Reversed sex roles: In seahorses, it is the males who carry offspring to term. The females lay their eggs into a special brood pouch on the bellies of the males where they are fertilized by the male’s sperm. In the brood pouches, embryos are provided with nutrients and oxygen from the males’ bodies until the males give live birth to small seahorses (viviparity). But how does this work? A German-Chinese research team led by evolutionary biologist Axel Meyer from the University of Konstanz and working in collaboration with Liu Yali and Lin Qiang from the South China Sea Institute for Oceanography in Guangzhou studied the genetic and cellular mechanisms behind this sex-role reversal. They uncovered that unusual hormonal processes and unique immunotolerance strategies allowed this to evolve.

The brood pouch – an evolutionary innovation
From an evolutionary perspective, the brood pouch is an extraordinary innovation – along with “male pregnancy”. In seahorses, the brood pouch fulfils the tasks of the uterus and placenta. During pregnancy, the male’s pouch tissue changes and builds a structure similar to the mammalian female placenta.

It is surprising how this works, and the researchers studied the process with comparative genomic methods using RNA analyses on a cellular basis. They compared the cells and cellular signals in the placentas of mammals with those in the brood pouches of male seahorses. In all other cases of live birth, female hormones play a key role in the development of pregnancy structures and embryos. Yet, as Axel Meyer and his team have now shown, male pregnancy in seahorses interestingly takes place without these typical female hormones.

“Our research confirms that androgens – that is: male sexual hormones – play a central role in the development of embryos in the brood pouches, instead of female hormones”, Axel Meyer explains. “Androgens induce the thickening and vascularization of the abdominal skin layer to produce a structure similar to a mammalian placenta. This is an interesting difference to the development in the female uterus of mammals, including humans, that is typically driven by female hormones”.

Studying the immune system also yielded surprising results. For live birth, it is critical that the immune system of the mother – or, in this case, the male seahorse – does not identify embryos as foreign bodies and reject them immunologically. Typically, the gene foxp3 fulfils this task as a key gene in the immune system of many viviparous species. Surprisingly, however, precisely this gene is missing in the case of male seahorses. Yet, no autoimmune reaction takes place in which the male’s body rejects the embryonic seahorses. Axel Meyer suspects that seahorses employ an unusual immune tolerance strategy in which male hormones could again play a decisive role: “Androgens often have an immunosuppressant effect, which means they suppress the immune response. This could contribute to this unique immunotolerance.”

The genetic and cellular characteristics of brood pouches provide fascinating insight into the evolutionary development from species that lay eggs to species with live birth. “The different evolutionary stages within the family Syngnathidae make seahorses an exceptional model for studying evolution from oviparous (egg-laying) ancestors to viviparous reproduction.”

Presumably, an early step was the development of “sticky eggs” that attached to the males’ bodies, which, at the time, did not yet have brood pouches. The next evolutionary step was the development of the males’ brood pouches to hold and protect the eggs and supply them with nutrients.

“Thanks to our research, we now have a better understanding of the genetic, molecular and cellular mechanisms behind this remarkable evolutionary experiment – pregnancy evolved repeatedly in female mammals and male seahorses, but by different genetic and hormonal pathways”, Axel Meyer concludes.