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New light shed on male and female brain differences

University of Otago researchers have discovered a new mechanism which contributes to subtle differences between male and female brains and behaviours.

Neurobiologists Associate Professor Ian McLennan and Dr Kyoko Koishi’s findings are published today in the prestigious US-based scientific journal, the Proceeding of the National Academy of Science (PNAS).

They found that male mice lacking a hormone called Müllerian Inhibiting Substance (MIS) show subtle changes in their brain anatomy, and their behaviour is more akin to female mouse behaviour.

In both appearance and sexual behaviour these mice are typically male, but their nonreproductive behaviours are more feminine. For example, male mice are known to explore a new environment more extensively than female mice. Yet, male mice with no MIS showed significantly less inclination to explore.

Associate Professor McLennan says people tend to think of the obvious differences in sexual anatomy when thinking of “males” and “females”.

“However, sex differences occur throughout the entire body. Outside of the primary reproductive organs, the range of male and female characteristics overlap, creating what we call ‘sex biases’ that actually only exist as a generalisation, at the level of the population, such as men being taller than women. This is not always the case, but is an accepted difference between men and women.

“The sex-biases in the body do not define a person’s sex or sexuality. The brain is one of the organs with the greatest sex biases, giving rise to many subtle differences in the behaviour of the sexes. Empathy, for example, has a female bias, but some of the greatest men are empathetic. Likewise, girls engage in less rough and tumble play than boys, but a boy who shuns rough and tumble play is still a boy.” “While our research is still very new and has only involved mice to date, it indicates that MIS plays a much broader role in shaping the non-reproductive behaviours of males – such as, the male tendency to explore and spatial processing. But further work is needed to determine which human traits are regulated by MIS.” Associate Professor McLennan says the discovery of the mechanisms underlying gender-linked characteristics edges science towards a greater understanding of human diversity.

“The challenge is not just to understand how we develop as women or men, but to also comprehend why the male population encompasses the warrior, the poet, the scientist and wonderful blends of these extremes.” The findings also have implications for research into brain disorders, many of which are more common or more severe in one or other of the sexes.

“Females are more prone to developing anorexia and Alzheimer’s disease, whereas ADHD [Attention Deficit Hyperactivity Disorder], anti-social personality and motor neurone disease have a male bias.” Associate Professor McLennan says the presence of sex-biases in brain disorders suggests that the subtle differences between the brains of males and females alter the course and/or presentation of brain diseases.

“This provides a route to explore the mechanisms that underlie brain disorders and options for the development of new therapies, some of which may be male- or femalespecific.” Scientists have been aware of MIS, which only occurs in men, for about 100 years.

But it was always thought to have a single function in male development – to prevent the formation of a uterus. However, the Otago research indicates that MIS has a wider influence than previous thought.

“The role of MIS does not however diminish the importance of societal influences.

While MIS may determine some male characteristics, the totality of a given man is a result of complex interplay between MIS, other biological factors and the social world in which he lives,” Associate Professor McLennan says.

The research was supported through a $750,000 Marsden Fund grant and an Otago Research Grant.

Postdoctoral fellow Dr Andrew Clarkson (Neurological Foundation), doctoral students Pei-Yu Wang and Floriane Imhoff, undergraduate student Anna Protheroe and technician Nicola Batchelor were key contributors to the research.

Background notes:

Many behavioral traits, while not the exclusive providence of females or males, are more strongly associated with one sex. The Otago researchers’ new work in mice reveals that the cause of these sex-linked behavioral traits goes beyond testosterone, bringing to light a new role for the hormone Müllerian Inhibiting Substance (MIS).

Testosterone imparts the dimorphic nature of the neurons that control sexual function differently in males and females, but testosterone is not present during the most extensive period of foetal brain development.

To determine what else might be contributing to sex-linked behavioral traits, the researchers investigated the potential role of MIS. MIS is responsible for regression of the Müllerian ducts, or uterine precursors, in male fetuses. While its level in males remains high until puberty, its further function is unknown. The researchers found that most neurons in mice have an MIS receptor.

They then then charted the behaviors of male and female mice missing the gene for MIS or its receptor. Male mice missing either of these, while still undoubtedly male, showed a feminisation of some behavioral traits implicating a role for MIS well beyond gestation.

ENDS

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