Puberty classifications in beef heifers are moderately to highly heritable and associated with candidate genes related to cyclicity and timing of puberty.

Introduction: Pubertal attainment is critical to reproductive longevity in heifers. Previously, four heifer pubertal classifications were identified according to attainment of blood plasma progesterone concentrations > 1 ng/ml: 1) Early; 2) Typical; 3) Start-Stop; and 4) Non-Cycling. Early and Typical heifers initiated and maintained cyclicity, Start-Stop started and then stopped cyclicity and Non-Cycling never initiated cyclicity. Start-Stop heifers segregated into Start-Stop-Discontinuous (SSD) or Start-Stop-Start (SSS), with SSD having similar phenotypes to Non-Cycling and SSS to Typical heifers. We hypothesized that these pubertal classifications are heritable, and loci associated with pubertal classifications could be identified by genome wide association studies (GWAS). Methods: Heifers (n = 532; 2017 - 2022) genotyped on the Illumina Bovine SNP50 v2 or GGP Bovine 100K SNP panels were used for variant component estimation and GWAS. Heritability was estimated using a univariate Bayesian animal model. Results: When considering pubertal classifications: Early, Typical, SSS, SSD, and Non-Cycling, pubertal class was moderately heritable (0.38 ± 0.08). However, when heifers who initiated and maintained cyclicity were compared to those that did not cycle (Early+Typical vs. SSD+Non-Cycling) heritability was greater (0.59 ± 0.19). A GWAS did not identify single nucleotide polymorphisms (SNPs) significantly associated with pubertal classifications, indicating puberty is a polygenic trait. A candidate gene approach was used, which fitted SNPs within or nearby a set of 71 candidate genes previously associated with puberty, PCOS, cyclicity, regulation of hormone secretion, signal transduction, and methylation. Eight genes/regions were associated with pubertal classifications, and twenty-two genes/regions were associated with whether puberty was attained during the trial. Additionally, whole genome sequencing (WGS) data on 33 heifers were aligned to the reference genome (ARS-UCD1.2) to identify variants in FSHR, a gene critical to pubertal attainment. Fisher's exact test determined if FSHR SNPs segregated by pubertal classification. Two FSHR SNPs that were not on the bovine SNP panel were selected for additional genotyping and analysis, and one was associated with pubertal classifications and whether they cycled during the trial. Discussion: In summary, these pubertal classifications are moderately to highly heritable and polygenic. Consequently, genomic tools to inform selection/management of replacement heifers would be useful if informed by SNPs associated with cyclicity and early pubertal attainment.

Interleukin-6 supplementation improves bovine conceptus elongation and transcriptomic indicators of developmental competence†.

A high incidence of pregnancy failures occurs in cattle during the second week of pregnancy as blastocysts transition into an elongated conceptus. This work explored whether interleukin-6 supplementation during in vitro embryo production would improve subsequent conceptus development. Bovine embryos were treated with 0 or 100 ng/mL recombinant bovine interleukin-6 beginning on day 5 post-fertilization. At day 7.5 post-fertilization, blastocysts were transferred into estrus synchronized beef cows (n = 5 recipients/treatment, 10 embryos/recipient). Seven days after transfer (day 14.5), cows were euthanized to harvest reproductive tracts and collect conceptuses. Individual conceptus lengths and stages were recorded before processing for RNA sequencing. Increases in conceptus recovery, length, and the proportion of tubular and filamentous conceptuses were detected in conceptuses derived from interleukin-6-treated embryos. The interleukin-6 treatment generated 591 differentially expressed genes in conceptuses (n = 9-10/treatment). Gene ontology enrichment analyses revealed changes in transcriptional regulation, DNA-binding, and antiviral actions. Only a few differentially expressed genes were associated with extraembryonic development, but several differentially expressed genes were associated with embryonic regulation of transcription, mesoderm and ectoderm development, organogenesis, limb formation, and somatogenesis. To conclude, this work provides evidence that interleukin-6 treatment before embryo transfer promotes pre-implantation conceptus development and gene expression in ways that resemble the generation of a robust conceptus containing favorable abilities to survive this critical period of pregnancy.

An Overview of Reactive Oxygen Species Damage Occurring during In Vitro Bovine Oocyte and Embryo Development and the Efficacy of Antioxidant Use to Limit These Adverse Effects.

The in vitro production (IVP) of bovine embryos has gained popularity worldwide and in recent years and its use for producing embryos from genetically elite heifers and cows has surpassed the use of conventional superovulation-based embryo production schemes. There are, however, several issues with the IVP of embryos that remain unresolved. One limitation of special concern is the low efficiency of the IVP of embryos. Exposure to reactive oxygen species (ROS) is one reason why the production of embryos with IVP is diminished. These highly reactive molecules are generated in small amounts through normal cellular metabolism, but their abundances increase in embryo culture because of oocyte and embryo exposure to temperature fluctuations, light exposure, pH changes, atmospheric oxygen tension, suboptimal culture media formulations, and cryopreservation. When uncontrolled, ROS produce detrimental effects on the structure and function of genomic and mitochondrial DNA, alter DNA methylation, increase lipid membrane damage, and modify protein activity. Several intrinsic enzymatic pathways control ROS abundance and damage, and antioxidants react with and reduce the reactive potential of ROS. This review will focus on exploring the efficiency of supplementing several of these antioxidant molecules on oocyte maturation, sperm viability, fertilization, and embryo culture.

Fibroblast Growth Factor 21 Has a Diverse Role in Energetic and Reproductive Physiological Functions of Female Beef Cattle.

Fibroblast growth factor 21 (FGF21) has been identified in multiple mammalian species as a molecular marker of energy metabolism while also providing negative feedback to the gonads. However, the role of FGF21 in regulating the energetic and reproductive physiology of beef heifers and cows has yet to be characterized. Herein, we investigated the temporal concentrations of FGF21 in female beef cattle from the prepubertal period to early lactation. Circulating concentrations of FGF21, non-esterified fatty acids, plasma urea nitrogen, glucose, and progesterone were assessed. Ultrasonography was employed to determine the onset of puberty and resumption of postpartum ovarian cyclicity as well as to measure backfat thickness. Finally, cows and calves underwent the weigh-suckle-weigh technique to estimate rate of milk production. We have revealed that FGF21 has an expansive role in the physiology of female beef cattle, including pubertal onset, adaptation to nutritional transition, rate of body weight gain, circulating markers of metabolism, and rate of milk production. In conclusion, FGF21 plays a role in physiological functions in beef cattle that can be applied to advance the understanding of basic scientific processes governing the nutritional regulation of reproductive function but also provides a novel means for beef cattle producers to select parameters of financial interest.

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum.

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptor-mediated activation of PINK-Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility.

Influences of Supplementing Selective Members of the Interleukin-6 Cytokine Family on Bovine Oocyte Competency.

This work explored whether supplementing selective members of the interleukin-6 (IL6) cytokine family during in vitro bovine oocyte maturation affects maturation success, cumulus-oocyte complex (COC) gene expression, fertilization success, and embryo development potential. Human recombinant proteins for IL6, IL11, and leukemia inhibitory factor (LIF) were supplemented to COCs during the maturation period, then fertilization and embryo culture commenced without further cytokine supplementation. The first study determined that none of these cytokines influenced the rate that oocytes achieved arrest at meiosis II. The second study identified that LIF and IL11 supplementation increases AREG transcript abundance. Supplementation with IL6 supplementation did not affect AREG abundance but reduced HAS2 transcript abundance. Several other transcriptional markers of oocyte competency were not affected by any of the cytokines. The third study determined that supplementing these cytokines during maturation did not influence fertilization success, but either LIF or IL11 supplementation increased blastocyst development. No effect of IL6 supplementation on subsequent blastocyst development was detected. The fourth experiment explored whether each cytokine treatment affects the post-thaw survivability of cryopreserved IVP blastocysts. None of the cytokines supplemented during oocyte maturation produced any positive effects on post-thaw blastocyst re-expansion and hatching. In conclusion, these outcomes implicate IL11 and LIF as potentially useful supplements for improving bovine oocyte competency.

Bioactive supplements influencing bovine in vitro embryo development.

Ovum pickup and in vitro production (IVP) of bovine embryos are replacing traditional multiple ovulation embryo transfer (MOET) as the primary means for generating transferable embryos from genetically elite sires and dams. However, inefficiencies in the IVP process limit the opportunities to produce large numbers of transferable embryos. Also, the post-transfer competency of IVP embryos is inferior to embryos produced by artificial insemination or MOET. Numerous maternal, paternal, embryonic, and culture-related factors can have adverse effects on IVP success. This review will explore the various efforts made on describing how IVP embryo development and post-transfer competency may be improved by supplementing hormones, growth factors, cytokines, steroids and other bioactive factors found in the oviduct and uterus during early pregnancy. More than 40 of these factors, collectively termed as embryokines, are reviewed here. Several embryokines contain abilities to promote embryo development, including improving embryo survivability, improving blastomere cell numbers, and altering the distribution of blastomere cell types in blastocysts. A select few embryokines also can benefit pregnancy retention after IVP embryo transfer and improve neonatal calf health and performance, although very few embryokine-supplemented embryo transfer studies have been completed. Also, supplementing several embryokines at the same time holds promise for improving IVP embryo development and competency. However, more work is needed to explore the post-transfer consequences of adding these putative embryokines for any adverse outcomes, such as large offspring syndrome and poor postnatal health, and to specify the specific embryokine combinations that will best represent the ideal conditions found in the oviduct and uterus.

Ovum pickup and in-vitro production (IVP) of bovine embryos have quickly become commercial options for generating large quantities of transferable bovine embryos from genetically elite sires and dams. However, 2 limitations in this process still exist. First, the percentage of eggs/oocytes that become fertilized and produce transferable embryos remains low. Second, IVP embryos that are transferred to recipients are less able to maintain a viable pregnancy than embryo produced by other means. Various maternal, paternal, embryonic, and culture-related factors will influence IVP success. This review describes how both IVP embryo development and post-transfer embryo competency may be improved by supplementing hormones, growth factors, cytokines, steroids, and other bioactive factors found in the oviduct and uterus during early pregnancy. These factors are collectively termed as embryokines. Several embryokines will promote IVP embryo development, but only a few of these embryokines have been tested for their ability to improve post-embryo transfer pregnancy retention. More work is needed to explore the post-transfer consequences of adding embryokines. However, with that being said, all indications are that we are on the right track with identifying one and likely several embryokines that will improve IVP embryo development and post-transfer pregnancy retention in cattle.

Utilizing in-vivo feedback for caregiver training of pediatric feeding protocols.

Researchers have used multicomponent behavioral skills training packages including written and verbal instructions, modeling, rehearsal, and feedback when teaching caregivers to implement pediatric feeding treatment protocols (e.g., Anderson & McMillan, 2001; Seiverling et al., 2012). Some investigators have shown that fewer behavioral skills training components may be necessary for effective training (e.g., Mueller et al., 2003; Pangborn et al., 2013). We examined the use of in-vivo feedback following written instructions to train caregivers to implement pediatric feeding treatment protocols using a multiple baseline design across 3 caregiver dyads. Correct implementation of the feeding treatment procedures was low during baseline (written instructions only), increased with only the addition of in-vivo feedback, and remained high during follow-up sessions for all caregivers. Results are discussed in terms of clinical implications and caregiver satisfaction.

Neonatal weight loss and gain patterns in caesarean section born infants: integrative systematic review.

There is evidence that caesarean section delivery can impact on neonatal weight loss and weight gain patterns in the first 5 days of life. We conducted an integrative systematic review to examine the association of mode of delivery on early neonatal weight loss. Pubmed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpta Medica dataBASE, and Medical Literature Analysis and Retrieval System Online were searched for relevant papers published before June 2019. Reference lists from the relevant papers were then backwards and forwards searched. As neonatal weight loss was reported in different formats, a meta-analysis could not be carried out. Most studies did not distinguish between elective and emergency caesarean sections or instrumental and nonassisted vaginal deliveries. Seven papers were included. All papers except one found that caesarean section was associated with higher weight loss in the early days of life. Two papers presented data from studies on babies followed up to 1 month. One study found that on day 25, babies born by caesarean section had significantly higher weight gain than those born vaginally, while another found that by day 28, babies born vaginally gained more weight per day (11.9 g/kg/day) than those born by caesarean section (10.9 g/kg/day; p = .02). Overall, infants born by caesarean section lost more weight than those born vaginally, but due to the small number of studies included, more are needed to look at this difference and why it may occur. This discrepancy in weight between the two groups may be corrected over time, but future studies will need larger sample sizes and longer follow-up periods to examine this.

Where is the family in global mental health?

This article comments on the article in the current issue by J. E. Patterson et al (see record 2018-27937-001) regarding families' role in global mental health. In the world's low- and middle-income countries, a person's identity is often located more within the family, clan, or tribe than the individual. The authors add to the discussion and call for family-centered stepped delivery of health care. The family should move to the forefront of global mental health clinical research, mental health policy, and human rights advocacy. (PsycINFO Database Record

Computer-based screening of veterans for metabolic syndrome.

BACKGROUND: The worldwide obesity epidemic has focused attention on the prevalence of the metabolic syndrome, which is greater than previously believed. However, estimates of its overall prevalence vary widely. We wished to ascertain the prevalence of metabolic syndrome in the Veteran Affairs Northern California Health Care System (VANCHCS). METHODS: We used the VA computerized clinical database and modified Adult Treatment Panel III (ATP III) criteria of fasting blood glucose (FBG) >or=110 mg/dL, blood pressure >or=130/>or=85, triglyceride >or=150 mg/dL, high-density lipoprotein cholesterol (HDL-C) <40 mg/dL (men) or <50 mg/dL (women), but body mass index (BMI) >or=30 in lieu of waist circumference >102 cm (40 inches) for men and 88 cm (35 inches) for women. We also accepted current pharmacotherapy for diabetes as qualifying for elevated fasting blood sugar (FBS); current therapy with niacin, gemfibrozil, or fenofibrate for elevated triglyceride concentrations; and recent use of multiple International Classification of Diseases, 9(th) Revision (ICD-9) codes for hypertension for elevated blood pressure. RESULTS: We examined all clinical records for veterans registered in VANCHCS who filled any prescription between July 1, 2004, and June 30, 2005 (n = 51,026). Their average age was 63 years; 93% were male. In all 25% (n = 13,010) were diagnosed as having metabolic syndrome by meeting at least 3 of the above 5 criteria. Because only 60% (n = 30,727) of the population had data for 3 or more criteria, the actual percent with metabolic syndrome is probably substantially higher. CONCLUSIONS: Over one quarter of veterans in the VANCHCS may have metabolic syndrome based on our modified ATP III criteria. We urge screening more veterans with fasting laboratory testing. Computerized screening of a large clinical database can provide an effective strategy to aid clinicians in identifying more patients at risk for cardiovascular disease.