Associations of Diabetes-related and Health-related Quality of Life With Glycemic Levels in Adolescents With Type 1 Diabetes Preparing to Transition to Adult Care.

OBJECTIVES: As adolescents with type 1 diabetes (T1D) progress to adulthood, they assume responsibility for diabetes self-management while dealing with competing life demands, decreasing parental support, and the transfer to adult care. Lower perceived quality of life (QOL) may hamper diabetes management, which is associated with suboptimal glycemic levels. Our objective was to determine associations of diabetes- and health-related QOL with glycemic management (glycated hemoglobin [A1C]) in adolescents with T1D before their transfer to adult care. METHODS: We conducted a cross-sectional analysis of baseline data from the Group Education Trial to Improve Transition (GET-IT- T1D) in adolescents with T1D (16 to 17 years of age). Participants completed validated questionnaires measuring diabetes-related QOL (PedsQL 3.2 Diabetes Module) and health-related QOL (PedsQL 4.0 Generic Core Scales). Associations of QOL Total and subscale scores with A1C were assessed using linear regression models adjusted for sex, diabetes duration, socioeconomic status, insulin pump use, and mental health comorbidity. RESULTS: One hundred fifty-three adolescents with T1D were included (mean age, 16.5 [standard deviation, 0.3] years). Diabetes-related QOL Total scores (adjusted ß=-0.04; 95% confidence interval [CI], -0.05 to -0.02) as well as subscale scores for Diabetes Symptoms (adjusted ß=-0.02; 95% CI, -0.04 to -0.00) and Diabetes Management (adjusted ß=-0.04; 95% CI, -0.05 to -0.02) were inversely associated with A1C. Health-related QOL Total scores were not associated with A1C, but Psychosocial Health subscale scores were (adjusted ß=-0.01; 95% CI, -0.03 to -0.00). CONCLUSION: Our results suggest that strategies focussing on diabetes-related QOL and psychosocial health may help prepare adolescents for the increasing responsibility of diabetes self-care.

Comparison of cattle derived from in vitro fertilization, multiple ovulation embryo transfer, and artificial insemination for milk production and fertility traits.

The use of assisted-reproduction technologies such as in vitro fertilization (IVF) is increasing, particularly in dairy cattle. The question of consequences in later life has not yet been directly addressed by studies on large animal populations. Studies on rodents and early data from humans and cattle suggest that in vitro manipulation of gametes and embryos could result in long-term alteration of metabolism, growth, and fertility. Our goal was to better describe these presumed consequences in the population of dairy cows produced by IVF in Québec (Canada) and to compare them to animals conceived by artificial insemination (AI) or multiple ovulation embryo transfer (MOET). To do so, we leveraged a large phenotypic database (2.5 million animals and 4.5 million lactations) from milk records in Québec aggregated by Lactanet (Sainte-Anne-de-Bellevue, QC, Canada) and spanning 2012 to 2019. We identified 304,163, 12,993, and 732 cows conceived by AI, MOET, and IVF, respectively, for a total of 317,888 Holstein animals from which we retrieved information for 576,448, 24,192, and 1,299 lactations (total = 601,939), respectively. Genetic energy-corrected milk yield (GECM) and Lifetime Performance Index (LPI) of the parents of cows were used to normalize for genetic potential across animals. When compared with the general Holstein population, MOET and IVF cows outperformed AI cows. However, when comparing those same MOET and IVF cows with only herdmates and accounting for their higher GECM in the models, we found no statistical difference between the conception methods for milk production across the first 3 lactations. We also found that the rate of Lifetime Performance Index improvement of the IVF population during the 2012 to 2019 period was less than the rate observed in the AI population. Fertility analysis revealed that MOET and IVF cows also scored 1 point lower than their parents on the daughter fertility index and had a longer interval from first service to conception, with an average of 35.52 d compared with 32.45 for MOET and 31.87 for AI animals. These results highlight the challenges of elite genetic improvement while attesting to the progress the industry has made in minimizing epigenetic disturbance during embryo production. Nonetheless, additional work is required to ensure that IVF animals can maintain their performance and fertility potential.

Gestational and health outcomes of dairy cows conceived by assisted reproductive technologies compared to artificial insemination.

Herd gestation and health management are key aspects of effective dairy farm operations and animal welfare improvement. Unfortunately, very little is known about the developmental divergences induced by assisted reproduction technologies (ART) and their consequences once the animal is mature. Indeed, the gestational and health outcomes of this subset of the Holstein population is yet to be characterized. In this study, the intergenerational impacts of ART conception were assessed by looking at the gestation and health outcomes of a large cohort of cows (n = 284,813) for which the conception methods were known. Our results showed that cows conceived by multiple ovulation embryo transfer (MOET) and in vitro fertilisation (IVF) displayed longer gestations: +0.37 ± 0.079 and +0.65 ± 0.21 day compared to cows conceived by artificial insemination (AI). Surprisingly, animals conceived by all methods experienced a similar 1-day decline in average gestation length from 2012 to 2019. Cows conceived by IVF were not more likely to experience stillbirths but were affected by common diseases such as ovarian cysts, mastitis, and uterine diseases in different proportions compared to cows conceived by other methods. This study provides new and unique information on ART animals regarding perinatal mortality and general health outcomes.

IGF2R, KCNQ1, PLAGL1, and SNRPN DNA methylation is completed in bovine by the early antral follicle stage.

Imprinted genes are inherited with different DNA methylation patterns depending on the maternal or paternal origin of the allele. In cattle (Bos taurus), abnormal methylation of these genes is linked to the large offspring syndrome, a neonatal overgrowth phenotype analogous to the human Beckwith-Wiedemann syndrome. We hypothesized that in bovine oocytes, some of the methylation patterns on maternally imprinted genes are acquired in the last phase of folliculogenesis. The pyrosequencing analysis of IGF2R, KCNQ1, PLAGL1, and SNRPN imprinted genes showed no clear progression of methylation in oocytes from follicles 1-2 mm (late pre antral/early antral) and up. Instead, these oocytes displayed complete methylation at the imprinted differentially methylated regions (>80%). Other mechanisms related to imprint maintenance should be investigated to explain the hypomethylation at IGF2R, KCNQ1, PLAGL1, and SNRPN maternally imprinted sites observed in some bovine embryos.

Specific imprinted genes demethylation in association with oocyte donor's age and culture conditions in bovine embryos assessed at day 7 and 12 post insemination.

The production of bovine embryos through in vitro maturation and fertilization is an important tool of the genomic revolution in dairy cattle. Gene expression analysis of these embryos revealed differences according to the culture conditions or oocyte donor's pubertal status compared to in vivo derived embryos. We hypothesized that some of the methylation patterns in oocytes are acquired in the last step of folliculogenesis and could be influenced by the environment created in the follicles containing these oocytes. These altered patterns may not be erased during the first week of embryonic development in culture or may be sensitive to the conditions during that time. To quantify the changes related to culture conditions, an in vivo control group consisting of embryos (Day 12 post fertilization for all groups) obtained from superovulated and artificially inseminated cows was compared to in vitro produced (IVP) embryos cultured with or without Fetal Bovine Serum (FBS). To measure the effect of the oocytes donor's age, we also compared a fourth group consisting of IVP embryos produced with oocytes collected following ovarian stimulation of pre-pubertal animals. Embryonic disk and trophoblast cells were processed separately and the methylation status of ten imprinted genes (H19, MEST, KCNQ1, SNRPN, PEG3, NNAT, GNASXL, IGF2R, PEG10, and PLAGL1) was assessed by pyrosequencing. Next, ten Day 7 blastocysts were produced following the same methodology as for the D12 embryos (four groups) to observe the most interesting genes (KCNQ1, SNRPN, IGF2R and PLAGL1) at an earlier developmental stage. For all samples, we observed overall lower methylation levels and greater variability in the three in vitro groups compared to the in vivo group. The individual embryo analysis indicated that some embryos were deviant from the others and some were not affected. We concluded that IGF2R, SNRPN, and PEG10 were particularly sensitive to culture conditions and the presence of FBS, while KCNQ1 and PLAGL1 were more affected in embryos derived from pre-pubertal donors. This work provides markers at the single imprinted control region (ICR) resolution to assess the culture environment required to minimize epigenetic perturbations in bovine embryos generated by assisted reproduction techniques, thus laying the groundwork for a better comprehension of the complex interplay between in vitro conditions and imprinted genes.

Expression of atresia biomarkers in granulosa cells after ovarian stimulation in heifers.

The use of younger gamete donors in dairy cattle genetic selection programs significantly accelerates genetic gains by decreasing the interval between generations. Ovarian stimulation (OS) and the practice of follicle-stimulating hormone (FSH) withdrawal, also known as coasting, are intensively used in pre-pubertal heifers without detrimental effects on subsequent reproductive performance but generally with lower embryo yields. However, recent data from embryo transfer programs showed similar embryo yields in younger and sexually mature animals but with a significant difference in the coasting period. The aim of the present study was to identify a set of granulosa cell biomarkers capable of distinguishing optimal follicle differentiation from late differentiation and atresia in order to assess the differences in coasting dynamics between pre- and post-pubertal donors. We integrated transcriptomic data sets from a public depository and used vote counting meta-analysis in order to elucidate the molecular changes occurring in granulosa cells during late follicle differentiation and atresia. The meta-analysis revealed the gene expression associated with follicle demise, and most importantly, identified potential biomarkers of that status in bovine granulosa cells. The comparison of the expression of six biomarkers between pre- and post-pubertal donors revealed that younger donors had more signs of atresia after the same period of coasting. We found different follicular dynamics following coasting in younger donors. It is possible that younger donors are less capable to sustain follicular survival most likely due to insufficient luteinizing hormone signaling. In summary, the pre-pubertal status influences follicular dynamics and reduces the oocyte developmental competence curve following OS and FSH withdrawal in heifers.