March 3, 2020

How a marine animal makes unlimited eggs and sperm

At a Glance

  • Activation of one particular gene in the adult stem cells of a marine animal called Hydractinia symbiolongicarpus leads to unlimited production of eggs and sperm.
  • The findings could provide insight into the development of the human reproductive system and the causes of reproductive conditions and diseases.
Female Sexual Polyp of Hydractinia A Female Sexual Polyp of Hydractinia symbiolongicarpus. Oocytes (female germ cells) are shown in yellow, cell nuclei in turquoise.Timothy DuBuc, Ph.D. Swarthmore College

Most mammals—including people—generate a specific number of germ cells (the precursors to eggs and sperm) only once in their life. During human embryonic development, this small pool of germ cells is set aside, and all sperm or eggs that a person produces over his or her lifetime are the descendants of those original germ cells. Loss of these germ cells for any reason results in sterility.

In contrast, a close relative of jellyfish and corals called Hydractinia can produce germ cells nonstop throughout its life. That allows it to make eggs and sperm across its lifespan. These animals live in colonies and take on separate tasks. The colony forms specialized tubular-shaped outgrowths called polyps. For example, they form feeding polyps, in which digestion takes place. Sexual polyps, which produce eggs and sperm, are functionally similar to gonads in species like humans.

Although Hydractinia look and function very different from humans, their genome contains a large number of genes that are similar to human disease genes. To investigate this distant animal relative’s noteworthy reproductive capacity, a group of international researchers that include Dr. Andy Baxevanis’s lab at NIH’s National Human Genome Research Institute (NHGRI) compared gene expression between the animal’s feeding and sexual polyps. The study appeared on February 14, 2020, in Science.

Male Sexual Polyp of Hydractinia A male Sexual Polyp of Hydractinia symbiolongicarpus. Spermatogonia (male germ cells) are shown in yellow, cell nuclei in turquoise. Timothy DuBuc, Ph.D. Swarthmore College

The researchers found that a gene called Tfap2 was more active in sexual polyps than in the feeding polyps in both males and females. Using the CRISPR-Cas9 gene-editing technique, they removed Tfap2 from Hydractinia and measured its effects on germ cell production. Hydractinia lacking this gene stopped forming germ cells.

The researchers investigated which cell types Tfap2 affects. Their analysis revealed that Tfap2 could not turn somatic cells (body cells other than reproductive cells) into germ cells. Tfap2 only caused adult stem cells in Hydractinia to turn into germ cells. Although some embryonic stem cells showed early signs of turning into germ cells, these eventually disappeared. The authors suggest that the young animal’s tissue environment can’t support germ cell growth; such cells aren’t normally made until a few months into adulthood.

The Tfap2 gene also regulates germ cell production in humans, in addition to other processes. Despite the vast evolutionary distance between Hydractinia and humans, the findings suggest that both share a key gene that changes stem cells into germ cells.

“By sequencing and studying the genomes of simpler organisms that are easier to manipulate in the lab, we have been able to tease out important insights regarding the biology underlying germ cell fate determination—knowledge that may ultimately help us better understand the processes underlying reproductive disorders in humans,” Baxevanis says.

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References: Transcription factor AP2 controls cnidarian germ cell induction. DuBuc TQ, Schnitzler CE, Chrysostomou E, McMahon ET, Febrimarsa, Gahan JM, Buggie T, Gornik SG, Hanley S, Barreira SN, Gonzalez P, Baxevanis AD, Frank U. Science. 2020 Feb 14;367(6479):757-762. doi: 10.1126/science.aay6782. PMID: 32054756.

Funding: NIH’s National Human Genome Research Institute (NHGRI); Wellcome Trust; Science Foundation Ireland; Health Research Board; European Molecular Biology Organization; European Commission; National University of Ireland Galway.