Endocrine Abstracts (2013) 32 P645 | DOI: 10.1530/endoabs.32.P645

Prenatal testosterone programming: ontogeny of changes in testis of fetal and prepubertal male sheep

Pedro Pablo Rojas-García1, Mónica Patricia Recabarren1, Daniel Sandoval1, Albert Carrasco1, Romina Fornes1, Rodolfo Rey2, Teresa Sir-Petermann3 & Sergio E Recabarren1

1University of Concepcion, Chillán, Nuble/Biobio, Chile; 2University of Buenos Aires, Buenos Aires, Argentina; 3University of Chile, Santiago/Region Metropolitana, Chile.

The reprogramming effects of an excess of testosterone during pregnancy in males born to PCOS mothers as well as in animal models for PCOS has been only recently evaluated. We have found in a sheep model of PCOS that prenatal T (PT) excess impact on the testis of adults with increased Sertoli cell (SC) number, decreased sperm count, and reduced germ cell (GC) number. The ontogeny of such disruptions and the mechanisms have not been established. This study addressed the impact of PT excess on testis histology and expression of genes modulating testicular function in fetuses of 120 days of fetal age and in prepubertal sheep of 24 weeks of age. Males were born to mothers administered with either T propionate (T-males) or the vehicle (C-males). At both ages, histological parameters were quantified, and mRNA and protein expression of AMH and transcription factors involved in the AMH signaling as well as proteins related to the BT barrier were analyzed by RT-PCR and WB. Testicular weight was similar in fetal C-and T-males while was lower in prepubertal T-males. SC number was similar between T- and C-males fetuses, on the contrary, the SC number was increased and the number of GC was reduced in prepubertal T-males. mRNA expression of AP2 was similar in both groups and ages, but a higher expression of AMH was observed in T-males. The WB of AMH receptor (MISRII) was lower in T-males at both ages. N-cadherin protein expression was similar in T-and C-males fetuses, but lower in prepubertal T-males. Protein expression of connexin 43 was similar in fetuses, but higher in prepubertal T-males compared to C-males. These findings suggest that the altered environment impairing spermatogenesis of adult male sheep after PT exposure begins at prepubertal ages with an abnormal molecular and cellular environment.

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