The placental programming hypothesis: placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders

Polypeptide hormones and steroid hormones, either expressed by the placenta or dependant on the placenta for their synthesis, are key to driving adaptations in the mother during pregnancy that support growth in utero. These adaptations include changes in maternal behaviour that take place in pregnancy and after the birth to ensure that offspring receive appropriate care and nutrition. Placentally-derived hormones implicated in the programming of maternal caregiving in rodents include prolactin-related hormones and steroid hormones. Neuromodulators produced by the placenta may act directly on the fetus to support brain development. A number of imprinted genes function antagonistically in the placenta to regulate the development of key placental endocrine lineages expressing these hormones. Gain-in-expression of the normally maternally expressed gene Phlda2 or loss-of-function of the normally paternally expressed gene Peg3 results in fewer endocrine cells in the placenta, and pups are born low birth weight. Importantly, wild type dams carrying these genetically altered pups display alterations in their behaviour with decreased focus on nurturing (Phlda2) or heightened anxiety (Peg3). These same genes may regulate placental hormones in human pregnancies, with the potential to influence birth weight and maternal mood. Consequently, the aberrant expression of imprinted genes in the placenta may underlie the reported co-occurrence of low birth weight with maternal prenatal depression

Effect of toothbrushing duration and dentifrice quantity on enamel remineralisation: An in situ randomized clinical trial

Objectives The influence of toothbrushing duration and dentifrice quantity on fluoride efficacy against dental caries is poorly understood. This study investigated effects of these two oral hygiene factors on enamel remineralisation (measured as surface microhardness recovery [SMHR]), enamel fluoride uptake (EFU), and net acid resistance (NAR) post-remineralisation in a randomized clinical study using an in situ caries model. Methods Subjects (n = 63) wore their partial dentures holding partially demineralised human enamel specimens and brushed twice-daily for two weeks, following each of five regimens: brushing for 120 or 45 s with 1.5 g of 1150 ppm F (as NaF) dentifrice; for 120 or 45 s with 0.5 g of this dentifrice; and for 120 s with 1.5 g of 250 ppm F (NaF) dentifrice. Results Comparing brushing for 120 s against brushing for 45 s, SMHR and EFU increased by 20.0% and 26.9% respectively when 1.5 g dentifrice was used; and by 22.8% and 19.9% respectively when 0.5 g dentifrice was used. Comparing brushing with 1.5 g against brushing with 0.5 g dentifrice, SMHR and EFU increased by 35.3% and 51.3% respectively when brushing for 120 s, and by 38.4% and 43.0% respectively when brushing for 45 s. Increasing brushing duration and dentifrice quantity also increased the NAR value. The effects of these two oral hygiene factors on SMHR, EFU, and NAR were statistically significant (p < 0.05 in all cases). Conclusion Brushing duration and dentifrice quantity have the potential to influence the anti-caries effectiveness of fluoride dentifrices. Study NCT01563172 on ClinicalTrials.gov. Clinical significance The effect of two key oral hygiene regimen factors – toothbrushing duration and dentifrice quantity – on fluoride’s anticaries effectiveness is unclear. This 2-week home-use in situ remineralisation clinical study showed both these factors can influence fluoride bioactivity, and so can potentially affect fluoride’s ability to protect against caries

Imprinted genes influencing the quality of maternal care

In mammals successful rearing imposes a cost on later reproductive fitness specifically on the mother creating the potential for parental conflict. Loss of function of three imprinted genes in the dam result in deficits in maternal care suggesting that, like maternal nutrients, maternal care is a resource over which the parental genomes are in conflict. However, the induction of maternal care is a complex and highly regulated process. Unsurprisingly many gene disruptions, as well as adverse environmental exposures in pregnancy, result in maternal care deficits. Recent compelling evidence for a more purposeful imprinting phenomenon comes from studying the impact of two imprinted genes, Phlda2 and Peg3, expressed in the placenta on the mother’s behaviour. The explicit demonstration that imprinted genes expressed in the offspring influence maternal behaviour lends significant weight to the hypothesis that maternal care is a resource that has been manipulated by the paternal genome

Assessing sedimentation equilibrium profiles in analytical ultracentrifugation experiments on macromolecules: from simple average molecular weight analysis to molecular weight distribution and interaction analysis

Molecular weights (molar masses), molecular weight distributions, dissociation constants and other interaction parameters are fundamental characteristics of proteins, nucleic acids, polysaccharides and glycoconjugates in solution. Sedimentation equilibrium in the analytical ultracentrifugation provides a powerful method with no supplementary immobilization, columns or membranes required. It is particularly powerful when used in conjunction with its sister technique, namely sedimentation velocity analysis. We describe key approaches now available and their application to the characterisation of antibodies polysaccharides and glycoconjugates. We indicate how major complications such as thermodynamic non-ideality can now be routinely dealt with, thanks to a great extent to the extensive contribution of Professor DonWinzor over several decades of research

Loss of offspring Peg3 reduces neonatal ultrasonic vocalizations and increases maternal anxiety in wild-type mothers

Depression and anxiety are the most common mental health conditions during pregnancy and can impair the normal development of mother-infant interactions. These adversities are associated with low birth weight and increased risk of behavioural disorders in children. We recently reported reduced expression of the imprinted gene PATERNALLY EXPRESSED GENE 3 (PEG3) in placenta of human infants born to depressed mothers. Expression of Peg3 in brain has previously been linked maternal behaviour in rodents, at least in some studies, with mutant dams neglecting their pups. However, in our human study decreased expression was in the placenta derived from the fetus. Here, we examined maternal behaviour in response to reduced expression of Peg3 in the feto-placental unit. Prenatally we found novelty reactivity was altered in wildtype females carrying litters with a null mutation in Peg3. This behavioural alteration was short-lived and there were no significant differences the transcriptomes of either the maternal hypothalamus or hippocampus at E16.5. In contrast, while maternal gross maternal care was intact postnatally, the exposed dams were significantly slower to retrieve their pups and displayed a marked increase in anxiety. We also observed a significant reduction in the isolation-induced ultrasonic vocalisations (USVs) emitted by mutant pups separated from their mothers. USVs are a form of communication known to elicit maternal care suggesting Peg3 mutant pups drive the deficit in maternal behaviour. These data support the hypothesis that reduced placental PEG3 in human pregnancies occurs as a consequence of prenatal depression but leaves scope for feto-placental Peg3 dosage, during gestation, influencing aspects of maternal behaviour