Abstract
What is Wrong with the Human Reproductive System? Human reproduction is highly inferior by mammalian standards. This is manifest as: (i) poor semen quality; (ii) a lower probability of conception; (iii) an increased risk of aneuploidy embryos (e.g. Down syndrome); (iv) a high risk of embryonic loss (early miscarriage); and (v) the recent rise of germ-cell testicular cancer, which occurs in few non-human mammalian species. Review and synthesis of the evidence from several distinct research areas reveals a shared pathogenesis underlying at least some cases of all of them. This involves an intergenerational process, starting with DNA damage to round spermatids. DNA repair in the oocyte is faulty, leading to abnormal chromosome structure in the surviving embryos. This is amplified during meiosis due to delayed synapsis, leading to cellular disorganization. This mechanism also explains the association of aneuploidy with maternal age: structural mismatch between maternal and paternal chromosomes reduces the number of crossovers, making segregation errors more likely.
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