Brief Summary of Minutes of Annual Meeting

Minutes pasted with participant informatio.

The following have been accomplished:

Identification of the impact that thermal stress has on ovarian signaling is resulting in a mechanistic map being developed, upon which strategies to ameliorate seasonal infertility can be based.

Determined influence of a physiological stressor, obesity, on the ovarian capacity to respond to a toxic environmental stress.

Identified molecular proteins within the oocyte that contribute to viability of the oocyte.

Characterization of ovarian connexin proteins 37 and 43 to understand communication between somatic cells and the female gamete.

We have cultured ovarian oocytes to investigate intra-oocyte mechanisms of heat stress induced infertility.

Identified ovarian proteomic effects of obesity.

Determined that the response of OVCAR8 cells to PGF2α and PMA are not as robust as the human granulosa tumor cell line, KGN. While protein kinase C may have a role in regulating CCN1 expression, the constitutively high expression of STAT3 may be inhibiting CCN1 in OVCAR8 cells.

Determined that LH and mediators of the protein kinase A pathway, forskolin and db-cAMP, generally had no effect on CCN1, VEGFA and FGF2 expression in day 4 and 8 luteal cells.

Investigated the effects of Ovsynch manipulation on intraovarian events and pregnancy in multiparous dairy cows.

Examined the effects of location of the presumptive ovulatory follicle relative to the regressing CL (ipsilateral vs. contralateral).

Determined that TGFα stimulates proliferation of bGCs from small antral follicles via a MAPK-mediated mechanism, but may be incapable of promoting their persistence in follicles during the process of follicular selection/dominance.

Determined that the transcription factor, NR5A2, facilitates progesterone production in luteal cells, is inhibited by PGF2A, and is regulated by at least three microRNA, miR-27b-3p, miR-432-5p and miR-369-3p.

Completed metabolomic analyses that suggested a role for lipid mediators during luteal development and early pregnancy, as regulators of steroidogenesis, immune cells, intracellular signaling, and cell death. Two lipids that have been overlooked in the CL but may be important regulators of luteal function are 15-KETE and 5-KETE.

Discovered that conceptus signals alter the proportions and functions of immune cells in the peripheral blood and the fetal-maternal interface resulting in increased expression of functions associated with immune tolerance during early pregnancy in cattle.

Determined that zinc depletion impairs germ cell nest breakdown and follicle activation suggesting.

Identified potentially novel signaling pathways involved in oocyte maturaiton and cumulus expansion.

Determined that GHR and IGFI SNPs had no significant effect on fertility.

The SNP in TNFα had significant effects on fertility; BB cows being most disadvantaged.

Neither IGFI nor TNFα SNPs had a linear effect on days to pregnancy. However, combining the effects of SNPs in TNFα + IGFI, cows carrying more favorable alleles (AA for each gene) had fewer DIM to pregnancy than cows having BB genotype for both genes (AAAA=112±8, BBBB=126±10; Linear effect P=0.019).

Using a new dataset with 84 multiparous lactating dairy cows, genotyping has been conducted on SNP’s in another candidate gene: Coenzyme Q9 (COQ9).

Determined that cumulus cell expansion and gene expression of in vitro matured oocytes differ based upon estradiol and progesterone concentrations in maturation media.  Subsequent in vitro embryo development to the blastocyst stage was not affected by those treatments applied during the maturation phase. 

Determined that the addition of progesterone to maturation media containing follicle fluid supports embryo development to the blastocyst stage, while the addition of estradiol (alone or in combination with progesterone) inhibits blastocyst development.

Determined that maternal obesity modifies a subset of important mediators of embryonic and extraembryonic development in ovine conceptuses. Maternal obesity also modifies uterine gene expression during early pregnancy in sheep.

Volatile fatty acids can be used to manipulate progesterone profiles in cattle.

Investigated Bos indicus and Bos taurus cattle and how they differ in their ability to produce viable offspring following nutrient restriction during early pregnancy.

Determined that the cytokine, interleukin-6, improves development of the inner cell mass (ICM) in bovine embryos by utilizing STAT3-dependent signals.

Supplementing in vitro-produced bovine embryos will selective uterine-derived bioactive factors can modify events of early pregnancy after embryo transfer.

Determined that epidural administration of GnRH to cattle causes ovulation, but does not shorten the time to ovulation or lessen the variability in time to ovulation. While previous studies indicated this may be a strategy to improve ovulatory response (occurrence and timing), the current studies conducted in beef cows and heifers did not prove this hypothesis.

We have characterized the physiology that produces the high ovulation rate in carriers of Trio, a bovine high fecundity allele that leads to overexpression of SMAD6 in granulosa cells. Multiple follicles are selected in Trio at a smaller size, but at a similar time after initiation of a follicular wave, and with similar changes in granulosa cell gene expression as single-ovulating, non-carrier sisters (increased LH receptor, aromatase, PAPPA).

Determined that trio carriers have similar primordial follicle numbers and circulating AMH as non-carriers but an elevation in circulating FSH near the time of deviation, likely a key contributor to the increased ovulation rate in Trio carriers.

Discovered that treatment with a GnRH antagonist (Acyline) suppresses LH pulses and blocks selection of a dominant follicle and follicle growth past 8.5 mm. Provision of hCG (LH activity) restores dominant follicle growth. Thus, growth of follicles prior to 8.5 mm is not dependent on LH pulses but selection of a dominant follicle and growth after 8.5 mm is dependent on LH pulses.

The follicle selection process can be categorized by the size of the subordinate follicle at the time of selection into four categories: Conventional, undersized, Co-dominance, or Switched dominance. In elevated circulating progesterone heifers primarily undergo undersized deviation, whereas conventional deviation occurs in low progesterone concentrations.

Determined that although circulating LH is decreased in high progesterone, provision of hCG does not increase conventional deviation but tended to decrease the subordinate follicle size at deviation. Thus, undersized deviation is not due to suppressed circulating LH.

We determined the patterns of prostaglandin F_2α (PGF) pulses using circulating PGF metabolite (PGFM) during luteolysis, early pregnancy (Day 18-21), and the second month of pregnancy. Luteolysis is associated with distinct PGFM pulses that are suppressed during early pregnancy but are present during later pregnancy. Apparently mechanisms maintaining the CL are different in early and later pregnancy.

We have determined the differentially expressed (DE) transcriptome (RNASeq) during early pregnancy compared to cows at a similar stage of non-pregnancy that have not been exposed to prostaglandin F_2α (PGF) pulses (60 upregulated and 27 downregulated DE genes). Most of the upregulated genes were related to interferon-stimulated pathways.

We have determined the DE transcriptome during early luteolysis (initial exposure to PGF pulses but no decrease in circulating P4; 173 DE genes) and later luteolysis (after exposure to PGF metabolite > 100 pg/mL; 4615 DE genes).

We have used the RNASeq data from all the different physiologic states to identify and compare stably transcribed genes for future use as house-keeping genes in the CL.

A cytobrush method was validated for sequential analysis of gene expression in the endometrium before, during, and after luteolysis in heifers with 2 or 3 follicular waves.

Discovered that endometrial mRNA for progesterone receptors and estradiol receptors 1 and 2 were greater on Day 8 and decreased thereafter similarly in heifers with two and three follicular waves. Oxytocin receptor mRNA increased earlier in two vs three-wave cycles (Day 14 vs 18) and the increase was associated with the onset of luteolysis. Thus, endometrial expression of mRNA for the steroid receptors did not explain the variability in timing of onset of luteolysis in heifers while the later onset of luteolysis in three-wave cycles was associated with later up-regulation of oxytocin receptor mRNA.

Using a physiologic model of the the proestrous period, it was found that the changes in endometrial area normally associated with estrus only occurred with both a decrease in circulating P4 and an increase in circulating estradiol.

Endometrial expression of the receptor for oxytocin increases on Day 18 in non-pregnant heifers, prior to luteolysis, and on Day 32 of pregnancy but is suppressed on Day 18 of pregnancy, probably by interferon-tau.

Determined that endometrial expression of interferon-stimulated genes (ISGs) were elevated in Day 18 pregnant heifers but were low on Day 18 in non-pregnant heifers or on Day 32 of pregnancy. 

Objective 3: Identify changes in genetics and reproductive management that lead to improved pregnancy rates in ruminants.

Determined that production of an accessory CL using GnRH or hCG decreases pregnancy loss in recipients of in vitro produced (IVP) embryos.  In one study (n = 552), heifers were treated with 2,000 IU of hCG or were not treated after either AI or at time of transfer of an IVP embryo. Treatment with hCG caused ovulation and increased circulating P4 in both groups but only decreased pregnancy loss in IVP recipients and not in heifers that received AI.

In another study (n = 1,562), heifers were treated on Day 5 with 200 ug GnRH or were not treated and received an IVP embryo on Day 7 (+ 1 d). Treatment with GnRH caused ovulation (83.9%), increased circulating P4, and decreased pregnancy loss between Day 33 and 60 of pregnancy.

Pregnancy loss between day 33 and 60 in recipient heifers with or without an accessory CL present on D33 in an IVP-ET program.

Determined that presence of an accessory CL at the D33 pregnancy diagnosis was associated with a dramatic reduction in pregnancy loss from D33 to D60 in recipients of Stage 7 (expanded blastocyst) embryos (11.6 vs 27.6%).  Thus, formation of an accessory CL using hCG or GnRH does not seem to alter pregnancy per embryo transfer at the Day 33 pregnancy diagnosis but decreases pregnancy loss between Day 33 and Day 60 in recipients of Stage 7 embryos.  

Cows were classified as Control or High A4 based on detection of A4 in culture medium from ovarian cortex.  Furthermore, monthly blood and fecal samples were collected from beef heifers (n=112/year) beginning at weaning (Oct 2017, 2018) until breeding or ovariectomy (June 2018, 2019).  In addition, a sample was collected from each heifer just prior to weaning.

Blood samples from Control or High A4 cows were assayed for progesterone (P4) and heifers were classified into one of four puberty groups: typical (control), early, start-stop, or noncycling. DNA will be collected from fecal samples and metagenomic (shotgun sequencing) analyses performed on Control (n=18) and High A4 (n=18) cows. 

We have collected DNA from 3 Control and 3 High A4 cows which were sequenced in 2018.  Additional samples (6 per experimental group) will be sequenced in 2019 and bioinformatics analyses initiated.  We are also collecting monthly fecal samples from heifers between weaning and breeding which are classified based on days of age a puberty attainment and continued cyclicity; typical (378 ± 2 days), early 317 ± 4 days), start-stop (265 ± 4 days but discontinued cyclicity), and noncycling (no progesterone > 1 ng/mL).

Two new studies were initiated this year to measure the effect of inflammation on theca cell steroidogenesis.

Cytokine arrays showed increased TNFα and IL-1β secreted from theca cells from High A4 compared to control cows. We are in the process of measuring the concentration of LPS in follicular fluid collected from High A4 and control cows.

We have initiated a study, to localize lipids including cholesterol to specific cell types in the ovary.  The technique, Mass-Spectrometry Imaging, can both localize and determine the relative amount of specific lipid species in granulosa and theca cells from High A4 and Control cows.

A population of cows with increased ovarian androstenedione (High A4; >40ng/mL) concentrations has been identified in the UNL physiology herd. Interestingly, circulating and follicular fluid pro-inflammatory cytokine composition is altered in High A4 cows suggesting chronic inflammation.

Estrous cycles of High A4 and Control cows were synchronized and stimulated for 3 days with FSH (210 IU) prior to ovariectomy. Theca cells were micro-dissected from follicles >7mm and immediately cultured in untreated medium for 120 minutes or LPS-containing medium (50ng/ml) for 15 to 120 minutes. Western blot analysis showed progressive LPS-dependent increases in MyD88 in theca cells from Control cows. However, MyD88 expression was progressively decreased in theca cells from High A4 cows. Cytokine antibody arrays showed significant increases in pro-inflammatory cytokine concentrations (TNFα, IL-1α, and IL-21) in untreated medium from High A4 compared to Control theca cells. When Control theca cells were treated with LPS, TNF, IL-1, and IL-21 were significantly increased in a time-dependent manner. 

Determined that LPS treatment of High A4 theca cells resulted in significantly decreased levels of cytokines. These results suggest insensitivity of High A4 theca cells to LPS-mediated inflammatory response which may be due to chronic in vivo LPS exposure. Previous studies show that LPS increases ovarian steroidogenesis suggesting that chronic exposure of theca cells to LPS may be a mechanism for androgen excess in High A4 cows.

A population of cows that have excess androstenedione (A4; High A4) in follicular fluid of dominant follicles and secreted from ovarian cortex media (30-fold>controls) has been identified. High A4 cows have similar theca molecular phenotypes to women with polycystic ovary syndrome (PCOS) including: irregular estrous cycles, increased inflammation, and reduced fertility. Because PCOS is identified at puberty, the manner heifers attain puberty was investigated.

Heifers were classified using progesterone (P4) concentrations ≥ 1ng/ml to initiate puberty and continued cyclicity: 1) Typical- 378±2 day of age (DOA) (n=279); 2) Early- 317±4 DOA (n=143); 3) Start-Stop- P4 ≥1ng/ml at 265±4 but discontinued cyclicity (n=91); 4) Non-Cycling heifers- no occurrence of P4 ≥ 1ng/ml during sampling period (n=98). Start-Stop and Non-Cycling heifers also had excess A4 secretion from ovarian cortex cultures similar to High A4 cows.

Determined that weaning weight (p=0.017) was reduced in Start-Stop heifers and yearling weights (p=0.0074) was reduced in Start-Stop and Non-Cycling compared to Typical/Early heifers. Non-cycling heifers had the greatest Antral Follicle Counts (p<0.0001) with reduced uterine horn diameter (p=0.0053) compared to Typical (Control, p<0.0001) heifers.

Discovered that there was a lower proportion of Start-Stop and Non-Cycling heifers with a reproductive tract score of 5 compared with Typical/Early heifers, and less response to prostaglandin synchronization causing reduced calving in the first 21 days of the breeding season in the Non-cycling group.

Interestingly, heifers in the Start-Stop group that do not regain cyclicity have similar growth and reproductive traits as the Non-cycling heifers. Taken together, reduced growth and maturation observed in the Start-Stop and Non-Cycling heifers is initiated early in development and continues to adversely affect timing of reproductive maturity and longevity in these heifers.  

Determined that there was a tendency (P ≤ 0.09) for increased 17-OH progesterone and 11-deoxycortisol and fibrosis in Non-Cycling heifers. Cytokines CCL5, decorin, and IL-10 were also greater (P ≤ 0.05) in Unstimulated Non-cycling heifers with a tendency (P ≤ 0.09) for increased IFNβ, IL-1β, IL-17, CCL4, and IL-36Ra.

Determined that FSH-stimulation in Non-cycling heifers tended to reduce fibrosis, decorin, IFNβ, IL-1β, and CCL5 (P ≤ 0.03) to the level of the Unstimulated Typical (Control) heifers. In contrast, TNFα was increased (P = 0.05) in FSH-stimulated Non-Cycling heifers compared to other groups. Taken together, these results indicate that FSH-stimulation may restore the ovarian microenvironment of Non-cycling (High A4) heifers and reduce inflammation which may be a cause of follicle arrest.

We conducted a GWAS using 150,000 SNP markers (Geneseek GenomicProfiler Bovine 150K) genotyped in 200 individuals. As a result, we have identified 70 genes within 25 kb of genetic variants significantly (p<0.01) associated with the High A4 phenotype. Additionally, whole-genome sequence of 15 individuals (8 High A4, 7 Control) resulted in the identification of 4,600 variants with predicted high impact (via SNPEff). A total of ~17 million variants were observed in the sample.

High impact variants were identified in seven of the 70 genes identified in the initial GWAS.  We have assayed expression of CARNS1, CCR6, GPR31, ALKBH6, CLIP3, SREBP1a and SREBP1c via ddPCR in ovarian tissue, ovarian cortex, theca, and granulosa cells, in High A4 compared to controls cows.

In High A4 ovarian cortex, SREBP1c and CLIP3 were significantly upregulated compared to controls. There was a tendency for CARNS1 and CCR6 to be downregulated in High A4 granulosa cells. Three of the genes have a role with inflammatory regulation and one has a role in β-alanine metabolism of the High A4 phenotype. Understanding genetic variants can provide a potential tool for determining High A4 cows and removal from the herd.

Peer-reviewed journal articles reporting research from this project

Abuajamieh, M, Kvidera, SK, Mayorga, EJ, Kaiser, A, Lei, S, Seibert, JT, Horst, EA, Sanz Fernandez, MV, Ross, JW, Selsby, JT, Keating, AF, Rhoads, RP, Baumgard, LH 2018. The effect of recovery from heat stress on circulating bioenergetics and inflammatory biomarkers. Journal of Animal Science. 96(11):4599-4610.

Horst, EA, Kvidera, SK, Mayorga, EJ, Shouse, CS, Al-Qaisi, M, Dickson, MJ, Ydstie, J, Ramirez Ramirez, HA, Keating, AF, Dickson, DJ, Griswold, KE, Baumgard, LH. 2018. Effect of chromium on bioenergetics and leukocyte dynamics following immunoactivation in lactating Holstein cows. Journal of Dairy Science. 101(6):5515-5530.

Hristov, AN,  Degaetano, AT,  Rotz, CA, Hoberg, E, Skinner, RH, Felix, T, Li, H, Patterson, PH, Roth, G, Hall, M, Ott, TL, Baumgard, LH, Staniar, W, Hulet, RM, Dell, CJ, Brito, AF, Hollinger, DY. 2018. Climate change effects on livestock in the Northeast US and strategies for adaptation. Climatic Change 146 (1-2); pgs 33-45 doi.org/10.1007/s10584-017-2023-z

Hughes CK, Maalouf SW Liu W-S, Pate JL. 2019. Molecular profiling demonstrates modulation of immune cell function and matrix remodeling during luteal rescue. Biology of Reproduction, 2019, 0(0), 1–16 doi:10.1093/biolre/ioz037 Research Article Advance Access Publication Date: 27 March 2019

Hughes CK, Pate JL. 2019. Luteolysis and the Corpus Luteum of Pregnancy. In: The Ovary 3rd Edition, PCK Leung and EY Adashi, eds., Academic Press, Elsevier, pp. 270-295.  ISBN 978-0-12-813209-8

Ott, TL. 2019. Symposium Review: Immunological detection of the ruminant conceptus. Journal of Dairy Science 104(4): pgs 3766-3777 doi.org/10.3168/jds.2018-15668 

Pate JL, Hughes CK. 2018. Applications of large-scale molecular profiling techniques to the study of the corpus luteum. Anim. Reprod. 15:Suppl. 1, p. 791-804. DOI: 10.21451/1984-3143-AR2018-0038

Pate, JL. 2018. Luteolysis. In M. K. Skinner (Ed.), Encyclopedia of Reproduction. vol. 2, pp. 106–113. Academic Press: Elsevier. http://dx.doi.org/10.1016/B978-0-12-801238-3.64397-0

Silveira, PAS, WR Butler, SE LaCount, TR Overton, CC Barros, and A Schneider. 2019. Polymorphisms in the anti-oxidant paraoxonase-1 (PON1) gene associated with fertility of postpartum dairy cows. Theriogenology 125:302-309.

Bedford A, Beckett L, Hardin K, Dias NW, Davis T, Mercadante VR, Ealy AD and White RR. 2018. Propionate affects insulin signaling and progesterone profiles in dairy heifers. Sci. Rep. 8:17629.

Bonometti S, Menarim BC, Reinholt BM, Ealy AD and Johnson SE. 2019. Growth factor modulation of equine trophoblast mitosis and prostaglandin gene expression. J. Anim. Sci. 97:865-873. 

Ealy AD, Wooldridge LK and McCoski SR. 2019. Post-transfer consequences of in vitro-produced embryos in cattle. J. Anim. Sci. ePub 04/10/2019. 

Fontes PL, Oosthuizen N, Ciriaco FM, Sanford CD, Canal LB, Pohler KG, Henry DD, Mercadante VR, Timlin CL, Ealy AD, Johnson SE, DiLorenzo N and Lamb GC. 2019. Impact of fetal vs. maternal contributions of Bos indicus and Bos taurus genetics on embryonic and fetal development. J. Anim. Sci. 97:1645-1655.

McCoski SR, Poole RK, Vailes MT and Ealy AD. 2018. Maternal obesity alters the expression of embryonic regulatory transcripts in the preimplantation ovine conceptus. Repro. Biol. 18:198-201.

McCoski SR, Vailes MT, Owens, CE Cockrum RR and Ealy AD. 2018. Exposure to maternal obesity alters gene expression in the preimplantation ovine conceptus. BMC Genomics 19:737.

Vailes MT, McCoski SR, Wooldridge LK, Reese ST, Pohler KG, Roper DA, Mercadante VR and Ealy AD. 2019. Post-transfer outcomes in cultured bovine embryos supplemented with epidermal growth factor, fibroblast growth factor 2, and insulin-like growth factor 1. Theriogenology 124:1-8.

Wooldridge LK and Ealy AD. 2019. Interleukin-6 increases inner cell mass numbers in bovine embryos. BMC Dev. Biol. 19:2.

Zhang Z, Zhao LD, Johnson SE, Rhoads ML, Jiang H and Rhoads RP. 2019. Oxytocin is involved in steroid hormone-stimulated bovine satellite cell proliferation and differentiation in vitro. Domest. Anim. Endocrinol. 66:1-13.

Carvalho PD, Santos VG, Giordano JO, Wiltbank MC, Fricke PM. 2018. Development of fertility programs to achieve high 21-day pregnancy rates in high-producing dairy cows. Theriogenology 2018; 114:165-172.  10.1016/j.theriogenology. 03.037

Garcia-Guerra A, Canavessi AMO, Monteiro PLJ, Jr., Mezera MA, Sartori R, Kirkpatrick BW, Wiltbank MC. 2018. Trio, a novel bovine high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size. Biol Reprod 98:350-365.  10.1093/biolre/iox157

Garcia-Guerra A, Kamalludin MH, Kirkpatrick BW, Wiltbank MC. 2018. Trio a novel bovine high-fecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate. Biol Reprod 98:335-349.  10.1093/biolre/iox156

Garcia-Guerra A, Wiltbank MC, Battista SE, Kirkpatrick BW, Sartori R. 2018. Mechanisms regulating follicle selection in ruminants: lessons learned from multiple ovulation models. Animal Reproduction 15:660-679. 

Kamalludin MH, Garcia-Guerra A, Wiltbank MC, Kirkpatrick BW. 2018. Proteomic analysis of follicular fluid in carriers and non-carriers of the Trio allele for high ovulation rate in cattle. Reprod Fertil Dev  10.1071/RD17252

Kamalludin MH, Garcia-Guerra A, Wiltbank MC, Kirkpatrick BW. 2018. Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and noncarriers of a major gene for bovine ovulation rate. Biol Reprod 98:323-334.  10.1093/biolre/iox133

Melo LF, Monteiro PLJ, Jr., Nascimento AB, Drum JN, Spies C, Prata AB, Wiltbank MC, Sartori R. 2018. Follicular dynamics, circulating progesterone, and fertility in Holstein cows synchronized with reused intravaginal progesterone implants that were sanitized by autoclave or chemical disinfection. J Dairy Sci 101:3554-3567.  10.3168/jds.2017-13570

Melo LF, Monteiro PLJ, Jr., Oliveira LH, Guardieiro MM, Drum JN, Wiltbank MC, Sartori R. 2018. Circulating progesterone concentrations in nonlactating Holstein cows during reuse of intravaginal progesterone implants sanitized by autoclave or chemical disinfection. J Dairy Sci 101:3537-3544.  10.3168/jds.2017-13569

Ochoa JC, Penagaricano F, Baez GM, Melo LF, Motta JCL, Garcia-Guerra A, Meidan R, Pinheiro Ferreira JC, Sartori R, Wiltbank MC. 2018. Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2alpha. Biol Reprod 98:465-479.  10.1093/biolre/iox183

Silva EP, Wiltbank MC, Machado AB, Gambin LS, Dias MM, Chaiben MFC, Bernardi ML, Borges JBS. 2018. Optimizing timed AI protocols for Angus beef heifers: Comparison of induction of synchronized ovulation with estradiol cypionate or GnRH. Theriogenology 121:7-12.  10.1016/j.theriogenology.2018.07.019

Vasconcelos JLM, Pereira MHC, Wiltbank MC, Guida TG, Lopes Jr. FR, Sanches Jr. CP, Barbosa LFSP, Costa Jr. WM, Munhoz AK. 2018. Evolution of fixed-time AI in Brazil. Animal Reproduction 15: 940-951. 

Wiltbank MC, Mezera MA, Toledo MZ, Drum JN, Baez GM, Garcia-Guerra A, Sartori R. 2018. Physiological mechanisms involved in maintaining the corpus luteum during the first two months of pregnancy. Animal Reproduction 15:805-821.

Tenley SC, Spuri-Gomes R, Rosasco SL, Northrop EJ, Rich J, McNeel AK, Summers AF, Miles JR, Chase CC, Lents CA, Perry GA, Wood JR, Cupp AS, Cushman RA. 2018. Maternal Age Influences the Number of Primordial Follicles in the Ovaries of Yearling Angus Heifers, Animal Reproduction Science 200:105-112

McFee RM, Cupp AS, and Wood JR. 2018. Use of case-based or hands-on lab exercises with physiology lectures improves knowledge retention but veterinary medicine students prefer case-based activities, Adv Physiology Education, 42(2):182-191

Wood JR, and Cupp AS. 2018. Aromatization. In M. K. Skinner (Ed.), Encyclopedia of Reproduction. vol. 2, pp. 195–201. Academic Press: Elsevier. http://dx.doi.org/10.1016/B978-0-12-801238-3.64642-1

Ganesan, S, Dickson, MJ, Keating, AF. 2018. Pesticides. In M. K. Skinner (Ed.), Encyclopedia of Reproduction. vol. 2, pp. 724–730. Academic Press: Elsevier.

Clark, KL, Ganesan, S, Keating, AF. 2018. Impact of Toxicant Exposures on Ovarian Gap Junctions. Reproductive Toxicology. 81:140-146.

Bidne, KL, Dickson, MJ, Ross, JW, Baumgard, LH, Keating, AF. 2018. Disruption of female reproductive function by endotoxins. Reproduction. 155(4):R169-R181.

Conference papers and abstracts/presentations

Clark, KL, Talton, O, Ganesan, A, Schulz, LC, Keating AF. 2018. Lean maternal gestational diabetes mellitus impacts the ovarian proteome basally and in response to a stressor in later life. Society for the Study of Reproduction annual meeting, New Orleans.

Parrish, JJ, Keating, AF, Pate, JL, Pohler, KG, Wiltbank, MC, Ealy, AD. 2018. Changing paradigm in graduate education: Collaborative on-line approach in Reproduction. American Society of Animal Science annual meeting.

Piet S, Walker S, Tsang PCW.  2019. Expression and Regulation of Cysteine Rich 61-Connective Tissue Growth Factor-Nephroblastoma Overexpressed (CCN1) in Ovarian Adenocarcinoma (OVCAR8) Cells. 52nd Annual Meeting of the Society for the Study of Reproduction, San Jose, CA.

Wiltbank MC, Carvalho PD, Barletta RV, Fricke PM, Shaver RD. 2018. Relationships Among Changes in Body Condition Score and Reproductive Efficiency in Lactating Dairy Cows. 27th Tri-State Dairy Nutrition Conference 2018:121-138. 

Goulet M, Donahue J, Tsang PCW. 2019. Regulation of the Angiogenic Inducer, Cysteine Rich 61-Connective Tissue Growth Factor-Nephroblastoma Overexpressed 1 (CCN1), in Bovine Luteal Cells. 52nd Annual Meeting of the Society for the Study of Reproduction, San Jose, CA.

Lundberg, Jaskiewicz NJ, Townson DH. 2019. Stimulatory effects of Transforming Growth Factor-alpha in bovine granulosa cells of small antral follicles. Society for the Study of Reproduction Annual Meeting

Arbeithuber B, Stoler N, Higgins B, Hester JM, Diaz F, Nekrutenko A, Makova KD. 2018. Rare mitochondrial DNA variant analysis in single oocytes using duplex sequencing. 31st annual meeting of The Biology of Genomes. Cold Springs Harbor Laboratory.  Cold Springs Harbor, NY. May 8-12.

Baddela VS, Hughes CK and Pate JL. 2018. Let7 miRNA are abundant in the bovine corpus luteum and regulate cellular metabolic functions Society for the Study of Reproduction, New Orleans, LA

Butler WR, Schneider A, Silveira PAS, Townson DH, Tsang PCW, Dailey RA, Ott TL and Pate JL. 2018. Effects of polymorphisms in GHR, IGF-I and TNFα genes on fertility in lactating dairy cows. Amer Dairy Sci Association

Butler, W.R., Schneider., A., Silveira. P.A.S., Townson, D.H., Tsang, P.C.W., Dailey, R.A., Diaz FJ. 2018. Sufficient Dietary Zinc During the Preconception Period is Essential for Oocyte Competence.  Endocrine Society Annual Meeting, Chicago, IL. March 17-20.

Harper, MT, Oh, J, Melgar, A, Nedelkov, K, Räisänen, S, Chen, X, Martins, CMMR, Young, M, Ott,TL, Kniffen, DM, Fabin, R, Hristov, AN. 2018. Production effects of extruded soybean meal in early lactation cow diets. Journal of Dairy Science, 102 (Suppl 2) Abst: 510.

Hester JM and Diaz FJ. 2018. Growing Oocytes Need Zinc: Zinc Deficiency in the Preantral Ovarian Follicle.  Experimental Biology Meeting, San Diego CA.  *Endocrinology and metabolism section research recognition award.

Hughes CK, Maalouf SW Liu W-S, Pate JL. 2019. Molecular profiling demonstrates modulation of immune cell function and matrix remodeling during luteal rescue. Biology of Reproduction, 2019, 0(0), 1–16 doi:10.1093/biolre/ioz037 Research Article Advance Access Publication Date: 27 March 2019

Hughes CK, Rogus A, Inskeep EK and Pate. 2018. Functional transitions in the corpus luteum are associated with changes in NR5A2 abundance, which regulates luteal progesterone production. Proc. 10th Int Ruminant Reprod Symp, Foz do Iguacu, Brazil

Hughes CK, Wetzel LM, Bosviel R, Newman J and Pate JL. 2018. Luteal metabolomics suggests a role for lipid mediators as regulators of cell death, cell migration, and immune function. Society for the Study of Reproduction, New Orleans, LA

Lupicka M and Pate JL. 2018. Luteal Extracellular Vesicles Carry MicroRNA and Modulate Cytokine Secretion from Immune Cells. Society for the Study of Reproduction, New Orleans, LA

Melgar, A, Harper, MT, Oh, J, Giallongo, F, Fetter, ME, Ott, TL, Duval, S, Hristov, AN. 2018. Effects of 3-nitrooxypropanol on rumen fermentation, lactational performance, and onset of ovarian activity in dairy cows. Journal of Dairy Science, 102 (Suppl 2) Abst: 209.

Ott, TL, Pate, JL. 2018. Effects of polymorphisms in GHR, IGFI and TNFA genes on fertility in lactating dairy cows. Journal of Dairy Science, 102 (Suppl 2) Abst. T207

Ott, TL., 2018. Immune recognition of the periattachment conceptus. Journal of Dairy Science, 102 (Suppl 2) Abst; 102.

Pate JL and Hughes CK. 2018. Applications of large-scale molecular profiling techniques to the study of the corpus luteum. Proc 10th Intl Ruminant Reproduction Symposium, Foz do Iguacu, Brazil

Ealy AD. 2019. Early Diagnosis of Pregnancy Loss. American Dairy Science Association Annual Meeting, Cincinnati OH.

Wooldridge LK, Johnson SE and Ealy AD. 2019. Interleukin-6 increases inner cell mass and hypoblast cell numbers in bovine blastocysts. Society for the Study of Reproduction 52nd Annual Meeting, San Jose CA.

Wooldridge LK and Ealy AD. 2019. STAT3 is required for hypoblast lineage development in bovine blastocysts. 2019. Society for Developmental Biology 78th Annual Meeting, Boston MA.

Cushman RA, Tenley SC, Spuri-Gomes R, Rosasco SL, Northrop EJ, Rich JRR, McNeel AK, Summers AF, Miles JR, Chase C, Lents CA, Perry GA, Wood JR, and Cupp AS. 2018. Influence of Maternal Age on Daughter Ovarian Reserve and Reproductive Longevity in Beef Cows. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Neilson MA, Spuri-Gomes R, Romereim SM, Summers AF, Abedal-Majed MA, Tenley SC, Kurz SG, Bergman J, Davis JS, Wood JR, and Cupp AS. 2018. Altered Blood Plasma and Follicular Fluid Lipid Profiles Suggest Possible Discrepancies in Cell Signaling and Metabolism in Cows with Androgen Excess. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Snider AP, Romereim SM, Summers AF, Pohlmeier WE, McFee RM, Spuri-Gomes R, Kurz SG, Davis JS, Wood JR, and Cupp AS. 2018. Exposure to Excess Androgen in the Ovarian Microenvironment of High A4 Cows Results in Altered Function of Granulosa Cells which may Explain Changes in Cyclicity and Response to Male Exposure. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Hart ML, Abedal-Majed MA, Spuri-Gomes R, Snider AP, Kurz SG, Bergman JW, McFee RM, Casey CA, Davis JS, Cushman RA, Wood JR, and Cupp AS. 2018. Cyclicity Phenotype and Ovarian Cortex Androgen Secretion in Androgen Excess Cows are Predictive of Plasma Steroid and Lipids, Liver Enzymes, and Follicular Fluid Cytokines. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Bochantin KA, Summers AF, Pohlmeier WE, Sargent KM, Kurz SG, Romereim SM, Daudu O, McFee RM, Cushman RA, Davis JS, Cupp AS, Wood JR. 2018.  Microarray Analysis Predicts that Differentially Expressed Genes in Theca Cells from Cows with High Intrafollicular Androstenedione are Regulated by ESR1 and VEGFA Signaling and Increased mRNA Stability. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Timme KR, Miller HB, and Wood JR. Signaling of Pro-Inflammatory Cytokine TNFa through NFkB-p65 Increases Gdf9 and Decreases Figla mRNAs in Oocytes of Primary Follicles. 2018. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

McCain AR, Rister AL, Wordekemper M, Dodds ED, and Wood JR. 2018. Maternal obesity due to diet or loss of satiety differentially impacts fetal growth and placental efficiency which may be due to differences in excess circulating lipids. 51st Annual Meeting of the Society for the Study of Reproduction, New Orleans, LA

Theses/Dissertations

Hester, JM. The impact of zinc deficiency during oogenesis, follicle assembly, and growth. PhD Thesis in Physiology, Pennsylvania State University. Dec 2018.

Audra Harl. 2018. Factors affecting the quality and function of the bovine periovulatory follicle. (PhD Dissertation).

Sarah McCoski. 2018. Manipulating embryonic development and endometrial function in ruminants. (PhD Dissertation).

Lundberg, Townson DH. 2019 Investigation of Transforming Growth Factor-α and its potential role in promoting ovarian follicular dominance. UVM MS Thesis

Active collaboration within the group

NY, PA, NH, VT and WV:  Samples collected to investigate associations between fertility outcomes and SNP in candidate genes from dairy cows.

IA and UK: Samples shared to determine the effect of LPS treatment on ovarian inflammation.

PA and WV: Samples shared for analysis of molecular regulators of luteal function.

VT and NY: Samples assayed (NY) for analysis of progesterone concentrations.

In addition to Hatch Multistate Funds, these studies were supported by:

Iowa Pork Producers Association                                                                                               

National Pork Board

ISU Nutritional Sciences Council Martin Fund    

National Institute of Environmental Health Science - Agriculture and Food Research Initiative

National Institutes of Health

C. Lee Rumberger and Family Endowment

John L. Pratt Animal Nutrition Program

Virginia Agricultural Council Research Funding

University of Nebraska Foundation Funds