Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mice and men.

Patients bearing mutations in TAC3 and TACR3 (which encode neurokinin B and its receptor, respectively) have sexual infantilism and infertility due to GnRH deficiency. In contrast, Tacr3(-/-) mice have previously been reported to be fertile. Because of this apparent phenotypic discordance between mice and men bearing disabling mutations in Tacr3/TACR3, Tacr3 null mice were phenotyped with close attention to pubertal development, estrous cyclicity, and fertility.

Assessing reproductive status/stages in mice.

The short reproductive cycle length observed in rodents, called the estrous cycle, makes them an ideal animal model for investigation of changes that occur during the reproductive cycle. Most of the data in the literature about the estrous cycle is obtained from rats because they are easily manipulated and they exhibit a clear and well-defined estrous cycle. However, the increased number of experiments using knockout mice requires identification of their estrous cycle as well, since (in)fertility issues may arise.

Kisspeptin-10 facilitates a plasma membrane-driven calcium oscillator in gonadotropin-releasing hormone-1 neurons.

Kisspeptins, the natural ligands of the G-protein-coupled receptor (GPR)-54, are the most potent stimulators of GnRH-1 secretion and as such are critical to reproductive function. However, the mechanism by which kisspeptins enhance calcium-regulated neuropeptide secretion is not clear. In the present study, we used GnRH-1 neurons maintained in mice nasal explants to examine the expression and signaling of GPR54.