Sunday, July 22, 2012

Gender part five: Sex determination in some animals

Note: This program first aired on July 21, 2012.

In many species of animal, what makes a male a male and a female a female is tightly controlled by genetic regulation. This makes sense, as species that reproduce sexually rely on having both sexes represented in the population. In other animals though, sex determination is controlled by environmental factors, usually temperature. And if you have been listening to this show long enough, you should be able to guess by now that there is a third system, that is a blend of these two mechanisms.

To begin, regardless of the system used, all of us vertebrates start out with indifferent or bipotential gonads. These could develop into either ovaries or testes. The first mechanism for this differentiation to occur is called Genotypic Sex Determination (or GSD), in other words, the genes you inherit from your parents determine your functional sex. We talked about this quite a bit when we looked at the phenomenon of male nipples. We are familiar with this system because, barring complications that is how it works for most of us mammals. In fact, the group that includes us, the Eutherian Mammals is the most strictly GSD group of animal out there!

The second system is called Temperature Dependent Sex Determination (or TSD), and is favored by many fish and reptiles. In this system, the development of the gonads from the bipotential state is regulated by environmental temperature, during a specific window of early development, called the thermosensitive period. Species utilizing this method have specific temperature thresholds, above, below, or inbetween which the sex determination switches. The third process is the blend. It turns out that some fish and reptiles have a genetically determined sex, but those sex chromosomes can be overridden by environmental temperature, a phenomena and area of research called epigenetics, or the factors that act on genes, turning them on and off. Its these two mechanisms that I want to talk about today, and we can talk about them together because it turns out that the details are the same in both, whether the fish or reptile has sex chromosomes or not.

The primary influence on the sex determination of any non mammalian vertebrate is the ratio of androgens (male hormones like testosterone) to estrogens. The key factor in temperature dependent sex determination seems to be an enzyme called aromatase. It job is to turn androgens into estrogens, thus affecting the critical androgen/estrogen balance. When aromatase is upregulated, androgens are readily converted to estrogen and the result is female. When the aromatase is down regulated, estrogen is not formed and the result is male. In fish that exhibit some form of TSD, the pattern is well established. Temperatures warmer than a critical threshold (that varies by species), down regulate the genes that produce the aromatase enzyme. Warmer water strongly biases the sex ratio in susceptible fish populations towards males. This has been inadvertently demonstrated in some aquaculture operations; the larval fish are kept in artificially warm environments to increase their growth rate, and have turned out to be almost entirely male as well!

Reptiles show much more diversity with TSD. Warm temperature affect lizards and crocodiles differently than it does turtles. In lizards and crocodiles, warm temperatures yield males, like fish. In turtles the opposite seems to be true, warm temperature biases towards females.  This points to multiple pathways for the upregulation and down regulation of aromatase producing and regulating genes.

As a final note from developmental biology, there is strong evidence that even with the plasticity of sex in these organisms, once the developmental window is closed, gender is permanently established. Changing the temperature for the duration of embryonic development will not change the gender of the organism again.

References: Three really good and readable articles with lots of good background information:

Navarro-Martín L, Viñas J, Ribas L, Díaz N, Gutiérrez A, et al. (2011) DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass. PLoS Genet 7(12): e1002447. doi:10.1371/journal.pgen.1002447

Pieau C. and Dorizzi M. Oestrogens and temperature-dependent sex determination in reptiles: all is in the gonads Journal of Endocrinology June 1 2004 181

Barske, Lindsey and Capel, Blanche Blurring the Edges in Vertebrate Sex Determination Curr Opin Genet Dev. 2008 Dec; 18 (6)