Embryonic factors mediate the maternal age-induced programming of offspring postnatal behavior in mice†.

Advanced maternal age is associated with adverse pregnancy and offspring outcomes, including neurodevelopmental disorders. While age-related oocyte and embryonic abnormalities may underlie this association, the aged maternal uterine environment also plays an important role in offspring development and survival. The aim of this study was to evaluate the contribution of maternal age-related embryonic and uterine factors on pregnancy and offspring behavior, by using a model of reciprocal embryo transfer between old and young female mice. Pregnancies were obtained by transferring embryos collected from either old (9-14 months) or young (3-4 months) C57BL/6J female mice to either young or old recipients. The results showed that embryos from old and young donors have comparable developmental potential when transferred to young recipients, whereas no pregnancies were obtained by transferring embryos of young females to old recipients. Moreover, the offspring conceived by aged females displayed altered ultrasonic vocalization and learning skills compared to the progeny of young females, even though they were both prenatally and postnatally fostered by young recipients. These results indicate that maternal factors mostly determine the occurrence of age-related pregnancy complications, whereas the long-term effects of maternal aging on the offspring's behavior could be already established at pre-implantation stages and depend on embryonic factors.

Delayed parenthood and its influence on offspring health: what have we learned from the mouse model†.

Delayed parenthood is constantly increasing worldwide due to various socio-economic factors. In the last decade, a growing number of epidemiological studies have suggested a link between advanced parental age and an increased risk of diseases in the offspring. Also, poor reproductive outcome has been described in pregnancies conceived by aged parents. Similarly, animal studies showed that aging negatively affects gametes, early embryonic development, pregnancy progression, and the postnatal phenotype of resulting offspring. However, how and to what extent parental age is a risk factor for the health of future generations is still a subject of debate. Notwithstanding the limitation of an animal model, the mouse model represents a useful tool to understand not only the influence of parental age on offspring phenotype but also the biological mechanisms underlying the poor reproductive outcome and the occurrence of diseases in the descendants. The present review aims at i) providing an overview of the current knowledge from mouse model about the risks associated with conception at advanced age (e.g. neurodevelopmental and metabolic disorders), ii) highlighting the candidate biological mechanisms underlying this phenomenon, and iii) discussing on how murine-derived data can be relevant to humans.

In Vitro Studies concerning Selected Properties of a Composite Material Blended with Nanofluoroapatite Crystals.

The aim of the paper was to determine the potential for fluorine release from an original composite material blended with nanofluoroapatite (FAp). The level of fluoride ion emission into deionized water and saline was studied over a period of 12 weeks. Values were recorded after 1, 3, 24, 48, 72, and 96 h and then weekly for a period of 12 weeks. There were statistically significant differences in the periods of fluoride ion release from 5%FAp and 2%FAp materials into saline solution as well as into deionized water. The highest fluorine release from 5%FAp + polymer was observed in the 10th and 11th week of incubation (for saline solution) and in the 9th, 10th, and 11th week (for deionized water). The highest fluorine release from 2%FAp + polymer was observed in the 9th, 11th, and 12th week of incubation for both environments. Total fluoride ion release from 5%FAp + polymer and mean fluoride release levels were similar in 5%FAp and 2%FAp in both environments. Both tested materials (5%FAp and 2%FAp) show the ability to release fluoride ions over a long time in the experimental environment.

Assessment of Microstructure and Release of Fluoride Ions from Selected Fissure Sealants: An In Vitro Study.

The aim of this study was to compare fluoride release from four selected fissure sealants: fissure sealant manufactured by Arkona, Helioseal F, Helioseal F Plus, and Conseal. Tested parameters included emission of fluoride ions into saline (0.9% NaCl) and deionized water over a period of 2 weeks. Values were recorded after 1, 3, 24, 48, 72, and 96 h, and then after 1 and 2 weeks. All sealants were characterized by a constant fluoride release level. The highest fluoride release level was noted for Conseal (0.0169 ppm/mg), while the lowest was noted for fissure sealant manufactured by Arkona (0.063 ppm/mg). Fissure sealants, which contain fluoride, release it not only during polymerization, but also for several days after application. The use of fissure sealants whose composition includes fluoride is an effective method of preventing tooth decay.

Preconceptional Resveratrol Supplementation Partially Counteracts Age-Related Reproductive Complications in C57BL/6J Female Mice.

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

Blastomere removal affects homeostatic control leading to obesity in male mice.

Preimplantation embryos are particularly vulnerable to environmental perturbations, including those related to assisted reproductive technologies. Invasive embryo manipulations, such as blastomere biopsy, are applied worldwide in clinical settings for preimplantation genetic testing. Mouse models have previously shown that blastomere biopsy may be associated with altered phenotypes in adult offspring. The aim of the present study was to investigate the specific contribution of blastomere removal to the physiological, behavioral, and molecular regulators of energy homeostasis, as compared to sham manipulation (re-introducing the blastomere into the embryo after its removal) and in vitro culture. Mice derived from 8-cell embryos subjected to blastomere removal displayed: (i) higher body weight and adiposity, (ii) increased food intake and sucrose preference, (iii) decreased time of immobility in the tail suspension test, and (iv) resistance to weight loss after social isolation or following 3 days of physical exercise - compared to mice derived from sham biopsy or from in vitro-cultured embryos. Mice generated after blastomere removal also had increased circulating leptin and leptin gene expression in adipose tissue, as well as increased ghrelin receptor gene expression in the hypothalamus, compared to control mice. The effects of blastomere biopsy on offspring phenotype were sexually dimorphic, with females not being affected. These results indicate that blastomere deprivation, rather than other perturbations of the blastomere biopsy procedure, programs male embryos to develop physiological, behavioral, and molecular dysregulation of energy homeostasis, leading to postnatal obesity.