Restricted exposure of mice to primer pheromones coincident with prolactin surges blocks pregnancy by changing hypothalamic dopamine release

Abstract

Summary. Exposure of recently mated female mice to strange male urine revealed that exposure for 8 h was sufficient to produce pregnancy block providing exposure is for two 4-h periods coincident with prolactin surges. Exposure for 8 h between prolactin surges or one 4-h exposure coincident with either the nocturnal or the diurnal prolactin surge was without effect. When bromocriptine, a dopamine agonist, was given coincident with the nocturnal and diurnal prolactin surges, it was equally effective, but the opiate antagonist (naltrexone) administered in a similar manner was without effect. This result indicates that pheromonal action is through excitation of the tuberoinfundibular neurones rather than by inhibition of \g=b\-endorphin neurones. Further evidence for dopamine involvement in pregnancy block is demonstrated by showing DOPA accumulation in the medio-basal hypothalamus following exposure to male urinary pheromones after dihydroxybenzylhydrazine (DHBH) administration, which blocks the enzyme DOPA-decarboxylase. Taken together, this series of experiments provides convincing evidence for the dopamine inhibition of prolactin release being the final pathway for pheromone action in the context of pregnancy block.

The vomeronasal system

“…It is also consistent with the finding that the exposure of male hamsters to urine from female hamsters decreases the length of the postsynaptic densities of the excitatory, glutamatergic synapses from mitral to granule cells [84]. Such a 'windup' of mitral cell transmission may be important in maintaining a response to the pheromones during the long periods of exposure that are necessary for their primer pheromonal effects [52]. Taken together, these various lines of evidence suggest that synaptic plasticity of the reciprocal synapses between mitral and granule cells in the AOB may play a vital role in controlling the central transmission of the pheromonal signal.…”

“…Vomeronasal receptor neurons respond to maintained current injection with steady trains of action potentials with little sign of adaptation, in contrast to the rapid adaptation seen in olfactory receptor neurons [51]. This is consistent with the prolonged periods of exposure required to induce the endocrinological effects of rodent primer pheromones [52]. Additionally, a maintained level of activity in VRNs due to continuous pheromonal exposure could be subject to inhibitory interactions with other pheromonal stimuli at the level of the receptor neuron.…”

Stress lowers the threshold dose at which bisphenol A disrupts blastocyst implantation, in conjunction with decreased uterine closure and e-cadherin

“…Under some circumstances, exogenous P 4 can to some degree counteract the influence of stressors, but those effects are incomplete [10] or conditional on concurrent E 2 levels [8] and may be pharmacological rather than physiological. A contribution of P 4 to the Bruce effect has been posited to occur in response to prolactin suppression during novel male exposure in the Bruce effect [44,63,64]; however the evidence is arguably incomplete [24]. In the case of stress-induced early pregnancy failure, there are also likely stressor-specific factors, and there is also evidence for a role of immune factors, albeit more during the post-implantation period [65,66].…”

Towards an understanding of the pregnancy-blocking urinary chemosignals of mice

“…Therefore the timing of exposure to the male urine is important for its effectiveness in blocking pregnancy. Two 4 h periods of exposure to male urine, or two 5 min periods of electrical stimulation of the AOB, are sufficient to block pregnancy, provided that they are coincident with the prolactin peaks [10,11]. In contrast, the same amount of exposure or AOB stimulation given between the prolactin peaks is ineffective.…”