Estrogen treatment up-regulates female genes but does not suppress all early testicular markers during rainbow trout male-to-female gonadal transdifferentiation.
In non-mammalian vertebrates, estrogens are key players in ovarian differentiation, but the mechanisms by which they act remain poorly understood. The present study on rainbow trout was designed to investigate whether estrogens trigger the female pathway by activating a group of early female genes (i.e. cyp19a1, foxl2a, foxl2b, fst, bmp4, and fshb) and by repressing early testicular markers (i.e. dmrt1, nr0b1, sox9a1 and sox9a2). Feminization was induced in genetically all-male populations using 17alpha-ethynylestradiol (EE2, 20 mg/kg of food during 2 months). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR and 45 expression profiles displayed a significant differential expression between control populations (males and females) and EE2-treated populations. These expression profiles were grouped in five temporally correlated expression clusters. The estrogen treatment induced most of the early ovarian differentiation genes (foxl2a, foxl2b, fst, bmp4, and fshb) and in particular foxl2a, which was strongly and quickly up-regulated. Simultaneously, Leydig cell genes, involved in androgen synthesis, as well as some Sertoli cell markers (amh, sox9a2) were strongly repressed. However, in contrast to our initial hypothesis, some genes considered as essential for mammalian and fish testis differentiation were not suppressed during the early process of estrogen-induced feminization (dmrt1, nr0b1, sox9a1 and pax2a) and some were even strongly up-regulated (nr0b1, sox9a1and pax2a). In conclusion, estrogens trigger male-to-female transdifferentiation by up-regulating most ovarian specific genes and this up-regulation appears to be crucial for an effective feminization, but estrogens do not concomitantly down-regulate all the testicular differentiation markers.
Vizziano-Cantonnet
Denise
D
Facultad de Ciencias, Oceanología, Iguá 4225, Montevideo 11400, Uruguay INRA, UR1037, IFR140, SCRIBE, F-35000 Rennes, France.
Baron
Daniel
D
Mahè
Sophie
S
Cauty
Chantal
C
Fostier
Alexis
A
Guiguen
Yann
Y
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054338:Cell Transdifferentiation; D016000:Cluster Analysis; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006066:Gonads / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D005810:Multigene Family; D017686:Oncorhynchus mykiss / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology
D015415:Biomarkers; D004967:Estrogens