The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer

Jekaterina Erenpreisa (Coresponding Author), Ninel Miriam Vainshelbaum, Marija Lazovska, Roberts Karklins, Kristine Salmina, Pawel Zayakin, Felikss Rumnieks, Inna Inashkina, Dace Pjanova, Juris Erenpreiss

Research output: Contribution to journalReview articlepeer-review


The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.

Original languageEnglish
Article number11660
JournalInternational Journal of Molecular Sciences
Issue number14
Publication statusPublished - Jul 2023


  • cancer-testis antigens
  • endocrine disruption
  • endogenous retroviruses
  • environmental pollution
  • genome fragility
  • innate immunity placentation
  • male infertility
  • parthenogenetic
  • PGCCs
  • phylostratigraphic analysis
  • polyploid giant cancer cells
  • sex determination

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


Dive into the research topics of 'The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer'. Together they form a unique fingerprint.

Cite this