We analyzed the change in gene expression related to dam physiological status in day (D)18 embryos from growing heifers (GH), early lactating cows (ELC), and late lactating cows (LLC). Dam energy metabolism was characterized by measurement of circulating concentrations of insulin, glucose, IGF-1, nonesterified fatty acids, ␤-hydroxybutyrate, and urea before embryo flush. The metabolic parameters were related to differential gene expression in the extraembryonic tissues by correlation analysis. Embryo development estimated by measuring the length of the conceptuses and the proportion of expected D18 gastrulating stages was not different between the three groups of females. However, embryo metabolism was greatly affected by dam physiological status when we compared GH with ELC and GH with LLC but to a lesser extent when ELC was compared with LLC. Genes involved in glucose, pyruvate, and acetate utilization were upregulated in GH vs. ELC conceptuses (e.g., SLC2A1, PC, ACSS2, ACSS3). This was also true for the pentose pathway (PGD, TKT), which is involved in synthesis of ribose precursors of RNA and DNA. The pathways involved in lipid synthesis were also upregulated in GH vs. ELC. Despite similar morphological development, the molecular characteristics of the heifers' embryos were consistently different from those of the cows. Most of these differences were strongly related to metabolic/hormone patterns before insemination and during conceptus free-life. Many biosynthetic pathways appeared to be more active in heifer embryos than in cow embryos, and consequently they seemed to be healthier, and this may be more conducive to continue development. dairy cow; fertility; energy balance; energy metabolism; conceptus development; gene expression; correlations IN THE MODERN HOLSTEIN cow, calving rates are close to 55-60% in heifers and 35-40% in lactating cows (39,73). Most pregnancy losses occur prior to the period of maternal recognition and maintenance of the corpus luteum, i.e., before days 15-17 (D15-D17) after artificial insemination (AI), and are due to nonfertilization-early embryonic loss (NF-EEL, Refs. 22,35,73). NF-EEL can be estimated in field trials by measuring plasma or milk progesterone concentrations the day of AI and 21-24 days later. The frequency of NF-EEL has been reported to be between 25 and 45% in lactating Holstein cows (26,32,35,52), and it has increased from the 1980s (22).Age/parity, uterine health (nulliparous heifers vs. postpartum cows), and metabolic and endocrine environment are factors that can explain differences in reproductive efficiency. Maternal metabolism is known to influence fertility. Milk production, body condition score (BCS), postpartum BCS variations, negative energy balance (NEB), and quantity and quality of dietary protein supply are related to pregnancy rate (reviews Refs. 15,40,45,65,73,76). This effect might be explained partly by the clearance of progesterone in highproducing dairy cows (22) and by poor oocyte quality (43), which impair fertilization ability and early e...

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Objective The adipogenic PPARG-encoded PPARγ nuclear receptor also display essential placental functions. We evaluated metabolic, reproductive and perinatal features of patients with PPARG-related lipodystrophy. Methods Current and retrospective data were collected in patients referred to a National Rare Diseases Reference Centre. Results 26 patients from 15 unrelated families were studied (18 women, median age 43 years). They carried monoallelic PPARG variants except a homozygous patient with congenital generalized lipodystrophy. Among heterozygous patients aged 16 or more (n = 24), 92% had diabetes, 96% partial lipodystrophy (median age at diagnosis 24 and 37 years, respectively), 78% hypertriglyceridemia, 71% liver steatosis and 58% hypertension. Mean BMI was 26 ± 5.0 kg/m2. Women (n = 16) were frequently affected by acute pancreatitis (n = 6) and/or polycystic ovary syndrome (n = 12). Eleven women obtained one or several pregnancies, all complicated by diabetes (n = 8), hypertension (n = 4) and/or hypertriglyceridemia (n = 10). We analysed perinatal data of patients according to the presence (n = 8) or absence (n = 9) of maternal dysmetabolic environment. The median gestational age at birth was low in both groups (37 and 36 weeks of amenorrhea, respectively). As expected, birth weight was higher in patients exposed to a fetal dysmetabolic environment of maternal origin. In contrast, 85.7% of non-exposed patients, in whom the variant is, or is very likely to be, paternally-inherited, were small for gestational age. Conclusions Lipodystrophy-related PPARG variants induce early metabolic complications. Our results suggest that placental expression of PPARG pathogenic variants carried by affected fetuses could impair prenatal growth and parturition. This justifies careful pregnancy monitoring in affected families.