SAES-422 Multistate Research Activity Accomplishments Report

Status: Approved

Basic Information

Participants

Bridges, Phillip (pbrid2@email.uky.edu) Univ Kentucky; Butler, Ron (wrb2@cornell.edu) Cornell Univ;;Dailey, Robert (rdailey@wvu.edu) West Virginia Univ;;Diaz, Francisco (fjd10@psu.edu) Penn St Univ;;Flores, Jorge (jflores@wvu.edu) West Virginia Univ;;Fissore, Rafael (rfissore@vasci.umass.edu) Univ Massachusetts Amherst;;Fortune, Joanne (jf11@cornell.edu) Cornell Univ;;Giordano, Julio (jog25@cornell.edu) Cornell Univ;;Inskeep, Keith (einskeep@wvu.edu) West Virginia Univ;;Keating, Aileen (akeating@iastate.edu) Iowa StUniv;;Memili, Erdogan (em149@ads.msstate.edu)Mississippi St Univ;;Milvae, Robert (robert.milvae@uconn.edu) Univ Connecticut;;Ott, Troy (tlo12@psu.edu) Penn St Univ;;Pate, Joy (jlp36@psu.edu) Penn St Univ;;Rhoads, Shelly (rhoadsm@vt.edu) Virginia Tech Univ;;Townson, Dave (dave.townson@unh.edu) Univ New Hampshire;;Tsang, Paul (paul.tsang@unh.edu) Univ New Hampshire;;Wiltbank, Milo (wiltbank@wisc.edu) Univ Wisconsin;;Wood, Jennifer (jwood5@unl.edu) Univ Nebraska Lincoln;;Yao, Jianbo (jianbo.yao@mail.wvu.edu) West Virginia Univ; Administrator: Thompson, Gary (gat10@psu.edu) Penn St Univ;

Accomplishments

Objective 1: Identify intracellular signaling pathways and gene expression regulatory mechanisms within the ovary, embryo, or female reproductive tract that promote oocyte growth and maturation, fertilization, early embryonic development, and establishment and maintenance of pregnancy

• Identified small RNAs that were differentially expressed in non-pregnant v. pregnant CL

• Showed functional roles for the oocyte-specific RNAs KPNA7 and ZNFO in the bovine oocyte/embryo

• Identified differences in calcium channel and carrier protein expression in developing vs. mature CL

• Demonstrated differences in the ability of mural granulosa cells from fertile and infertile patients to respond to hCG

• Showed that increased photoperiod in combination with melatonin treatment has breed-dependent effects on estrous response and pregnancy rate in fall born ewe-lambs.

• Identified mRNAs and microRNAs that are differentially expressed in the epithelial cells of the oviduct when under an estradiol- versus progesterone-dominant steroidal environment.

• Showed that plasma levels of the negative acute phase protein Paraoxonase 1 (PON1) were higher in pregnant vs. open cows but were similar in healthy vs. sick cows.

• Established that dairy cows with Growth Hormone Receptor (GHR) Alu1(-/-) SNP have higher dry matter intake which better meets milk production (NEL) requirements, and consequently they have less negative energy balance compared to the other genotypes (-/+ and +/+). This finding is important because early ovulation in postpartum dairy cows which is strongly associated with higher pregnancy rates during lactation is also associated with less negative energy balance (NEBAL).

• Showed that estradiol and progesterone act independently to inhibit follicle formation and capacity of follicles to activate in fetal bovine ovaries. The effects of estradiol on fetal ovaries are mediated through one or both nuclear ERs.

• The ER modulator tamoxifen also affects the morphological development of the prepubertal reproductive tract including the ovaries.

• Heat stress and obesity alters ovarian PI3K and steroidogenic signaling. Obesity also leads to low level DNA damage, DNA damage repair response, alteration to ovarian gap junction proteins, and increased oocyte mRNAs. Obesity impacted folliculogenesis through primordial follicle activation and increased the ovotoxicant sensitivity of the ovary. It also led to increased progesterone and decreased estradiol in the serum just after ovulation.

• Determined that increased dose of PGF in the Double-Ovsynch protocol increased CL regression and fertility in multiparous dairy cows. Determined that increased dose of GnRH in Double-Ovsynch increased ovulation but did not increase fertility.

• Determined that acute feed restriction improved fertilization and embryo quality in cows that were superovulated using an FSH product with higher LH content. However, using an FSH product with higher LH content compared to a low LH product was inhibitory to fertilization and embryo quality in late lactation cows that were full fed.

• Determined that deep-horn AI did not improve fertility in dairy cows that had been subjected to superovulation. However, subclinical endometritis decreased percentage of ova that were fertilized and tended to decrease embryo recovery.

• Determined that BCS loss from calving until 21 d postpartum was related to fertility in lactating dairy cows. Further, cows that had the greatest postpartum loss of weight had a reduction in percentage of embryos that were good quality.

• HPLC-MS/MS analysis of follicular fluid showed that DHEA, androstenedione, testosterone, estrogen and estrone were increased in a sub-population of cows. High steroid cows had a decreased calving rate as heifers (~13%) and tend to leave the herd at a 2:1 ratio. Microarray analyses and candidate gene approaches suggest novel mechanisms differentially regulating steroid synthesis in high steroid cows.

Objective 2: Identify inter-cellular interactions between somatic cells of the ovary, somatic cells and germ cells, or somatic cells and the embryo that promote follicular growth, oocyte maturation, early embryonic development, and establishment and maintenance of pregnancy.

• Showed that zinc deficiency only during oocyte growth and maturation impairs embryonic development, placental development, and increases the incidence of neural tube defects

• In vitro maturation of cumulus-oocyte complexes in 75% follicular fluid is optimal for cumulus cell expansion, but does not improve blastocyst rate following in vitro fertilization.

• Several methods and in vitro systems were developed including serum free bovine monocyte cultures, a serum-free bovine granulosa cell culture system, and immunohistochemical methods for examination of adhesion molecule expression and leukocyte accumulation within the bovine corpus luteum.

• Maternal recognition of pregnancy induces changes in expression of specific miRNA in the CL. Target prediction analysis indicates that the differentially expressed miRNA are potential regulators of two pathways important to luteolysis/luteal rescue, namely apoptosis and immune response mechanisms.

• Demonstrated that freshly isolated CD45+ cells isolated from regressing CL contain a greater concentration of iNOS mRNA and lesser concentration of CD163 mRNA than midcycle CL suggesting a shift in macrophage phenotype to M1. Macrophages derived from midcycle and regressing CL exhibited differential gene expression, but macrophage phenotype could not be clearly discerned in cultured cells.

• Established that during early pregnancy in cattle, embryonic signals, including IFN tau, may promote development of tolerogenic macrophages and dendritic cells as well as changes in gene expression and altered cytokine secretion in the endometrium which may be required for successful establishment of pregnancy.

• Found that CCN1 mRNA expression in bovine granulosa cells is rapidly induced by serum provides insight about the cellular pathways that regulate the angiogenic process associated with the follicular-luteal transition in the ovary.

• Correlations between early pregnancy losses and ovarian dynamics were measured in dairy cows. Based on partial data we observed: (1) cows that underwent pregnancy loss were less likely to undergo complete luteal regression, had delayed luteal regression, and had extended inter ovulatory intervals, (2) differences in inter ovulatory intervals were due to delayed luteal regression rather than alterations in follicular wave dynamics , and (3) longer inter ovulatory intervals for open than cyclic cows may have been caused by undetected EM.

Plans for Next Reporting Period:

• Studies that define molecular mechanisms regulating follicular, oocyte, CL, and/or reproductive tract physiological function will be carried out. The outcome of these studies will potentially be used to improve the manipulation of the estrous cycle and improve AI, conception, and pregnancy rates

• In vivo studies to improve AI protocols as well as test the effect of diet supplementation, determine the effects of mastitis, heat stress, and body condition, and document the implications of pregnancy losses on reproduction efficiency and culling dynamics of the herd will be undertaken.

• Continue the collaborative project assessing the incidence of the GHR AluI (-/-) SNP in dairy cows and the implications of this SNP on negative energy balance and reproductive performance in lactating dairy cows.

Impacts

  1. Increased understanding of how the pool of resting follicles is formed and of the signals that allow or inhibit activation and subsequent growth is of potential practical importance because the size of the ?follicular reserve? has been linked to fertility in cattle.
  2. Defining links between alterations in central metabolism during obesity and heat stress and negative impacts on ovarian function and oocyte quality will produce biological targets to ameliorate negative reproductive outcomes. Likewise understanding how environmental effects (e.g. zinc deficiency) during oocyte development negatively affect embryo/fetal and placental development will allow for therapies to better reverse these poor outcomes.
  3. Provide indications of how external factors affect the development of the prepubertal reproductive tract as well as highlight the importance of the content of the follicular fluid on the maturation of the cumulus-oocyte complexes.
  4. Greater understanding of gene expression and mRNA stability during folliculogenesis, oocyte maturation, and early embryogenesis will enable solutions to reverse early embryonic loss that continues to limit reproductive success.
  5. Basic studies continue to increase our information on regulation of luteal function and maintenance during the estrous cycle in ruminants, specifically in regard to actions on calcium flux and signaling and miRNA modulation of immune response at maternal recognition of pregnancy.
  6. Implementing different post-implantation hormonal treatments based on specific infertility cause could lead to increased pregnancy rates while keeping the number of multiple gestations low.
  7. By understanding the effect of ovarian steroids on oviductal epithelial cell function, breeding protocols can be designed to maximize the ability of the oviduct to facilitate fertilization and early embryonic development.
  8. In dairy cows paraoxonase1 is transferred to ovarian follicular fluid from blood and becomes available to protect oocytes from local metabolic/oxidative damage and could thereby enhance fertility during breeding.
  9. The presence of the growth hormone receptor (GHR) AluI(-/-) allele in Holstein cows is associated with increased serum IGF-I concentrations and a shorter calving to conception interval during lactation ie. higher fertility.
  10. By acquiring new fundamental knowledge of how the building of the blood vessel network is regulated in the follicle and the corpus luteum, how signal transduction mechanism influence granulosa cell fate, and how immune cell accumulation within the corpus luteum affects luteal function, these efforts will lead to more effective/targeted strategies to lower infertility rate and increase income to dairy producers.
  11. Cows that undergo pregnancy loss present delayed luteal regression and extended inter ovulatory intervals which delays time to re-insemination and impairs subsequent reproductive performance.
  12. The development of a bovine monocyte culture system can be used to produce in vitro differentiated macrophages and provide the information needed to classify bovine macrophages as M1 or M2 and better understand the role of immune cells on establishment of pregnancy.

Publications

Peer Reviewed Research Articles

Matthews, J.C., Z. Zhang, J.D. Patterson, P.J. Bridges, A.J. Stromberg and J.A. Boling. 2014. Hepatic transcriptome profiles differ among maturing beef heifers supplemented with inorganic, organic, or mixed (50% Inorganic:50% Organic) forms of dietary selenium. Biological Trace Element Research. Accepted.

Schneider, A., V. Absalon-Medina, G. Esposito, M. N. Corrêa, and W. R. Butler. Paraoxonase (PON) 1, 2 and 3 expression in granulosa cells and PON1 activity in follicular fluid of dairy cows. Reprod.Dom.Anim. 48:989-994, 2013.

Schneider, A., M. N. Corrêa, and W. R. Butler. Association between growth hormone receptor AluI polymorphism and fertility of Holstein cows. Theriogenology 80:1061-1066, 2013.

Esposito, G.,V. A. Absalón Medina, A. Schneider, R. O. Gilbert, and W. R. Butler. Effect of dietary conjugated linoleic acid (CLA) on the metabolism and reproduction of dairy cows. South African Journal of Animal Science 43 (Supplement 1):S33-S37, 2013.

Tripurani SK, Wee G, Lee KB, Smith GW, Wang L and Yao J. 2013. MicroRNA-212 post-transcriptionally regulates oocyte-specific basic-helix-loop-helix transcription factor, factor in the germline alpha (FIGLA), during bovine early embryogenesis. PLoS ONE 8(9): e76114. doi:10.1371/journal.pone.0076114.

Holler,Tammy L., Matthew Dean, Todd Taylor, Daniel H. Poole, M. L. Thonney, D. L. Thomas, J. L. Pate, N. Whitley, R. A. Dailey, and E. K. Inskeep. 2014. Effects of service sire on prenatal mortality and prolificacy in ewes. J ANIM SCI jas.2013-7489; published ahead of print April 28, 2014, doi:10.2527/jas.2013-7489.

Wright, M. F., E. Bowdridge, E. L. McDermott, S. Richardson, J. Scheidler, E. K. Inskeep and J. A. Flores. 2014. Mechanisms of intracellular calcium homeostasis in the developing and mature bovine corpora lutea. Biol. Reprod. 90:1-12.

Tian X, Anthony K, Neuberger T and Diaz FJ. 2014. Preconception zinc deficiency disrupts postimplantation fetal and placental development. Biology of Reproduction 90(4)83, 1-12.

Poole, DH, Ndiaye, K, Pate, JL. 2013. Expression and regulation of secreted phosphoprotein 1 in the bovine corpus luteum and effects on T lymphocyte chemotaxis. Reproduction 146, 527-537

Oh, J, Hristov, AN, Lee, C, Cassidy, T, Heyler, K, Varga, GA, Pate, J, Walusimbi, S, Brzezicka, E, Toyokawa, K, Werner, J, Donkin, SS, Elias, R, Dowd, S, Bravo, D. 2013. Immune and production responses of dairy cows to postruminal supplementation with phytonutrients. J Dairy Sci 96, 7830-7843

Walusimbi SS, Pate JL. 2014. Luteal cells from functional and regressing corpora lutea differentially alter the function of gamma-delta T cells. Biol. Reprod. (in press)

Ribeiro ES, Bruno RG, Farias AM, Hernández-Rivera JA, Gomes GC, Surjus R, Becker LF, Birt A, Ott TL, Branen JR, Sasser RG, Keisler DH, Thatcher WW, Bilby TR, Santos JE. 2014. Low doses of bovine somatotropin enhance conceptus development and fertility in lactating dairy cows. Biol. Reprod. 90(1):10.

Nteeba, J., Perfield, J.W., Ross, J.W., Keating, A.F. 2013. High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression. Reproductive Toxicology 42: 68-77.

Nteeba, J., Ortinau L.C., Perfield, J.W. II, Keating, A.F. 2013. Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues. Molecular Reproduction and Development. 80(11):948-58.

Ganesan, S., Bhattacharya, P., Keating, A.F. 2013. 7,12-dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries. Toxicology and Applied Pharmacology.272: 690-69. ISU Toxicology Program Patricia A. Murphy High Impact Publication Award.

Mani, V., Harris, A.J., Keating, A.F., Weber, T.E. Dekkers, J.C.M., and Gabler. N.K. 2013. Intestinal integrity, endotoxin transport and detoxification in pigs divergently selected for residual feed intake. Journal of Animal Science. 91(5):2141-50.

Bhattacharya, P., Madden, J.A., Sen, N., Hoyer, P.B., and Keating, A.F. 2013. Glutathione S-transferase class mu regulation of apoptosis signal-related kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries. Toxicology and Applied Pharmacology. 267(1):49-56.

Deaver, S.E., A.M. Felix and M.L. Rhoads. 2014. Conception rates of lactating dairy cattle following intrauterine administration of a prostaglandin F2? receptor antagonist four days after insemination. Theriogenology. (submitted).

Field, M.E., S.E. Deaver, R.P. Rhoads, R.J. Collier and M.L. Rhoads. 2013. Effects of prolonged nutrient restriction on baseline and periprandial plasma ghrelin concentrations of postpubertal Holstein heifers. J. Dairy Sci. 96(10):6473-6479.

Penrod, L.V., R.E. Allen, M.L. Rhoads, S.W. Limesand and M.J. Arns. 2013. Oxytocin stimulated release of PGF2? and its inhibition by a cyclooxygenase inhibitor and an oxytocin receptor antagonist from equine endometrial cultures. Anim. Reprod. Sci. 139(1-4):69-75.

Deaver, S.E., P.B. Hoyer, S.M. Dial, M.F. Field, R.J. Collier and M.L. Rhoads. 2013. Localization of ghrelin and its receptor in the reproductive tract of Holstein heifers. J. Dairy Sci. 96(1):150-157.

Foradori MJ, Chen Q, Fernandez CA, Harper J, Li X, Tsang PCW, Langer R, Moses MA (2014) Matrilin-1 is an inhibitor of angiogenesis. Journal of Biological Chemistry, 289:14301-14309. PMID: 24692560

Pereira ABD, Brito AF, Townson LL, Towson DH (2013) Assessing the research and education needs of the organic dairy industry in the northeastern United States. J. Dairy Sci. 96:7340-7348. PMID: 24054299

Bender RW, Hackbart KS, Dresch AR, Carvalho PD, Vieira LM, Crump PM, Guenther JN, Fricke PM, Shaver RD, Combs DK, Wiltbank MC. 2014. Effects of acute feed restriction combined with targeted use of increasing luteinizing hormone content of follicle-stimulating hormone preparations on ovarian superstimulation, fertilization, and embryo quality in lactating dairy cows. Journal of Dairy Science 97:764-778.

Ferraretto LF, Gencoglu H, Hackbart KS, Nascimento AB, Dalla Costa F, Bender RW, Guenther JN, Shaver RD, Wiltbank MC. 2014. Effect of feed restriction on reproductive and metabolic hormones in dairy cows. Journal of Dairy Science 97:754-763.

Nascimento AB, Souza AH, Keskin A, Sartori R, Wiltbank MC. 2014. Lack of complete regression of the Day 5 corpus luteum after one or two doses of PGF?? in nonlactating Holstein cows. Theriogenology 81:389-395.

Pereira MHC, Rodriguez ADP, De Carvalho RJ, Wiltbank MC, Vasconcelos JLM. 2014. Increasing length of an estradiol and progesterone timed artificial insemination protocol decreases pregnancy losses in lactating dairy cows. Journal of Dairy Science 97:1-11.

Carvalho PD, Souza AH, Amundson MC, Hackbart KS, Fuenzalida MJ, Herlihy MM, Ayres H, Dresch AR, Vieira LM, Guenther JG, Grummer RR, Fricke PM, Shaver RD, Wiltbank MC. Relationships between fertility and postpartum changes in body condition and body weight in lactating dairy cows. Journal of Dairy Science 2014; 97:1-18.

Surjus RS, Prata AB, Borsato M, Mattos FCSZ, Martins da Silveira MC, Mourao GB, Pires AV, Wiltbank MC, Sartori R. In vivo embryo production in cows superovulated 1 or 2 days after ovum pick-up. Reproduction Fertility and Development 2014; 26:527-532.

Ayres, H., R. M. Ferreira, A. P. Cunha, R. R. Araujo, and M. C. Wiltbank. 2013. Double-Ovsynch in high-producing dairy cows: Effects on progesterone concentrations and ovulation to GnRH treatments. Theriogenology 79:159-164.

Carvalho, P. D., A. H. Souza, R. Sartori, K. S. Hackbart, A. R. Dresch, L. M. Vieira, P. S. Baruselli, J. N. Guenther, P. M. Fricke, R. D. Shaver, and M. C. Wiltbank. 2013. Effects of deep-horn AI on fertilization and embryo production in superovulated cows and heifers. Theriogenology 80:1074-1081.

Diaz, F. J., W. Luo, and M. C. Wiltbank. 2013. Prostaglandin F2alpha regulation of mRNA for activating protein 1 transcriptional factors in porcine corpora lutea (CL): lack of induction of JUN and JUND in CL without luteolytic capacity. Domestic Animal Endocrinology 44:98-108.

Giordano, J. O., M. C. Wiltbank, P. M. Fricke, S. Bas, R. A. Pawlisch, J. N. Guenther, and A. B. Nascimento. 2013. Effect of increasing GnRH and PGF?? during Double-Ovsynch on ovulatory response, luteal regression, and fertility of lactating dairy cows. Theriogenology 80:773-783..

Hackbart, K. S., P. M. Cunha, R. K. Meyer, and M. C. Wiltbank. 2013. Effect of Glucocorticoid-Induced Insulin Resistance on Follicle Development and Ovulation. Biology of Reproduction 88(6):1-12.

Lopes, G., Jr., J. O. Giordano, A. Valenza, M. M. Herlihy, J. N. Guenther, M. C. Wiltbank, and P. M. Fricke. 2013. Effect of timing of initiation of resynchronization and presynchronization with gonadotropin-releasing hormone on fertility of resynchronized inseminations in lactating dairy cows. Journal of Dairy Science 96(6):3788-3798.

Nascimento AB, Souza AH, Sartori R, Wiltbank MC. 2013. Progesterone production and metabolism and its role before, during, and after artificial insemination influencing the fertility of high producing dairy cows. Acta Scientiae Veterinariea 41:1-14

Nascimento, A. B., A. H. Souza, J. N. Guenther, F. P. D. Costa, R. Sartori, and M. C. Wiltbank. 2013. Effects of treatment with human chorionic gonadotrophin or intravaginal progesterone-releasing device after AI on circulating progesterone concentrations in lactating dairy cows. Reproduction, Fertility and Development 25:818-824.

Nascimento, A. B., R. W. Bender, A. H. Souza, H. Ayres, R. R. Araujo, J. N. Guenther, R. Sartori, and M. C. Wiltbank. 2013. Effect of treatment with human chorionic gonadotropin on day 5 after timed artificial insemination on fertility of lactating dairy cows. Journal of Dairy Science 96(5):2873-2882.

Penagaricano, F., A. H. Souza, P. D. Carvahlo, A. M. Driver, G. Rocio, K. S. Hackbart, D. Luchini, R. D. Shaver, M. C. Wiltbank, and H. Khatib. 2013. Effect of maternal methionine supplementation on the transcriptome of bovine preimplantation embryos. PLoS ONE 8:e72302.

Pereira, M. H. C., A. D. P. Rodrigues, T. Martins, W. V. C. Oliveira, P. S. A. Silveira, M. C. Wiltbank, and J. L. M. Vasconcelos. 2013. Timed artificial insemination programs during the summer in lactating dairy cows: Comparison of the 5-d Cosynch protocol with an estrogen/progesterone-based protocol. Journal of Dairy Science 96:6904-6914.

Pereira, M. H. C., C. P. Sanches, T. G. Guida, A. D. R. Rodrigues, F. L. Aragon, M. B. Veras, P. T. Borges, M. C. Wiltbank, and J. L. M. Vasconcelos. 2013. Timing of prostaglandin F-2 alpha treatment in an estrogen-based protocol for timed artificial insemination or timed embryo transfer in lactating dairy cows. Journal of Dairy Science 96:2837-2846.

Piccinato, C. A., G. J. M. Rosa, A. U. N'Jai, C. R. Jefcoate, and M. C. Wiltbank. 2013. Estradiol and Progesterone Exhibit Similar Patterns of Hepatic Gene Expression Regulation in the Bovine Model. PLoS ONE 8:e73552.

Vasconcelos, J. L. M., M. H. C. Pereira, M. Meneghetti, C. C. Dias, O. G. SaFilho, R. F. G. Peres, A. D. P. Rodrigues, and M. C. Wiltbank. 2013. Relationships between growth of the preovulatory follicle and gestation success in lactating dairy cows. Animal Reproduction 10:206-214.

Pohlmeier WE, Xie F, Kurz SG, Lu N, and Wood JR (2014) Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of RNAs stored in the ovulated oocyte, Mol Reprod Dev (in press), PMID:24824196

McFee RM, Artac RA, Summers AF, Pohlmeier WE, Brauer VM, Kurz SG, Cushman RA, Wood JR, and Cupp AS (2014). Vascular Endothelial Growth Factor A isoform expression differs prior to and after the LH surge and the ratio of these isoforms may be a marker of follicle health. Reprod (under revision)

Summers AF, Pohlmeier WE, Brauer VM, Sargent KM, Kurz SG, McFee RM, Cushman RA, Cupp AS, and Wood JR (2014). Altered theca gene expression and ovarian follicular development in cows with follicular fluid androgen excess PLOS One (under revision)

Baier SR, Nguyen C, Xie F, Wood JR, and Zempleni J (2014) MicroRNA from cow’s milk are bioavailable and affect gene expression in humans J Nutr (under revision)

Book Chapters and Review Articles

Goodman, R. L. and E. K. Inskeep. 2014. Control of the Ovarian Cycle of the Sheep. Chapter 28 in Knobil and Neill’s Physiology of Reproduction. Edited by Tony Plant and Tony Zeleznik, 47 pages (In Press).

Matthews, J.C. and P.J. Bridges. 2014. NutriPhysioGenomics: What do they tell us about adaptation of cattle to nutritional, physiological and health challenges? Animal Production Science. Submitted

Fortune, J.E., M.Y. Yang, J.J. Allen, and S.L. Herrick, 2013. The ovarian follicular reserve in cattle: What regulates its formation and size? J. Anim. Sci. 91:3041-3050.

Wiltbank, MC and Pursley JR. 2014. The cow as an induced ovulator: Timed AI after synchronization of ovulation. Theriogenology 81:170-185

Wiltbank MC, Souza AH, Carvahlo PA, Cunha AP, Giordano JO, Fricke PM, Baez GM, Diskin MG. Physiological and practical effects of progesterone on reproduction in dairy cattle. Animal 2014; 8:s1:70-81.

Haughian, J. M., O. J. Ginther, F. J. Diaz, and M. C. Wiltbank. 2013. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers. Biology of Reproduction 88(6):165-177.

Hristov AN, Ott TL, Tricarico J, Rotz A, Waghorn G, Adesogan A, Dijkstra J, Montes F, Oh J, Kebreab E, Oosting SJ, Gerber PJ, Henderson B, Makkar HP, Firkins JL. 2013. Special topics--Mitigation of methane and nitrous oxide emissions from animal operations: III. A review of animal management mitigation options. J Anim. Sci. 2013 91(11): 5095-113.

Gerber PJ, Hristov AN, Henderson B, Makkar H, Oh J, Lee C, Meinen R, Montes F, Ott TL, Firkins J, Rotz A, Dell C, Adesogan AT, Yang WZ, Tricarico JM, Kebreab E, Waghorn G, Dijkstra J, Oosting S. 2013. Technical options for the mitigation of direct methane and nitrous oxide emissions from livestock: a review. Animal. Suppl 2:220-34.

Matthews, J.C. and P.J. Bridges. 2014. NutriPhysioGenomics: What do they tell us about adaptation of cattle to nutritional, physiological and health challenges? Animal Production Science. Accepted.

Conference Papers and Abstracts/Presentations

Garbacik, S., J.C. Matthews, K. Cerny and P.J. Bridges. 2013. Gestational form of supplemental selenium (Se) affects gene expression in the newborn calf testis. I. Steroidogenesis. Journal of Animal Science. Abstract W370.

Skees, C., P.J. Bridges, J. Patterson and J.C. Matthews. 2013. Gestational form of supplemental selenium (Se) affects gene expression in the newborn calf testis. II. Spermatogenesis. Journal of Animal Science. Abstract T333

Butler, W.R. Metabolic and reproductive interactions in dry and transition dairy cows. Proceedings “InCalf Reproduction Symposium 2013”, Melbourne Australia, pp 12-15.

Butler, W.R. Nutritional regulation of reproduction and fertility in dairy cattle. Proceedings “InCalf Reproduction Symposium 2013”, Melbourne Australia, pp 35-39.

Wang L, Smith GW and Yao J. MicroRNA-1296 Regulates bovine oocyte-specific Karyrophrin alpha 7 expression during maternal-zygotic transition. 46th Annual Meeting Society for the Study of Reproduction, Montréal, Québec, Canada. July 22 – 26, 2013.

Hand J, Wang L, Smith GW and Yao J. Identification of a novel oocyte-specific KRAB (Kruppel-associated box)-containing zinc finger protein in cattle. 46th Annual Meeting Society for the Study of Reproduction, Montréal, Québec, Canada. July 22 – 26, 2013.

Wang, L. Smith GW and Yao, J. Analysis of DNA methylation at the TSS region of KPNA7 gene during bovine early embryonic development. Plant and Animal Genome XXI Conference, San Diego, CA January 12-16, 2013.

Inskeep, E. K. and R. L. Goodman. 2013. Factors that affect prolificacy in sheep. Proceedings, Western Section, Am. Soc. Anim. Sci. 64:19-23.

Sun T and Diaz FJ. (2013). The effect of Lats1 mutation and SMAD signaling inhibitors on germ cell number and/or YAP/TAZ phosphorylation in mouse ovaries or granulosa cells. Proceedings of the 46th Annual Meeting of the Society for the Study of Reproduction, Montreal, Canada., Abstract #903, p. 400.

Tian X and Diaz FJ. (2013). Preconception zinc deficiency causes postimplantation embryonic loss. Proceedings of the 46th Annual Meeting of the Society for the Study of Reproduction, Montreal, Canada, Abstract #105, p.68.

Maalouf, S, Pate, JL. 2013. MicroRNA34a regulates survival and function of luteal steroidogenic cells. Biol. Reprod. 89(Suppl. 1):135

Walusimbi, SS, Pate, JL, Poole, DH, Ott, TL. 2013. Does pregnancy induce a tolerogenic environment in the bovine corpus Luteum? Biol. Reprod. 89(Suppl 1):132

Oh, J., A. N. Hristov, J. Pate, S. Walusimbi, and D. Bravo. 2013. Effect of capsicum oleoresin on proliferation of bovine peripheral blood mononuclear cells and intracellular cytokines production in vitro J. Dairy Sci. 96(Suppl. 1):592.

S Vasudevan, MM Kamat, JL Pate, TL Ott. 2014. Effects of early pregnancy on endometrial cytokines and other immune related genes in dairy heifers. American Journal of Reproductive Immunology 71 (Suppl. 1): 86

MM Kamat, S Vasudevan, D Townson, JL Pate, TL Ott. 2014. Changes in myeloid lineage cells in the endometrium of dairy heifers during the estrous cycle and early pregnancy. American Journal of Reproductive Immunology 71 (Suppl. 1): 59

Mouttham, LL, JE Fortune, P. Comizzoli, 2013. Detrimental effects of cryoprotectant exposure can be naturally overcome in fetal bovine ovarian tissues. Biology of Reproduction, Supplement, Proc. of the 46th annual meeting of the Soc. for the Study of Reproduction, Abstract #56.

Yang, MY, JE Fortune, 2013. BPA inhibits estradiol production, decreases aromatase mRNA and increases the incidence of multi-oocyte follicles in bovine fetal ovaries in vitro. Biology of Reproduction, Supplement, Proc. of the 46th annual meeting of the Soc. for the Study of Reproduction, Abstract #124.

Fortune, JE, LL Mouttham, 2013. Bone morphogenetic protein-4 (BMP-4) promotes activation of bovine primordial follicles in vitro. Biology of Reproduction, Supplement, Proc. of the 46th annual meeting of the Soc. for the Study of Reproduction, Abstract #553.

Graves, K.L., Mordhorst, B., Oldfather, N., Wright, E.C., Hale, B., Boddicker, R.L., Keating, A.F., Ross J.W. 2013 Identification of measures predictive of puberty onset. 46th Annual Meeting Society for the Study of Reproduction, Montreal, Quebec July 22-25.

Ganesan, S., Nteeba, J., Keating, A.F. 2013. Obesity alters the DNA repair response following chronic exposure to 7,12-dimethylbenz[a]anthracene in mouse ovaries. Society for the Study of Reproduction annual meeting. Platform presentation.

Madden, J.A., Keating, A.F. 2013. Glutathione depletion rescues phosphoramide mustard-induced follicle loss in rat ovaries. Society for the Study of Reproduction annual meeting.

Nteeba, J., Ganesan, S., Gray, B., and Keating, A.F. 2013. Effect of obesity on 7,12-dimethylbenz[a]anthracene-induced ovotoxicity in mice. Society for the Study of Reproduction annual meeting.

Jenkins, J.D., Gabler, N.K., Keating, A.F., Millman, S.T., Siegford, J.M., Johnson, A.K. 2013. Barrow approachability to a human when selected for feed efficiency. American Society of Animal Science annual meeting.

Madden, J.A., and Keating, A.F. 2013. Chloroethylaziridine: an ovotoxic metabolite of cyclophosphamide? Society of Toxicology annual meeting.

Ganesan, S., and Keating, A.F. 2013. Role of connexin proteins during the ovarian response to 7,12-dimethylbenz[a]anthracene exposure in rat ovaries. Society of Toxicology annual meeting.

Wood, A.Y.*, H.L.M. Tucker, V.L. McCracken, S.E. Deaver, B.M. Brown, R.M. Akers and M.L. Rhoads. 2013. Tamoxifen treatment affects morphological characteristics and gene expression within the reproductive tract of prepubertal Holstein heifers. J. Dairy Sci. J. Dairy Sci. 96(suppl 1):635.

Brown, B., J. Stallings and M. Rhoads*. 2013. Periconceptional heat stress of Holstein cows affects subsequent milk production and composition. J. Dairy Sci. 96(suppl 1):470-471.

McCracken, V.L.*, G. Xie, S.E. Deaver, L.H. Baumgard, R.P. Rhoads and M.L. Rhoads. 2013. Effects of heat stress and insulin on hepatic progesterone catabolic enzymes cytochrome P450 2C and 3A in lactating cows. J. Dairy Sci. 96(suppl 1):597.

Kohlhaas, K.S.*, J.L. Zambito, H.S. Spooner, R.C. Boston, M.L. Rhoads, J.W. Knight and R.K. Splan. 2013. Effects of oral resveratrol supplementation on insulin sensitivity and reproductive cyclicity in obese mares on pasture. J. Equine Vet. Sci. 33(5):370-371.

McCracken, V.L.*, A.Y. Wood, A.L. Zezeski, J.G. Wiegert, D.W. Lugar, J.M. Scheffler, S.W. El-Kadi, A.D. Ealy and M.L. Rhoads. Porcine pre-pubertal reproductive tract development is altered by consumption of high fructose but not high fat diets. Biol. Reprod. (in press).

Wood, A.Y., A.L. Zezeski*, V.L. McCracken, A.D. Ealy and M.L. Rhoads. Maturation of bovine cumulus oocyte complexes in media containing follicular fluid improves cumulus cell expansion without affecting the outcome of in vitro fertilization.

M.L. Rhoads. 2014 Implementing strategies to reduce heat stress in dairy herds. Ceva Sante Animale ReprodAction Cattle Symposium Nice, France

M.L. Rhoads. 2013 Metabolic adaptations to heat stress and the related implications for fertility of lactating dairy cattle. 6th Annual Conference of the Veterinary Research Division Cairo, Egypt

Coticchia C, Miseirvitch J, Cummings C, Davis JS, Tsang PCW, Moses MA (2014) Regulation of cysteine rich 61-connective tissue growth factor-nephroblastoma overexpressed (CCN1) in granulosa cells. Accepted abstract for the 47th Meeting of the Society for the Study of Reproduction.

Townson DH, Diaz FJ, Ocon-Grove OM, Johnson AL (2014) A practical in vitro approach for the investigation of bovine granulosa cells from small follicles. Accepted abstract for the 47th Meeting of the Society for the Study of Reproduction.

Robert Wijma, Matias L Stangaferro, Josh R Branen, Jeremy M Howard and Julio O Giordano, Altered ovarian dynamics in lactating dairy cows undergoing embryonic mortality. Accepted Abstract for the Animal and Dairy Science American Association Annual Meeting, 2014.

Giordano, J. O. Pregnancy losses and non-pregnancy diagnosis in dairy cattle. Dairy Health Management Certificate Program. (Attendants: ~50 veterinarians, 6 scientists, and 5 graduate students). Ontario Veterinary College, University of Guelph. June 4th, 2014.

Giordano, J. O. Reproductive physiology of dairy cattle update. Ohio Dairy Health and Management Certificate Program. (Attendants: ~10 veterinarians, 4 scientists, and 2 graduate students). College of Veterinary Medicine, The Ohio State University. May 1st, 2014.

Giordano, J. O. Management strategies for a successful first and subsequent AI services in lactating dairy cows. Vetoquinol continuing education program for bovine practitioners. (Attendants: ~55 veterinarians, 2 industry scientists, and 10 industry professionals). New York City, NY. April 21st, 2014

Xie F, Pohlmeier WE, Lu N, Smith JE, McKnite AM, Ciobanu DC, and Wood JR (2013) Genetic background determines the effect of a high fat diet on body weight, ovulation rates, ovarian steroidogenesis, and mRNA abundance of maternal effect genes in ovulated MII-arrested oocytes. Society for the Study of Reproduction 46th Annual Meeting, Montreal, Quebec, Canada

Pohlmeier WE, Xie F, Lu N, Smith JE, Wood JR (2013) Progressive obesity alters the steroidogenic response to ovulatory stimulation and increases the abundance of RNAs stored in the MII-arrested oocyte. Society for the Study of Reproduction 46th Annual Meeting, Montreal, Quebec, Canada

Summers AF, Pohlmeier WE, Brauer VM, Sargent KM, McFee RM, Cushman RA, Wood JR, and Cupp AS (2013) A bovine model for polycystic ovary syndrome. Society for the Study of Reproduction 46th Annual Meeting, Montreal, Quebec, Canada

McFee RM, Kurz SG, Summers AF, Pohlmeier WE, Wood JR, Cushman RA, and Cupp AS (2013) Granulosa cells activate different signal transduction pathways dependent on follicle health status and ability to convert androstenedione to estrogen resulting in different steroidogenic profiles for beef cattle follicles. Society for the Study of Reproduction 46th Annual Meeting, Montreal, Quebec, Canada

Extension Reports

AF Summers, WE Pohlmeier, VM Brauer, KM Sargent, RM McFee, SG Kurz, RA Cushman, JR Wood, AS Cupp. Androgen Excess in Beef Cows Results in Altered Theca Cell Gene Expression and Fertility. Nebraska Beef Report 2014.

RM McFee, R A Artac, AF Summers, WE Pohlmeier, VM Brauer, SG Kurz, RA Cushman, JR Wood, AS Cupp. Follicular vascular endothelial growth factor A expression before and after the LH surge. Nebraska Beef Report 2014.

Theses/Dissertations

Garbacik, Stefani R., "Gestational Form of Supplemental Selenium (Se) Affects Steroidogenic Gene Expression in the Newborn Calf Testis" (2014). Theses and Dissertations--Animal and Food Sciences. Paper 34. http://uknowledge.uky.edu/animalsci_etds/34

Deacon, Matthew L. 2013. The Effects of Artificial Photoperiod on Age at Puberty in Fall-born Ewe Lambs. MS Thesis West Virginia University, Morgantown WV. 46 pages.

The Role of Zinc in Ovarian Function. Dissertation in Animal Science by Xi Tian. The Pennsylvania State University. 2013

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

National Institute of Health research grants HD074831 and HD057283 to FJD.

Agriculture and Food Research Initiative Competitive Grant no. 2012-67015-30212 from the USDA National Institute of Food and Agriculture to JLP.

C. Lee Rumberger and Family Chair in Agricultural Science funds to JLP

Agriculture and Food Research Initiative Competitive Grant no. 2013-67015-2096 from the USDA National Institute of Food and Agriculture to JRW/ASC

National Pork Board, Virginia Horse Industry Board, and John Lee Pratt Animal Nutrition Program funds to MLR

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