SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Milan Shipka – AK – Administrator Sean Limesand - AZ Anna Denicol – CA – Member-at-large Russ Anthony – CO Thomas Hansen - CO Kristen Govoni – CT John Hall – ID - Chair Phil Cardoso – IL David Grieger - KS Caleb Lemley - MS Andrea Cupp – NE Ryan Ashley – NM Jennifer Herdandez-Gifford - NM Michelle Kutzler - OR Wansheng Liu – PA Nathan Long - SC Ky Pohler – TX John Stevens - UT Brenda Alexander – WY

Accomplishments

Summary of accomplishments

During the 2019-2020 period, research projects developed by members of W3112 resulted in the training of dozens of undergraduate and graduate students at the M.S. and Ph.D. levels. At least 8 M.S. theses and 3 Ph.D. dissertations resulted from this work. Members of the W3112 also gave several invited presentations to share their research with national and international audiences. Due to the COVID-19 pandemic, many annual conferences had to be postponed, resulting in postponement of some presentations to 2021.

 

Research findings during the 2019-2020 period include:

  1. Placental insufficiency causes intrauterine growth restriction (IUGR) and disrupts fetal metabolism including adipogenesis, resulting in alterations in adipocyte number, size, and function.
  2. PPAR signaling is enhanced in adipose tissue of the PI-IUGR fetus.
  3. Perirenal adipose tissue exhibited greater hyperplasia and had higher expression of genes involved in cellular differentiation and fatty acid transport, which explains the propensity for early adiposity in offspring born with IUGR.
  4. Detection of MBP in the ovary of treated mice provides further evidence that oral dosing with DBP results in direct effects on the ovary.
  5. Preterm lambs and growth-restricted lamps demonstrate a significant risk of several disorders in adult life. Identifying these mechanisms are important from both domestic animals’ perspective and human health.
  6. Mid-gestational nutrient restriction and subsequent re-alimentation altered distinct metabolic amino acid, carbohydrate, and lipid pathways, potentially altering postnatal growth.
  7. Feeding rumen-protected lysine (RPL) around parturition results in modulation of genes involved in inflammatory and immune responses.
  8. Improvement in the uterine immunity resulted in maintaining a proper inflammatory response, decreasing in PMN counting and increasing anti-inflammatory cytokine IL10 by the fourth week postpartum, which indicates the resolution of the inflammatory process associated with clearance of pathogens and uterine involution.
  9. Cows that received RPL were less likely to develop purulent vaginal discharge.
  10. A stimulus to cell proliferation was evident as a response to RPL through the trend to increased number of uterine glandular epithelial cells.
  11. There was no effect of feeding RPL on the follicle size at the time of ovulation, but a lesser variation in growth rate of the dominant follicle was evident.
  12. Overall, feeding lysine throughout the transition period proved to be beneficial to the uterine immune function of the cow.
  13. The bovine endometrium stores glycogen in a reproductive-cycle dependent manner.
  14. Periodic acid-Schiff staining (PAS) staining indicated that glycogen was primarily stored in the glandular epithelial cells and this glycogen peaked on Day 1 of the reproductive cycle.
  15. Hexokinase was highly expressed in the glandular epithelial on both Day 1 and Day 11 of the cycle.
  16. The peak glycogen content on Day 1 of the reproductive cycle was due to increased expression of glycogen synthase and decreased levels of phospho-glycogen synthase.
  17. The glandular epithelia also expressed high levels of glucose-6-phosphatase, indicating that the epithelial cells can dephosphorylate glucose-6-phosphate liberated from glycogen.
  18. We observed PAS-positive material in the glandular lumen, suggesting that intact glycogen might be secreted into the uterine lumen. These results suggest that endometrial glycogen stores may contribute to subfertility in dairy cows.
  19. Concurrent disruptions in steroidogenic, immunological, and metabolic markers occur in cows diagnosed with cystic ovarian follicles (COF) and the pattern of dysregulation varies according to the number of days postpartum.
  20. Disturbances in cows diagnosed with COF at early postpartum (< 35 days in milk) were limited to steroidogenesis and metabolic markers, while COF-M/L cows (mid-late lactation; ≥ 118 days in milk) had steroidogenic, immunological and metabolic marker disorders.
  21. Our study provides evidence that the characterization of mechanisms associated with COF development in early and mid-late lactation needs to be further investigated to develop therapies that can mitigate the negative impact of COF in dairy cows with a distinct pathogenesis.
  22. Preliminary work indicates that melatonin supplementation increased testicular artery blood flow in bulls.
  23. The bovine vaginal microbiome is diverse, and no differences were found in the vaginal bacterial community profiles of heifers with different pregnancy status or endogenous concentrations of estradiol or progesterone.
  24. Although maternal nutrient restriction did not alter the diversity of the vaginal microbiota; dietary melatonin supplementation during pregnancy altered the beta diversity of the vaginal microbiota resulting in an environment that facilitates growth of aerobic bacteria.
  25. Parthenogenetic embryos have different secretion patterns and products compared to normal IVF embryos. Successful pregnancies sired by high fertility bulls with low late embryonic/fetal pregnancy loss have increased concentration of PAG at day 30 of gestation compared to low fertility sires. In addition, those sires have differences in genomic PAG markers.
  26. Cytokine and Bacteriome of postpartum cows through a synchronization protocol indicates a shift in bacterial communities in the uterus to decrease the diversity that may be important for pregnancy development.
  27. CXCL12/CXCR4 signaling during placental development serves as an important upstream regulator of placental vascularization possibly ensuring appropriate placental development throughout gestation. We propose the CXCL12-CXCR4 chemokine axis governs placental homeostasis by serving as a critical upstream mediator of vascularization and cell viability and, if this signaling axis is compromised, impaired placental development transpires.
  28. Disruption of normal CXCL12-mediated signaling during early placentation induces enduring placental effects manifesting later in gestation with several observed outcomes mirroring those of placental dysfunction, suggesting an imbalance in CXCL12-mediated signaling may be causative.
  29. Identification of environmental factors that affect puberty may allow for better management of these heifers to attain puberty in diverse weather patterns or drought. It may also allow for us to determine how environment affects puberty (mechanisms) or heifer genetics that is more redisposed to impact of environment.
  30. If elevated AMH at critical periods during pubertal development causes delayed puberty, we may be able to identify these individuals through genetic variants or altered AMH during puberty. This may inform beef producers of the females that would have longer reproductive lifespan.
  31. Understanding the pro-inflammatory and anti-inflammatory lipids that are elevated in follicular fluid or plasma of females where ovulation is induced may allow for the development of markers to detect ovulation or anovulation in females.
  32. Heifers classified as Non-Cycling (delayed puberty) had greater concentrations of TNFa when compared to heifers classified as Typical (normal puberty attainment) suggesting that increased inflammation may impact heifers to cause delayed puberty.

Impacts

  1. Understanding how phthalates impact retinoid acid signaling can facilitate the management of infertility caused by environmental contaminants.
  2. Understanding the molecular mechanism of cerebral autoregulation will have far-reaching usefulness. It will help determine the factors involved in fetal brain maturation.
  3. The finding that FSH plays a role in preantral follicle development has a potential impact on the use of the hormone in cattle ovarian stimulation protocols. It will be critical to test whether FSH could be used strategically to stimulate preanral follicles and improve performance of oocyte and embryo donors.
  4. Holstein cows carrying the slick gene could represent a tremendous advantage to the dairy industry if their production and reproduction is less compromised by heat stress.
  5. The economic analysis of the use of TAI versus NS programs should be a useful tool for beef producers in CA and other states to make well-informed management decisions.
  6. Development of a diagnostic for pregnancy status early during pregnancy would have tremendous economic benefit to producers raising ruminants.
  7. Discovery of genetic markers for embryo quality, elongation and survivability may lead to genetic selection of more fertile cattle.
  8. Validation of a panel of SNP associated with pregnancy success may help with development of screening tools to select cattle for improved reproduction.
  9. Development of lentiviral-mediated methods to target the expression of individual genes within the ruminant placenta provides the opportunity to examine cause and-effect relationships during pregnancy.
  10. CSH deficiencies, even in the absence of IUGR impacts uterine blood flow and fetal liver glucose utilization, which highlights that altered fetal development/metabolism can occur in the absence of effects on birthweight.
  11. An inverse relationship between fetal concentrations of glucagon and maternal concentrations of CSH is emerging from our work, implicating these two hormones as having significant relationships controlling both maternal and fetal environments during gestation.
  12. Alterations in leptin and ghrelin in ewes during gestation may disrupt critical metabolic adaptations that may contribute to suboptimal offspring growth and development.
  13. Altered nutrient exposure under production conditions may provide a model for further investigation of mechanisms of nutrient flow and lifetime impacts of standard production methods on reproduction and growth.
  14. Information about sperm storage could be used to lengthen sperm lifespan and allow less synchrony between insemination and ovulation.
  15. Potential biomarkers of summer heat stress may identify males with reduced fertility.
  16. Advancements of beef bull fertility, as well as early evaluation of artificial insemination sires, would have a beneficial impact on beef production.
  17. Elevated AMH during puberty may be used as an indicator of delayed puberty females.
  18. Systemic inflammation can be a contributor to delayed puberty.
  19. Environment can affect heifer pubertal attainment and that combined with genetic variants may determine heifers predisposed to adverse weather patterns or heat/cold stress.
  20. Pro-inflammatory or anti-inflammatory lipids maybe used as markers of ovulation or anovulation in beef cows.
  21. Intrauterine CXCL12-CXCR4 signaling governs endometrial and systemic inflammation important for placental development and disruption of this axis may have detrimental impacts on offspring and maternal health.
  22. Our sheep model of disrupted CXCL12-CXCR4 signaling at the fetal-maternal interface may prove to be a useful model to study placental dysfunction and other pregnancy disorders like preeclampsia.
  23. Accelerometers can accurately provide changes in activity detected by indicating timing of partition, allowing for increased producer monitoring.
  24. Based upon our research using a lower dose (1.5 mL) of PG-600 in sheep instead of the reviously published dose (5 mL), we have improved ewe pregnancy rates both during the breeding season and outside of the breeding season. This is also beneficial to sheep producers as the availability of PG-600 is limited, so the reduced dose allows producers to treat three times as many ewes without a drop in efficacy.
  25. Sequencing and annotation of the ovine and bovine Y chromosome are of significance for our understanding of Y-linked genes in male health, spermatogenesis, and fertility/infertility.
  26. Knowledge gained from the study of the PRAME/PRAMEY gene family will improve our understanding of the molecular mechanisms underlying spermatogenesis and fertilization, which in turn, will help us address issues related to male subfertility and infertility.
  27. PRAMEY may be used as a biomarker for sperm quality and sperm function.
  28. Semen exosome and sperm-derived tsRNAs may be used as biomarkers for male fertility evaluation.
  29. PGE2 is decreased early in gestation in cows that have successful pregnancies.
  30. Poor maternal nutrition may alter offspring muscle development through genes involved in cell signaling, inflammation, and epigenetic regulation.
  31. The fundamental information about sperm storage could be used to lengthen sperm lifespan and allow less synchrony between insemination and ovulation.

Publications

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