonadotrophin-dependent. In contrast, although there is in primates some controversy on the role of gonadotrophins in the formation of the FLC population, there is consensus about the essential role of gonadotrophins in testosterone production. Like the FLC population, adult Leydig cells (ALC) in rodents arise from stem cells, which have their origin in the fetal testis. In contrast, in primates the ALC population is thought to originate from FLC, which undergo several cycles of regression and redifferentiation before giving rise to the mature ALC population, as well as from differentiation of stem cells/precursor cells. Despite this difference in origin, both in primates and rodents the formation of the mature and functionally active ALC population is critically dependent on the pituitary gonadotrophin, LH. From studies on rodents considerable knowledge has emerged on factors that are involved besides LH in the regulation of this developmental process. Whether the same factors also play a role in the development of the mature primate LC population awaits further investigation.


CONCLUSIONS
Distinct populations of LC develop along the life span of males, including fetal, neonatal (primates) and ALC. Despite differences in the LC lineages of rodents and primates, the end product is a mature population of LC with the main function to provide androgens necessary for the maintenance of spermatogenesis and extra-gonadal androgen actions.
Human and Animal Physiology, Wageningen University, De Elst 1, 6709 WD, Wageningen, The Netherlands katja.teerds@wur.nl.
Katja J
KJ
Teerds
Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0NN London, UK Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Ilpo T
IT
Huhtaniemi
D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D053686:Fetal Stem Cells / Q000166:cytology; D006801:Humans; D007985:Leydig Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D019899:Paracrine Communication / Q000502:physiology; D011323:Primates; D051381:Rats; D012741:Sexual Maturation / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000196:embryology*; D013739:Testosterone / Q000096:biosynthesis
D000728:Androgens; D013739:Testosterone
Leydig cells; animal models; development regulating factors; developmental stage and functionality