Stress and reproduction: Controversies and challenges

Inhibition of reproductive function by the activation of the stress–response has been observed since times of antiquity, however delineating a molecular mechanism by which this occurs in vertebrates continues to present a major challenge. Because recent genome sequencing programs have identified the presence of numerous paralogous peptides and receptors, our understanding of the complexity of the interaction between the reproductive and stress axes has expanded. At the neuroendocrine level, numerous studies have focused on the interaction between the corticotropin-releasing factor (CRF) and gonadotropin-releasing hormone (GnRH) systems in vertebrates. Moreover, most of these studies have been performed using rodent models and may not be completely relevant for non-mammalian vertebrates. A further problem lies in the variation of the functional expression of paralogous genes in the different taxa. In particular, the urocortin 2 and GnRH-II systems have been lost in some lineages, where its function has been taken over by urocortin 3 and GnRH-I, respectively. Establishing an integrated model that incorporates all paralogous systems for both the stress and reproductive system remains to be achieved.

► Unequivocal direct interaction between CRF and GnRH-1 remains unresolved.
► Direct interaction among urocortins and urotensin-I with GnRH-I and -II is poorly understood.
► Urocortin 2 and GnRH-II systems have been lost in a number of vertebrate lineages.
► Epigenetic effects account for some stress and reproduction interactions in mammals and birds.