In mammals, lactation is associated with a period of
infertility characterized by the loss of pulsatile secretion of
GnRH and cessation of ovulatory cycles. Despite the importance of lactational
infertility in determining overall fecundity of a species, the mechanisms by which the suckling stimulus suppresses
GnRH secretion remain unclear. Because
kisspeptin neurons are critical for fertility, the aim of this study was to test the hypothesis that reduced
kisspeptin expression might mediate the lactation-induced suppression of fertility, using mouse models. In the rostral periventricular area of the third ventricle (RP3V), a progressive decrease in RP3V Kiss1
mRNA levels was observed during pregnancy culminating in a 10-fold reduction during lactation compared with diestrous controls. This was associated with approximately 60% reduction in the numbers of
kisspeptin-immunoreactive neurons in the RP3V detected during lactation. Similarly, in the arcuate nucleus there was also a significant decrease in Kiss1
mRNA levels during late pregnancy and midlactation, and a notable decrease in
kisspeptin fiber density during lactation. The functional characteristics of the RP3V
kisspeptin input to
GnRH neurons were assessed using electrophysiological approaches in an acute brain slice preparation. Although endogenous RP3V
kisspeptin neurons were found to activate
GnRH neurons in diestrous mice, this was never observed during lactation. This did not result from an absence of
kisspeptin receptors because
GnRH neurons responded normally to 100 nM exogenous
kisspeptin during lactation. The
kisspeptin deficit in lactating mice was selective, because
GnRH neurons responded normally to RP3V gamma aminobutryic
acid inputs during lactation. These data demonstrate that a selective loss of RP3V
kisspeptin inputs to
GnRH neurons during lactation is the likely mechanism causing lactational
anovulation in the mouse.