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The Ouroboros of Human Evolution: Global Decline of Male Fertility and Increase in Cancer

Jekaterina Erenpreisa*

Two global tendencies: The decline in male fertility and increase in cancer are very alarming. Here we present the extended Mini-Review of the recently published article and some literature references analyzing the reciprocal link (ouroboros) of both pathologies. We showed that it was rooted in multicellular evolution and became enhanced by current environmental pollution and endocrine disruption. The findings are based on the phylostratigraphic analysis of the networked functional modules of ~1500 gametogenic genes which have evolved from Unicellulars to Homo sapiens. The evolutionary key to the link for male reproduction and cancer was revealed in the multicellulars of the Cambrian explosion (~500 Mya) when innate immunity/inflammation (including the proto-placental genes) and hormonal sex determination emerged, shared and hubbed by stress-response genes FOS/JUN and cytokine IL1β. The Achilles heel of male sex determination is hidden in its archetypal male-female reversal, triggered by stress and endocrine disruption. This reversal likely redirects tissue proliferation towards the mito-meiotic transition creating the pseudo-parthenogenetic Polyploid Giant Cancer Cells (PGCCs). The latter firstly evolved in unicellulars and early metazoans as part of sporogenesis and embryogenesis. Reciprocally, somatic sex reversal causes suppression of spermatogenesis, strengthened in late mammalian evolution by Cancer Testis Associated Genes (CTA/MAGEA group) in collaboration with testosterone-responsive androgen receptors. In addition, the placental syncytin glycoproteins, created by mammalian domestication of endogenous retroviruses and employed in cell fusion and immunity suppression, can cause fusion of cancer and somatic cells for the organ-targeted metastases. Alternatively, both germinative and the cytotrophoblast components can differentiate within a single multinucleated PGCC.