Jeanette Axelsson

Sex-dependent gene expression in early brain development of chicken embryos

BackgroundDifferentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.ResultsUsing cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head) that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females) were common among the differentially expressed genes, several of which (WPKCI-8, HINT, MHM non-coding RNA) have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7, CCNH and BTF2-P44) encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation.ConclusionIn conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.

Effects of estrogens on sex differentiation in Japanese quail and chicken.

Estrogen production by the female avian embryo induces development of a female phenotype of the reproductive organs whereas the low estrogen concentration in the male embryo results in a male phenotype. Treatment of female embryos with exogenous estrogens disrupts Müllerian duct development resulting in malformations and impaired oviductal function. Exposure of male embryos to estrogens results in ovotestis formation and persisting Müllerian ducts in the embryos and testicular malformations, reduced semen production and partially developed oviducts in the adult bird. Furthermore, studies in Japanese quail show that the male copulatory behavior is impaired by embryonic estrogen treatment. Results from our experiments with selective agonists for ERalpha and ERbeta suggest that the effects of estrogens on the reproductive organs are mediated via activation of ERalpha. Abundant expression of ERalpha mRNA was shown in gonads and Müllerian ducts of early Japanese quail embryos. Both ERalpha and ERbeta transcripts were detected by real-time PCR in early embryo brains of Japanese quail indicating that both receptors may be involved in sex differentiation of the brain. However, in 9-day-old quail embryo brains in situ hybridization showed expression of ERbeta mRNA, but not of ERalpha mRNA, in the medial preoptic nucleus (POM) and the bed nucleus of the stria terminalis (BSTm), areas implicated in copulatory behavior of adult male quail. Furthermore, embryonic treatment with the selective ERalpha agonist propyl pyrazol triol (PPT) had no effect on the male copulatory behavior. These results suggest that ERbeta may be important for the effects of estrogens on brain differentiation.

Effects of Endocrine Modulators on Sex Differentiation in Birds

This mini-review focuses on sexual differentiation of the reproductive organs and the brain in birds and the effects of endocrine modulators on these processes. Sex determination in birds is genetically controlled, but the genetic events implicated are largely unknown. Female birds have one Z and one W sex chromosome, while males have two Z sex chromosomes. It is not clear whether it is the presence of the W chromosome in females, the double dose of the Z chromosome in males vis-à-vis females, or both of these characteristics that are crucial for the determination of sex in birds. Oestradiol directs sexual differentiation in birds during critical periods of development. Consequently, exogenous compounds that interfere with the endogenous oestrogen balance can disrupt sexual differentiation of the reproductive organs and the brain. Therefore, sexual differentiation in birds provides a good model for studying the effects of endocrine modulators at various biological levels from gene expression to behaviour. Some compounds known to be present in the environment can alter endocrine function and have adverse effects when administered during development, resulting in alterations in gonads, accessory sexual organs, and behaviour. Data reviewed in this paper are mostly from laboratory studies on endocrine modulators with oestrogenic activity, whereas evidence for adverse effects of pollutants on sexual differentiation in avian wildlife is scarce.

Developmental toxicity in Japanese quail exposed to hydroxylated metabolites pf PCBs in ovo.

Developmental toxicity in Japanese quail exposed to hydroxylated metabolites pf PCBs in ovo.