Global Birth Hypoxia Increases the Neonatal Testosterone Surge in the Rat

Abstract

Background/Aims: Global birth hypoxia in rats has been shown to produce long-term changes in central nervous system functions, known to be influenced by neonatal testosterone secretion. Birth hypoxia alters levels of several circulating hormones, but it is unknown if it affects neonatal testosterone. Methods: Using a rat model of acute global hypoxia during cesarean section (C-section) birth, this study tested whether birth hypoxia affects neonatal testosterone. We then evaluated whether the observed hypoxia-induced changes in neonatal testosterone may be mediated via N-methyl-D-aspartate (NMDA) receptor activation and/or altered luteinizing hormone (LH), adrenocorticotropic hormone (ACTH) or corticosterone levels. Longer-term effects of birth hypoxia on testosterone-related function were also assessed. Results: Rats born by C-section + 15 min of anoxia had significantly higher plasma testosterone at 2 and 3 h after birth compared to controls born either vaginally or by C-section. Administration of an NMDA receptor antagonist at birth increased neonatal testosterone in both anoxic pups and controls. Pups exposed to birth anoxia under hypothermic conditions also showed increased neonatal testosterone. Circulating LH, follicle-stimulating hormone and corticosterone in neonates, and testosterone at adulthood were unaffected by birth hypoxia. However, plasma ACTH was significantly increased in anoxic neonates at 2 h after birth. Birth condition had no effect on anogenital distance or juvenile play behavior. Conclusion: It is concluded that birth hypoxia augments plasma testosterone during the critical period of the neonatal testosterone surge, by a mechanism that is independent of NMDA-mediated LH secretion, but may involve increased circulating ACTH.