Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides

Abstract

FOXO3 has been shown to be a critical transcription factor for folliculogenesis in mammals, while the information on its roles in reproduction of nonmammalian vertebrates remains scarce. In this study, two foxo3 homologs, namely foxo3a and foxo3b, were identified in a teleost, the orange-spotted grouper Epinephelus coioides. foxo3a was mainly expressed in the central nervous system, ovary, and gut whereas foxo3b was expressed ubiquitously in tissues examined. In contrast to the dominant expression of mammalian FOXO3 in germ cells but barely detectable in ovarian follicular cells, immunoreactive Foxo3a and Foxo3b were identified both in the ovarian germ cells and follicular cells. The immunointensities of both Foxo3a and Foxo3b in ovarian follicular cells during vitellogenesis were significantly increased stage-dependently, and co-localized with Cyp19a1a. In the nucleus of ovarian follicular cells, both Foxo3a and Foxo3b immunostaining could be detected at the vitellogenic stages. Transient transfection and EMSA showed that Foxo3a and Foxo3b upregulated cyp19a1a promoter activities in vitro through a conserved Foxo-binding site, with the latter being a more potent activator. However, ChIP analysis showed that only Foxo3b binds to cyp19a1a proximal promoter region containing the conserved Foxo-binding site in the vitellogenic ovary. Taken together, these results suggested that Foxo3a and Foxo3b are involved in the ovarian development possibly through regulating the ovarian germ cells as well as follicular cells, and Foxo3b but not Foxo3a may activate cyp19a1a in the ovarian follicular cells during vitellogenesis in the orange-spotted grouper.

Sex-Dependent RNA Editing and N6-adenosine RNA Methylation Profiling in the Gonads of a Fish, the Olive Flounder (Paralichthys olivaceus)

“…The bmp15, an oocyte-expressed signaling molecule, is required for maintenance of the female sexual fate in zebrafish (Dranow et al, 2016). The foxo3 is a critical transcriptional regulator of fish ovarian development by regulating the ovarian germ cells and follicular cells (Liu et al, 2016). Nr0b1, also called dax1, mainly locates in fish primary oocytes and previtellogenic oocyte cells, and its mutation in zebrafish causes female-to-male sex reversal (Chen et al, 2016).…”

Integrated Analysis of mRNA- and miRNA-Seq in the Ovary of Rare Minnow Gobiocypris rarus in Response to 17α-Methyltestosterone

“…mfap4 is also shown to play an important role in the innate immune system of zebrafish (Zakrzewska et al, 2010;Walton et al, 2015) and catfish (Niu et al, 2011). Foxo3a and Foxo3b in ovarian follicular cells during vitellogenesis were significantly increased stage dependently and co-localized with CYP19a1a (Liu et al, 2016). foxo3b retained most of the functions including upregulating cyp19a1a during vitellogenesis of orange-spotted grouper (Liu et al, 2016).…”

“…Foxo3a and Foxo3b in ovarian follicular cells during vitellogenesis were significantly increased stage dependently and co-localized with CYP19a1a (Liu et al, 2016). foxo3b retained most of the functions including upregulating cyp19a1a during vitellogenesis of orange-spotted grouper (Liu et al, 2016). WB revealed that overexpression of miRNA-96 substantially reduced FOXO3 protein expression (Yin et al, 2020).…”

Identification and Characterization of Sex-Biased miRNAs in the Golden Pompano (Trachinotus blochii)

“…Studies have shown that sf1 plays crucial roles in slider turtle sex differentiation and determination [ 43 ] and is an essential regulator of gonad development in Nile tilapia [ 44 ]. Foxo3 has been shown to be involved in ovarian development in the Gobiocypris rarus [ 45 ], and it upregulates cyp19a1a during vitellogenesis in the orange-spotted grouper [ 46 ]. Gata4 is not only required for gonad differentiation in tilapia but also important to gonad development and maturation [ 47 ].…”