Developmental Biology Ecology

Sex Change 101: it Starts in the Brain

Dodd, L.D., Nowak, E., Lange, D., Parker, C.G., DeAngelis, R., Gonzalez, J.A. and Rhodes, J.S., 2019. Active feminization of the preoptic area occurs independently of the gonads in Amphiprion ocellaris. Hormones and behavior, 112, pp.65-76.

Carpet Anemone with True Percula Clownfish and Blue Hepatus Tang by Brian Daniel Eisenberg. Licensed under CC BY-NC 2.0

The preoptic area (POA) is the portion of the hypothalamus responsible for regulating reproductive physiology and behaviour. During sexual development, the POA is completely restructured. Mammalian gonads are also completely restructured during development including maturation of eggs and sperm, and release of sexual hormones. Rat masculinization occurs following spikes in male sex hormones (known as androgens). Because estrogens, female reproductive hormones, are not secreted during development in the same way, mammalian feminization was long believed to be a passive process. This idea is now being challenged, but the signal to begin development is yet unknown. The concept of mammalian feminization is a typical chicken-or-the-egg type problem. Does the brain tell the gonad to begin sexual development? Or does the gonad tell the brain? Here, Dodd et al., use sequential hermaphrodite Amphiprion ocellaris, the common clownfish (a.k.a Nemo) to explore this concept.


Sequential hermaphroditism?

Clownfish form mating pairs with the female being the largest and most dominant in the group. When a new group is formed, dominance is established amongst the mature males. The dominant male will then undergo feminization, transforming into a female. If an existing group loses its female, then the mature male will transform into the dominant female, and one of the undifferentiated (immature) fish will mature into a male. Because clownfish development is easily manipulated (remove the female), they make excellent models for developmental biology.

Conceptual diagram of clownfish sequential hermaphroditism created by B. Biggar from images by Unknown Author, licensed under CC BY-NC-ND.


The Study

In a laboratory, thirty-four mature males were removed from their female partners and randomly paired up. Pairs were observed for the first hour after pairing, where individuals approached each other and began the battle for dominance. They were then observed every day until dominance had been established (within a few days). Once there was a clear hierarchical structure, pairs were sampled at 3 weeks, 6 months, 1 year, and 3 years for hormones in the blood; brain and gonad histology  were also examined at these times.


The Sex Change

Over the three years, the dominant fish grew, while the subordinate one did not, leading to a visible differentiation in morphology. The brain of the dominant fish began feminizing with an increase in the number of POA cells. Gonadal tissue degenerated in both members of the pair, possibly to divert energetic costs while reproduction was not necessary. In clownfish, mature males have the reproductive organs of both sexes (ambisexual). Testicular tissue makes up ~70% of the gonad, while non-vitellogenic (non-viable) eggs are ~30%. Throughout feminization, testicular tissue continues to degenerate until none is left. The final step to a successful sex change is fill the gonad with 100% vitellogenic-oocytes (viable eggs).  Despite plenty of evidence of sex change occurring, only three of the seventeen pairs completed gonadal sex change within the time frame of this study.

A, B. Length and weight of studied fish. Bars go between each pair. Symbols show the time since start of study. C, D. Length and weight vs sampling time. Horizontal bars represent the mean, vertical bars the confidence interval.


So… Which Comes First?

In this study, feminization of the POA occurred first. Male gonad tissue began degenerating early on but did not appear to be directly related to the sex change. Female gonad tissue did not differentiate until much later, and sexual hormones did not change until even after this! In other words, clownfish brains undergo sex change before the gonad; sometimes even years before!

It appears that sex change begins in the brain, and sex organs can remain ambisexual until some yet-unknown signal conveys the message to complete the process.


Back to the mammals

If these results hold true for mammals, we might expect female development to begin in the brain, possibly years before changes in sex organs. These results may not directly apply to mammals, but they give the first evidence of active feminization, an interesting story, and a good place to start with future work.

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