Aberrant early in life stimulation of the stress-response system affects emotional contagion and oxytocin regulation in adult male mice

Results over the last decades have provided evidence suggesting that HPA axis dysfunction is a major risk factor predisposing to the development of psychopathological behaviour. This susceptibility can be programmed during developmental windows of marked neuroplasticity, allowing early-life adversity to convey vulnerability to mental illness later in life. Besides genetic predisposition, also environmental factors play a pivotal role in this process, through embodiment of the mother’s emotions, or via nutrients and hormones transferred through the placenta and the maternal milk. The aim of the current translational study was to mimic a severe stress condition by exposing female CD-1 mouse dams to abnormal levels of corticosterone (80 µg/mL) in the drinking water either during the last week of pregnancy (PreCORT) or the first one of lactation (PostCORT), compared to an Animal Facility Rearing (AFR) control group. When tested as adults, male mice from PostCORT offspring and somewhat less the PreCORT mice exhibited a markedly increased corticosterone response to acute restraint stress, compared to perinatal AFR controls. Aberrant persistence of adolescence-typical increased interest towards novel social stimuli and somewhat deficient emotional contagion also characterised profiles in both perinatal-CORT groups. Intranasal oxytocin (0 or 20.0 µg/kg) generally managed to reduce the stress response and restore a regular behavioural phenotype. Alterations in density of glucocorticoid and mineralocorticoid receptors, oxytocin and µ- and κ-opioid receptors were found. Changes differed as a function of brain areas and the specific age window of perinatal aberrant stimulation of the HPA axis. Present results provided experimental evidence in a translational mouse model that precocious adversity represents a risk factor predisposing to the development of psychopathological behaviour

The mosaic embryo: what it means for the doctor and the patient

Introduction: Mosaic embryos are embryos that on preimplantation genetic analysis are found to be composed of euploid and aneuploid cells. Although most of these embryos do not implant when transferred into the uterus following IVF treatment, some may implant and are capable of giving rise to babies. Evidence acquisition: There is currently an increasing number of reports of live births following the transfer of mosaic embryos. Compared to euploid, mosaic embryos have lower implantation rates and higher rates of miscarriage, and occasionally aneuploid component persists. However, their outcome is better than that obtained after the transfer of embryos consisting entirely of aneuploid cells. After implantation, the ability to develop into a full-term pregnancy is influenced by the amount and type of chromosomal mosaicism present in a mosaic embryo. Nowadays many experts in the reproductive field consider mosaic transfers as an option when no euploid embryos are available. Genetic counseling is an important part of educating patients about the likelihood of having a pregnancy with healthy baby but also on the risk that mosaicism could persist and result in liveborn with chromosomal abnormality. Each situation needs to be assessed on a case-by-case basis and counseled accordingly. Evidence synthesis: So far, the transfers of 2155 mosaic embryos have been documented and 440 live births resulting in healthy babies have been reported. In addition, in the literature to date, there are 6 cases in which embryonic mosaicism persisted. Conclusions: In conclusion, the available data indicate that mosaic embryos have the potential to implant and develop into healthy babies, albeit with lower success rates than euploids. Further clinical outcomes should be collected to better establish a refined ranking of embryos to transfer