Session: OR04-GnRH & Gonadotroph Biology & Signaling
Room 135 (Moscone Center)
The Tac2 deficient state was confirmed by an absence of NKB immunoreactivity (Novus Biological, 1:1000) in the arcuate nucleus. Compared to controls, Tac2-/- females demonstrated delayed vaginal opening (P 25.1 ± 0.6 vs. P 27.4 ± 0.9; p<0.05) and time to first estrus (P 31.3 ± 1.3 vs. P 41.9 ± 2.7; p<0.01). In addition, Tac2-/- females had significantly longer cycle lengths (4.4 ± 0.2 days vs. 12.4 ± 0.9 days; p<0.001). Despite the abnormalities in estrous cyclicity, all Tac2-/- females achieved pregnancy when placed in a cage with WT or Tac2-/- males. Although the time to preputial separation, anogenital distance and testicular weight were all suggestive of an abnormal reproductive phenotype in Tac2-/- males, these differences were not statistically different from littermate controls.
Tac2-/- females have delayed time to vaginal opening, delayed first estrous, and abnormal cycling compared to WT littermates, but seemingly robust fertility. Whereas both Tac2-/- and Tacr3-/- mice have abnormal estrus cycling, only Tac2-/- mice have significant delays in sexual maturation. Though subtle background differences between different B6/129 hybrid lines cannot be excluded, this unexpected difference in the timing of sexual maturation between Tac2-/- and Tacr3-/- female animals suggests that neurokinin B may signal through multiple tachykinin receptors to modulate the hypothalamic-pituitary-gonadal axis. Tac2-/- mice have parallels to humans with reversible hypogonadotropism, with defects in sexual maturation but recovery of reproductive function and fertility in adulthood.
Nothing to Disclose: SNA, CT, MFL, YMC, SBS
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