Hormone-Independent Pathways of Sexual Differentiation

Abstract

New observations over the last 25 years of hormone-independent sexual dimorphisms have gradually and unequivocally overturned the dogma, arising from Jost's elegant experiments in the mid-1900s, that all somatic sex dimorphisms in vertebrates arise from the action of gonadal hormones. Although we know that Sry, a Y-linked gene, is the primary gonadal sex determinant in mammals, more recent analysis in marsupials, mice, and finches has highlighted numerous sexual dimorphisms that are evident well before the differentiation of the testis and which cannot be explained by a sexually dimorphic hormonal environment. In marsupials, scrotal bulges and mammary primordia are visible before the testis has differentiated due to the expression of a gene(s) on the X chromosome. ZZ and ZW gynandromorph finches have brains that develop in a sexually dimorphic way dependent on their sex chromosome content. In genetically manipulated mice, it is the X chromosomes, not the gonads, that determine many characters including rate of early development, adiposity, and neural circuits. Even spotted hyenas have sexual dimorphisms that cannot be simply explained by hormonal exposure. This review discusses the recent findings that confirm that there are hormone-independent sexual dimorphisms well before the gonads begin to produce their hormones.

Sex Reversal and Performance in Fitness-Related Traits During Early Life in Agile Frogs

“…It would be very interesting to perform similar studies with species where either the male or the female parent takes the risky job of providing care to the offspring, as the developmental determinants of sex roles and therefore the effects of sex reversal may vary greatly between traditional and sex-role reversed systems. Amphibians and fish offer excellent model systems for such studies given their great diversity in mating and parental-care systems (Mank et al, 2005;Vági et al, 2019), but notably, sex reversal can also be experimentally induced in birds and mammals to study the development of sex roles (Adkins-Regan and Wade, 2001;Renfree et al, 2014).…”

WOMEN IN REPRODUCTIVE SCIENCE: Reproduction down under

“…While it is yet to be published, the new genome does include over 150 transcriptomes of various reproductive tissues, including an amazing set of transcriptome data completed for us by Prof. Asao Fujiyama and his colleagues at the National Institute of Informatics and the National Institute of Genetics in Japan of the developing phallus after we treated the young with androgens, oestrogens and after castration. These data have shown us just how sensitive the genes of the developing phallus are to exogenous androgens and oestrogens, highlighting their steroid hormone sensitivity (Chew et al 2014, Chen et al 2018a. Furthermore, there are hundreds of long non-coding genes (lncRNAS) that are also up-or down-regulated by the steroid treatments, apparently in concert with their coding genes (Chen et al 2019).…”

“…This novel finding has been amply confirmed and has directed research from multiple laboratories to an entirely new and expanding field of investigation. Direct X and Y chromosome effect, (and Z/W effects in birds), have now been demonstrated in eutherian mammals, particularly in mice, and almost certainly in humans (Arnold 1997, Burgoyne et al 2001, Arnold & Burgoyne 2004, Renfree et al 2014.…”

Sex Reversal in Non-Human Placental Mammals

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