Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development

Abstract

The development of any organ system requires a complex interplay of cellular signals to initiate the differentiation and development of the heterogeneous cell and tissue types required to carry out the organs' functions. In this way, an extracellular stimulus is transmitted to an intracellular target through an array of interacting protein intermediaries, ultimately enabling the target cell to elicit a response. Surprisingly, only a small number of signaling pathways are implicated throughout embryogenesis and are used over and over again. Gonadogenesis is a unique process in that 2 morphologically distinct organs, the testes and ovaries, arise from a common precursor, the bipotential genital ridge. Accordingly, most of the signaling pathways observed throughout embryogenesis also have been shown to be important for mammalian sex determination and gonad development. Here, we review the mechanisms of signal transduction within these pathways and the importance of these pathways throughout mammalian gonad development, mainly concentrating on data obtained in mouse but including other species where appropriate.

Identification of conserved genes triggering puberty in European sea bass males (Dicentrarchus labrax) by microarray expression profiling

“…All these results are supported by the analysis of affected biological pathways (Table 2) that showed higher expression of genes involved in cellular processes, particularly those involved in cell cycle, meiosis and DNA replication and repair. In addition, several signalling pathways involved in testicular development such as Wnt, MAPK, hedgehog and TGF beta signalling pathways [68] were altered during early puberty in European sea bass. Altogether, the upregulation of the above mentioned genes is indicative of an active period of mitosis, reflect the need for a tight control of the correct division of the cells, and constitutes an indicator for the progression of meiosis typical of this stage.…”

“…Likewise, a downregulation of amh during the reproductive cycle has been found in the testicular transcriptome of rainbow trout [12] and in precocious Atlantic salmon [74], further demonstrating that the inhibitory effect of Amh of the onset of puberty can be extended to all fish species so far studied. In addition, the study of the biological pathways affected during the onset of puberty, also show the importance of amh in several signalling pathways including those of TGF beta, hippo and cAMP [68]. Few studies are available for sgII in fish, apart from those in goldfish [75–77].…”

XY (<b><i>SRY</i></b>-positive) Ovarian Disorder of Sex Development in Cattle

“…Indeed, the development of a male or female phenotype is governed by a complex network of genetic, epigenetic, and hormonal components [Windley and Wilhelm, 2015]. The first step of this delicate biological process, named sexual determination, is the formation of gonads in the developing embryo and requires the involvement of several genetic factors.…”

Stress and sex: does cortisol mediate sex change in fish?

“…Following activation of one sex-specific network in early development, sexual fate must be actively maintained through ongoing suppression of the opposing network throughout adulthood (Matson et al 2011, Windley & Wilhelm 2015. Disruption of this process likely causes disorders of sex development (DSD) (Todd et al 2016) involving pathologies causing ambiguous genitalia that affect 1 in 4500 live births (Sax 2002).…”