Asian Journal of Biochemistry, Genetics and Molecular Biology

The reproductive organs are conventionally treated as the effectors of a hierarchical endocrine axis, yet the evidence accumulated over the past three decades indicates that their structure and functional capacity are substantially specified by events occurring in the developing brain. This review examines critically how embryonic assembly and postnatal maturation of hypothalamic circuitry shape gonadal and accessory reproductive organ function across the life course, with emphasis on mammalian models and human clinical evidence. Four bodies of literature are appraised and integrated: the extracerebral origin and migration of gonadotrophin-releasing hormone neurones and the reproductive phenotypes that follow when this process fails; the hormonal and genetic organisation of hypothalamic circuits during perinatal life; the transient postnatal activation of the hypothalamic-pituitary-gonadal axis, commonly termed minipuberty, and its role in establishing gonadal cell populations; and non-gonadotrophic neural routes, including autonomic innervation and photoperiodic pathways, that act on reproductive tissues without passing through pituitary gonadotrophins. Evidence linking disrupted neurodevelopment to later reproductive impairment is strongest where a defined molecular lesion, an identifiable developmental window and a measurable organ outcome coincide, as in congenital hypogonadotrophic hypogonadism and in rodent models of neonatal gonadotrophin withdrawal. Evidence is considerably weaker for population-level claims that environmental exposures act principally through central rather than gonadal mechanisms, because most human studies are observational, exposure assessment is imprecise, and central and peripheral effects are rarely separable with the measures available. The critical appraisal identifies three persistent problems: reliance on rodent models whose minipuberty differs in duration and hormonal profile from that of humans; the near absence of prospective cohorts linking quantified infantile hormone exposure to adult fertility outcomes; and conflation of statistical association with developmental causation. Priorities for future work include long-term follow-up of infants receiving neonatal gonadotrophin replacement, cell-type-resolved developmental atlases of the human hypothalamus, and study designs capable of distinguishing central from intragonadal programming.