Exploring different pathways for testosterone mediated maternal effects

PhD ceremony: mw. K.A. Pfannkuche, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Exploring different pathways for testosterone mediated maternal effects

Promotor(s): prof. A.G.G. Groothuis

Faculty: Mathematics and Natural Sciences

The thesis of Kristina Pfannkuche concerns the effects of maternal testosterone and how these are mediated. Two potential pathways are investigated, brain lateralization and the hypothalamic-pituitary-gonadal (HPG) axis.

Pfannkuche showed for the first time that maternal testosterone affects the endogenous testosterone production of young birds and that the expression of androgen receptor mRNA is affected by elevated prenatal testosterone levels. In addition, it has never been shown before, that young chicken show competitive behavior and that this behavior is androgen dependent. Probably as most researchers assume that young precocial birds do not show competitive behavior as they do not rely on parental provisioning.

Previous studies on the effects of androgens on lateralization manipulated testosterone levels in later embryonic stages or used pharmacological dosages. Both does not reflect natural variations of prenatal testosterone levels and the study of Pfannkuche is the first to manipulate maternal testosterone levels within the natural range.

Pfannkuche used a meta-analytic and semi-quantitative approach. Her results supported a consistent sex differences in the direction of lateralization, but not whether sex differences are due to prenatal testosterone.

The domestic chicken proved to be an excellent model for this thesis. In contrast to earlier studies Pfannkuche did not only focus on young chicks, but followed individuals into adulthood, testing the consistency of lateralization and analyzing differences in phenotypic traits. Prenatal testosterone however had no effects on the lateralization of young or adult birds.

Elevated maternal testosterone did not affect lateralization, but Pfannkuche did find effects on competitive behaviour of young chicks and phenotypic traits in adult birds. She found in both age classes a feminizing effect. In the young chicken, male behavior shifted towards females and in adult males, maternal testosterone shifted phenotypic traits towards female like findings. She predicted that maternal testosterone may affect the HPG-axis by suppressing either testosterone production or androgen receptor densities or both and thereby mediate the found effects.

In line with the previously found feminizing effect, elevated maternal testosterone levels lowered the endogenous testosterone production and the AR mRNA expression in the hypothalamus in young chicken. Two hypotheses could explain these findings. Exposure to high prenatal testosterone might induce a postnatal overcompensation or autoregulatory processes are the underlying mechanism.

Next, Pfannkuche analyzed blood samples and brains of chicken embryos shortly before hatching. Her results undermined the autoregulation hypothesis in favor of the overcompensation hypothesis. Although overall male and female embryos did not differ in the expression levels of AR mRNA, within males, testosterone treated individuals showed decreased AR mRNA expression whereas females were not affected.