Differential role of r-met-hu G-CSF on male reproductive function and development in prepubertal domestic mammals

Autoři: Pedro M. Aponte aff001;  Miguel A. Gutierrez-Reinoso aff004;  Edison G. Sanchez-Cepeda aff005;  Manuel Garcia-Herreros aff006
Působiště autorů: Colegio de Ciencias Biológicas y Ambientales, Universidad San Francisco de Quito (USFQ), Campus Cumbayá, Quito, Ecuador aff001;  Colegio de Ciencias de la Salud, Escuela de Medicina Veterinaria, Universidad San Francisco de Quito (USFQ), Campus Cumbayá, Quito, Ecuador aff002;  Instituto de Investigaciones en Biomedicina “One-health”, Universidad San Francisco de Quito (USFQ), Campus Cumbayá, Quito, Ecuador aff003;  Facultad de Ciencias Agropecuarias y Recursos Naturales, Carrera de Medicina Veterinaria, Universidad Técnica de Cotopaxi (UTC), Latacunga, Ecuador aff004;  AGROCALIDAD, Ambato, Ecuador aff005;  National Secretariat Higher Education, Science, Technology and Innovation (SENESCYT), Quito, Ecuador aff006;  Instituto Nacional de Investigação Agrária e Veterinária, I. P. (INIAV, I.P.), Polo de Santarém, Santarém, Portugal aff007
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222871


The understanding of mammalian spermatogenesis niche factors active during sexual development may be leveraged to impact reproduction in farm animals. The aim of this study was to evaluate the effects of r-met-hu/G-CSF (filgrastim) on prepubertal sexual development of guinea pigs (Cavia porcellus) and ram lambs (Ovis aries). Individuals of both species were administered r-met-hu/G-CSF daily for 4 days. During and after administration protocols, testicular function and development were assessed through hematological responses, hormonal profiles (gonadotropins, testosterone and cortisol) testicular morphometry and germ cell kinetics. As expected, r-met-hu/G-CSF acutely mobilized white-lineage blood cells in both species. LH was increased by r-met-hu/G-CSF in guinea pigs (P<0.01) but T remained unchanged. In ram lambs gonadotropins and T increased in dose-response fashion (P<0.01) while cortisol values were stable and similar in treated and control animals (P>0.05). In guinea pigs there were no differences in testicular weights and volumes 2-mo after r-met-hu/G-CSF application (P>0.05). However, ram lambs showed a dose-response effect regarding testis weight (P<0.05). 66.66% of ram lambs had initial testes not yet in meiosis or starting the first spermatogenic wave. After 60-days only 25% of control animals were pubertal while all treated animals (1140-μg) had reached puberty. We propose an integrated hypothesis that G-CSF can stimulate spermatogenesis through two possible ways. 1) r-met-hu/G-CSF may go through the brain blood barrier and once there it can stimulate GnRH-neurons to release GnRH with the subsequent release of gonadotrophins. 2) a local testicular effect through stimulation of steroidogenesis that enhances spermiogenesis via testosterone production and a direct stimulation over spermatogonial stem cells self-renewal. In conclusion, this study shows that r-met-hu/G-CSF differentially affects prepubertal sexual development in hystricomorpha and ovine species, a relevant fact to consider when designing methods to hasten sexual developmental in mammalian species.

Klíčová slova:

Germ cells – Guinea pigs – Sperm – Spermatogenesis – Testosterone – Seminiferous tubules – Spermatids – Sexual differentiation


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