Noradrenergic nuclei that receive sensory input during mating and project to the ventromedial hypothalamus play a role in mating-induced pseudopregnancy in the female rat.

In female rats, vaginal-cervical stimulation (VCS) received during mating induces bicircadian prolactin surges that are required for the maintenance of pregnancy or pseudopregnancy (PSP). The neural circuits that transmit VCS inputs to the brain have not been fully described, although mating stimulation is known to activate medullary noradrenergic cell groups that project to the forebrain. In response to VCS, these neurones release noradrenaline within the ventrolateral division of the ventromedial hypothalamus (VMHvl) and the posterodorsal medial amygdala (MePD), two forebrain sites that are implicated in the initiation of PSP. Noradrenaline receptor activation within the VMHvl is both necessary and sufficient for PSP induction, suggesting that noradrenaline acting within the VMHvl is particularly important in mediating the effects of VCS towards the establishment of PSP. We therefore investigated whether or not endogenous, VCS-induced noradrenaline release within the VMHvl is involved in PSP induction in the rat. Before the receipt of sufficient mating stimulation to induce PSP, a retrograde neurotoxin, dopamine-ß-hydroxylase-saporin (DBH-SAP), was infused bilaterally into the either the VMHvl or the MePD to selectively destroy afferent noradrenergic nuclei in the brainstem. DBH-SAP infusions into the VMHvl lesioned mating-responsive noradrenergic neurones in A1 and A2 medullary nuclei and reduced the incidence of PSP by 50%. Infusions of DBH-SAP into the MePD had no effect on the subsequent induction of PSP. These results suggest that VCS is conveyed to mating-responsive forebrain areas by brainstem noradrenergic neurones, and that the activity of noradrenergic cells projecting to the VMHvl is involved in the induction of PSP.

SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts.

Although selection of chromosomally normal embryos has the potential to improve outcomes for patients undergoing IVF, the clinical impact of aneuploidy screening by fluorescence in situ hybridization (FISH) has been controversial. There are many putative explanations including sampling error due to mosaicism, negative impact of biopsy, a lack of comprehensive chromosome screening, the possibility of embryo self-correction and poor predictive value of the technology itself. Direct analysis of the negative predictive value of FISH-based aneuploidy screening for an embryo's reproductive potential has not been performed. Although previous studies have found that cleavage-stage FISH is poorly predictive of aneuploidy in morphologically normal blastocysts, putative explanations have not been investigated. The present study used a single nucleotide polymorphism (SNP) microarray-based 24 chromosome aneuploidy screening technology to re-evaluate morphologically normal blastocysts that were diagnosed as aneuploid by FISH at the cleavage stage. Mosaicism and preferential segregation of aneuploidy to the trophectoderm (TE) were evaluated by characterization of multiple sections of the blastocyst. SNP microarray technology also provided the first opportunity to evaluate self-correction mechanisms involving extrusion or duplication of aneuploid chromosomes resulting in uniparental disomy (UPD). Of all blastocysts evaluated (n = 50), 58% were euploid in all sections despite an aneuploid FISH result. Aneuploid blastocysts displayed no evidence of preferential segregation of abnormalities to the TE. In addition, extrusion or duplication of aneuploid chromosomes resulting in UPD did not occur. These findings support the conclusion that cleavage-stage FISH technology is poorly predictive of aneuploidy in morphologically normal blastocysts.

Noradrenergic innervation of the ventromedial hypothalamus is involved in mating-induced pseudopregnancy in the female rat.

The ventromedial hypothalamus (VMH) is an oestrogen-responsive area known to facilitate female sexual behaviour in the rat. The VMH is innervated by noradrenergic neurones projecting from the brain stem, and it has been demonstrated that noradrenaline receptor activation in the VMH plays a role in the expression of the lordosis reflex. Noradrenaline has been shown to be released within the VMH after a female receives vaginocervical stimulation (VCS) from the male during mating. VCS also is required to induce twice-daily surges of prolactin (PRL) characteristic of early pregnancy or pseudopregnancy (PSP). To determine whether noradrenaline within the ventrolateral ventromedial hypothalamus (VMHvl) plays a facilitatory role in initiation of PSP, we administered the alpha(1)-noradrenergic receptor agonist, phenylephrine, and the alpha(2)-autoreceptor antagonist, yohimbine, unilaterally into the VMHvl. Phenylephrine stimulated PSP in 85.7% of females given an amount of VCS known to be subthreshold for the induction of PSP, whereas saline infusion (0%) or cannula misplacement (7.7%) were ineffective. Yohimbine had a similar effect, inducing PSP in 85.7% of females, whereas 7.6% of both control groups together showed PSP. Finally, bilateral blockade of alpha(1)-receptors using prazosin blocked PSP in 100% of females given sufficient VCS to induce PSP, whereas saline infusion or misplaced intracerebral cannulae failed to prevent PSP in any animal. In all experiments, vaginal dioestrous was indicative of PSP, in that animals showed a mean number of days between oestrus of 12.8 +/- 0.9. The results of the study demonstrate an important role for the VMHvl in initiation of PSP and suggest that the release of noradrenaline in the VMHvl at the time of mating contributes to neuroendocrine mechanisms responsible for establishing PSP in the female rat.