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Until the introduction of Assisted Reproductive Technologies (ART), many studies were conducted in order to evaluate their impact upon the children's health born in such a way. The epigenetic-risk notion was invoked and a link between ART and diseases associated with imprinting alterations was suggested with different examples, such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Silver-Russell syndrome (SRS). The epigenetic “life cycle” of imprinting (germline erasure, germline establishment, and somatic maintenance) concerns all the phases from gametogenesis, gamete maturation, fertilization, to early embryo development and appears particularly vulnerable to perturbations induced by superovulation, in vitro fertilization, embryo culture and embryo transfer. The studies, performed in model animal, provide a basis of the understanding of imprinting alterations induced by the ART and clinically useful information in order to improve the ART. [Copyright &y& Elsevier]

Lactation performance is dependent on both the genetic characteristics and the environmental conditions surrounding lactating cows. However, individual variations can still be observed within a given breed under similar environmental conditions. The role of the environment between birth and lactation could be better appreciated in cloned cows, which are presumed to be genetically identical, but differences in lactation performance between cloned and noncloned cows first need to be clearly evaluated. Conflicting results have been described in the literature, so our aim was to clarify this situation. Nine cloned Prim' Holstein cows were produced by the transfer of nuclei from a single fibroblast cell line after cell fusion with enucleated oocytes. The cloned cows and 9 noncloned counterparts were raised under similar conditions. Milk production and composition were recorded monthly from calving until 200 d in milk. At 67 d in milk, biopsies were sampled from the rear quarter of the udder, their mammary epithelial cell content was evaluated, and mammary cell renewal, RNA, and DNA were then analyzed in relevant samples. The results showed that milk production did not differ significantly between cloned and noncloned cows, but milk protein and fat contents were less variable in cloned cows. Furthermore, milk fat yield and contents were lower in cloned cows during early lactation. At around 67 DIM, milk fat and protein yields, as well as milk fat, protein, and lactose contents, were also lower in cloned cows. These lower yields could be linked to the higher apoptotic rate observed in cloned cows. Apoptosis is triggered by insulin-like factor growth binding protein 5 (IGFBP5) and plasminogen activator inhibitor (PAI), which both interact with CSN1S2. During our experiments, CSN1S2 transcript levels were lower in the mammary gland of cloned cows. The mammary cell apoptotic rate observed in cloned cows may have been related to the higher levels of DNA (cytosine-5-)- methyltransferase 1 (DNMT1) transcripts, coding for products that maintain the epigenetic status of cells. We conclude, therefore, that milk production in cloned cows differs slightly from that of noncloned cows. These differences may be due, in part, to a higher incidence of subclinical mastitis. They were associated with differences in cell apoptosis and linked to variations in DNMT1 mRNA. However, milk protein and fat contents were more similar among cloned cows than among noncloned cows. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the influence of growth hormone treatment and milking frequency on mammary gland morphology and milk composition of ruminants. Review of related literature; Materials and methods used; Results and discussion.

Presents information on a study which examined the efficacy of using somatic cells from goat milk for dynamic studies of gene expression in the mammary gland. Materials and methods used in the study; Results and discussion.

A letter to the editor is presented regarding the Fas expression at diagnosis as a biomarker of the activity of azacitidine in advanced myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML).

An abstract of the study "Investigation of Inter-Individual Epigenetic Variability in Bovine Clones: A High Throughput Study," by H. Kiefer et al, is presented.

Since the first success in sheep, the production of viable cloned offspring by somatic cell nuclear transfer (SCNT) is still doomed by a high incidence of pregnancy failure. In cattle, most gestation losses initially take place during the peri-implantation period. Then, abnormal placentation associated with fetal overgrowth (abnormal offspring syndrome) occurs in late pregnancy. As a consequence, IETS recommendations include regular ultrasound evaluation of SCNT pregnancies, with qualitative ultrasound evaluation of the placentomes, fetal movements and fluids being proposed. The objective of this study was to evaluate the use of new, quantitative parameters for the assessment of feto-placental development in AI and SCNT bovine pregnancies. Twenty-two heifers of 4 different breeds were used as SCNT recipients and 11 Holstein heifers were used as AI controls (C). All SCNT fetuses were produced as previously published in the laboratory, using the same fibroblast donor. Animals were scanned every 2 weeks from Day 150 using a Voluson-i (GE Medical Systems) with a transabdominal multifrequency probe (2.2 to 6.5 MHz), allowing automatic 3D volume and Doppler acquisition. Each time, 7 placentomes were scored from 0 to 3 according to echogenicity, general appearance and degree of oedema and their 2D surface was measured. Fetal intercostal width (ICW) was measured in a coronal view just behind the heart. Doppler velocimetry indices, pulsatility index (PI) and resistance index (RI) of one of the two fetal umbilical arteries were obtained and the diameters of the umbilical vessels were measured (UD). The 3D power Doppler was performed to obtain vascular index (VI), flow index (FI) and vascular flow index (VFI). Data were analysed by ANOVA with GraphPad Prism®. So far, 27 heifers have either delivered (n = 10 SCNT and 7 C) or pregnancies have been terminated because of abnormal offspring syndrome (n = 10 SCNT). One thousand five hundred and 197 placentomes have been analysed for 2D and 3D analyses, respectively. The mean placentome score is significantly higher (less normal) in SCNT compared with C (P < 0.0001) but does not vary according to gestational age. The placentome surface is also significantly larger in SCNT vs C (P < 0.0001) but also in SCNT that did not go to term vs those that were alive at birth (P < 0.002). Fetal ICW and UD are consistently larger in SCNT vs C (P < 0.0001) at all stages of pregnancy and there is a significant correlation (r2 = 0.81) between ICW at 15 days before term and birth weight. The PI and RI were not different between SCNT and C. Intra-operator reproducibility of 3D analyses was very high (intra-class correlation coefficient: 80 to 95% for a 95% confidence interval). There was no significant difference for VI, FI, or VFI between SCNT and C. Ongoing work taking into account pregnancy outcomes indicates that placentome scores are useful indicators of pregnancy outcome in SCNT pregnancies. In contrast, the abnormal vascularization observed by histology in SCNT placentomes does not appear to be accompanied by abnormal placental blood flow when analysed using quantitative 3D Doppler. This project received financial support from ANR (ref. PCS-09-GENM-022). [ABSTRACT FROM AUTHOR]