Sex-specific programming effects of parental obesity in pre-implantation embryonic development_Microarray data on blastocyst transcriptomes

Obesity is a global rising problem with epidemiological dimension. Obese parents can have programming effects on their offspring leading to obesity and associated diseases in later life. This constitutes a vicious circle. Epidemiological data and studies in rodents demonstrated differential programming effects in male and female offspring, but the timing of their developmental origin is not known. This study investigated if sex-specific programming effects of parental obesity can already be detected in the pre-implantation period. Diet induced obese male or female mice were mated with normal-weight partners and blastocysts were recovered. Gene expression profiling revealed sex-specific responses of the blastocyst transcriptome to maternal and paternal obesity. The changes in the transcriptome of male blastocysts were more pronounced than those of female blastocysts, with a stronger impact of paternal than of maternal obesity. The sperm of obese mice revealed an increased abundance of several miRNAs compared to lean mice. Our study indicates that sex-specific programming effects of parental obesity already start in the pre‑implantation period and reveals specific alterations of the sperm miRNA profile as mechanistic link to programming effects of paternal obesity. We used microarrays to analyze the transcriptomes of sex-sorted blastocysts of mice, with one parent (either mother or father) being obese at the time of conception and compared it to the transcriptome of blasocysts of peri-conceptionally lean parents. NMRI mice (RjHan:NMRI) were purchased from Janvier (Le Genest St Isle, France). For a period of nine weeks, cohorts of three-week-old mice were fed a modified D12492 high-fat, high-calorie diet (HFD) (E15741-34; ssniff, Soest, Germany), or received a control diet to D12492 (CD) (ssniff). At the age of 12 weeks mice were mated and at day 3.5 post coitum, blastocysts were isolated. The sex of the blastocysts was determined and the transcriptome of a pool of three sex-matched blastocysts was analyzed using microassrays. In total, we performed 24 microarrays. Of each parental pair (obese mother/lean father, lean mother/obese father, lean mother/lean father as controls), we investigated the the transcriptome of four male and four female blastocyst pools, respectively.