{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:40:29Z","timestamp":1784774429151,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The aim was to elucidate the impact of oral folic acid (FA) supplements on progesterone profile, blood metabolites and biochemical indices of heat-stressed Holstein cows during the early stage of pregnancy. The study lasted from the day of artificial insemination through the end of the fourth week of pregnancy. The first group (CON, n = 17) received 0 \u03bcg of FA\/kg BW as a control. The second and third groups received oral FA doses of 5 (FA5, n = 19) and 10 (FA10, n = 20) \u03bcg kg\u22121 BW, respectively. At the 2nd and 3rd weeks of pregnancy, the FA10 group had greater progesterone levels than the CON group (p &lt; 0.05). The FA10 group had a greater progesterone level than the FA5 and CON groups at the fourth week of pregnancy (p &lt; 0.01). The FA10 group had higher folate levels than CON group during the first three weeks of pregnancy (p &lt; 0.01). Both FA-supplemented groups had significantly greater serum folates than the CON group by the end of the fourth week of pregnancy (p &lt; 0.01). At the 2nd and 4th weeks of pregnancy, the FA10 group had greater levels of serum glucose and globulin than the CON group (p = 0.028 and 0.049, respectively). Both FA-supplemented groups had greater serum growth hormone (GH) levels at the 4th week of pregnancy (p = 0.020). Additionally, the FA10 group showed significantly higher levels of IGF-1 at the 2nd and 4th week of gestation (p = 0.040 and 0.001, respectively). FA supplementation decreased the levels of non-esterified fatty acid (NEFA) at the 2nd and 4th week of gestation (p = 0.020 and 0.035, respectively). Additionally, the FA10 group showed significantly higher pregnancy-associated glycoprotein (PAG) levels at the 2nd and 4th week of gestation (p = 0.005 and 0.001, respectively). In conclusion, oral FA supplementation (10 mcg kg\u22121) in the first month of gestation improved the progesterone profile, as well as blood folates, PAG, GH, and IGF-1 concentrations in heat-stressed Holstein cows. These findings could be useful in developing practical strategies to keep dairy cows\u2019 regular reproductive patterns under heat stress conditions.<\/jats:p>","DOI":"10.3390\/ani12151872","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:53:45Z","timestamp":1658494425000},"page":"1872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Folic Acid Supplements on Progesterone Profile and Blood Metabolites of Heat-Stressed Holstein Cows during the Early Stage of Pregnancy"],"prefix":"10.3390","volume":"12","author":[{"given":"Abdelrahman A.","family":"Kilany","sequence":"first","affiliation":[{"name":"Radioisotopes Applications Division, Department of Biological Applications, NRC, Egyptian Atomic Energy Authority, Inshas, Cairo P.O. Box 13759, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Halim A.","family":"El-Darawany","sequence":"additional","affiliation":[{"name":"Department of Animal Production, Faculty of Agriculture, Zagazig University, Zagazig P.O. Box 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram A.","family":"El-Tarabany","sequence":"additional","affiliation":[{"name":"Radioisotopes Applications Division, Department of Biological Applications, NRC, Egyptian Atomic Energy Authority, Inshas, Cairo P.O. Box 13759, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M.","family":"Al-Marakby","sequence":"additional","affiliation":[{"name":"Department of Animal Production, Faculty of Agriculture, Zagazig University, Zagazig P.O. Box 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3168\/jds.S0022-0302(97)76051-X","article-title":"Estimation of genetic variation in the interval from calving to postpartum ovulation of dairy cows","volume":"80","author":"Darwash","year":"1997","journal-title":"J. Dairy Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0093-691X(00)00305-8","article-title":"Importance of inseminating only cows in estrus","volume":"53","author":"Sturman","year":"2000","journal-title":"Theriogenology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.anireprosci.2015.08.002","article-title":"Impact of thermal stress on the efficiency of ovulation synchronization protocols in Holstein cows","volume":"160","year":"2015","journal-title":"Anim. Reprod. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0378-4320(00)00102-0","article-title":"Impaired reproduction in heat-stressed dairy cattle: Basic and applied aspects","volume":"60\u201361","author":"Wolfenson","year":"2000","journal-title":"Anim. Reprod. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E104","DOI":"10.3168\/jds.S0022-0302(03)74043-0","article-title":"Effects of heat stress on reproduction","volume":"86","author":"Jordan","year":"2003","journal-title":"J. Dairy Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2527\/1997.77suppl_236x","article-title":"Strategies for managing reproduction in the heat-stressed dairy cow","volume":"77","author":"Hansen","year":"1999","journal-title":"J. Anim. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/jn\/130.2.129","article-title":"Folate and carcinogenesis: An integrated scheme","volume":"130","author":"Choi","year":"2000","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.brainres.2008.07.077","article-title":"Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate\/methyl-deficient diet","volume":"1237","author":"Pogribny","year":"2008","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Khan, M.Z., Khan, A., Xiao, J., Dou, J., Liu, L., and Yu, Y. (2020). Overview of folic acid supplementation alone or in combination with vitamin B12 in dairy cattle during periparturient period. Metabolites, 10.","DOI":"10.3390\/metabo10060263"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s00335-009-9207-4","article-title":"A novel approach identified the FOLR1 gene, a putative regulator of milk protein synthesis","volume":"20","author":"Menzies","year":"2009","journal-title":"Mamm. Genome"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3168\/jds.S0022-0302(06)72082-3","article-title":"Dietary forage and nonfiber carbohydrate contents influence B-vitamin Intake, duodenal flow, and apparent ruminal synthesis in lactating dairy cows","volume":"89","author":"Schwab","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1093\/jn\/136.6.1522","article-title":"A folate and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats","volume":"136","author":"Ghoshal","year":"2006","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"389","DOI":"10.4141\/A05-012","article-title":"Effects of the forage to concentrate ratio on B-vitamin concentrations in different ruminal fractions of dairy cows","volume":"85","author":"Santschi","year":"2005","journal-title":"Can. J. Anim. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.3168\/jds.S0022-0302(06)72193-2","article-title":"Major advances associated with environmental effects on dairy cattle","volume":"89","author":"Collier","year":"2006","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.3168\/jds.S0022-0302(89)79483-2","article-title":"Serum folates in gestating and lactating dairy cows","volume":"72","author":"Tremblay","year":"1989","journal-title":"J. Dairy Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.3168\/jds.S0022-0302(98)75705-4","article-title":"Dietary supplements of folic acid during lactation: Effects on the performance of dairy cows","volume":"81","author":"Girard","year":"1998","journal-title":"J. Dairy Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.3168\/jds.2013-7369","article-title":"Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds","volume":"97","author":"Duplessis","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.ajog.2004.02.018","article-title":"Periconceptional folic acid\/multivitamin supplementation and twin pregnancy","volume":"191","author":"Czeizel","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7797","DOI":"10.3168\/jds.2015-9623","article-title":"Effects of intramuscular administration of folic acid and vitamin B12 on granulosa cells gene expression in postpartum dairy cows","volume":"98","author":"Gagnon","year":"2015","journal-title":"J. Dairy Sci."},{"key":"ref_20","unstructured":"National Research Council (2001). Nutrient Requirements of Dairy Cattle, National Academies Press. [7th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.livsci.2009.04.004","article-title":"Season and physiological status affects the circadian body temperature rhythm of dairy cows","volume":"125","author":"Kendall","year":"2009","journal-title":"Livest. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11250-019-02017-7","article-title":"Folic acid and flaxseed oil supplements in Ossimi ewes: Effect on body weight changes, progesterone profile, blood chemistry, and litter traits","volume":"52","author":"Atta","year":"2020","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0739-7240(01)00127-8","article-title":"Seasonal differences in progesterone production by luteinized bovine thecal and granulosa cells","volume":"22","author":"Wolfenson","year":"2002","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1093\/af\/vfy027","article-title":"Impact of heat stress on cow reproduction and fertility","volume":"9","author":"Wolfenson","year":"2019","journal-title":"Anim. Front."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.anireprosci.2003.12.009","article-title":"Factors affecting retention of early pregnancy in dairy cattle","volume":"84","author":"Starbuck","year":"2004","journal-title":"Anim. Reprod. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1439-0531.2012.01992.x","article-title":"Effects of folic acid on the development and oxidative stress of mouse embryos exposed to heat stress","volume":"47","author":"Koyama","year":"2012","journal-title":"Reprod. Domest. Anim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1093\/jn\/129.11.2070","article-title":"Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring","volume":"129","author":"Shin","year":"1999","journal-title":"J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1439-0531.1999.tb01250.x","article-title":"The influence of progesterone during early pregnancy in cattle","volume":"34","author":"Mann","year":"1999","journal-title":"Reprod. Domen. Anim."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3168\/jds.S0022-0302(95)76649-8","article-title":"Gestation and lactation of dairy cows: A role for folic acid?","volume":"78","author":"Girard","year":"1995","journal-title":"J. Dairy Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.anifeedsci.2016.01.005","article-title":"Effects of dietary supplements of rumen-protected folic acid on lactation performance, energy balance, blood parameters and reproductive performance in dairy cows","volume":"213","author":"Li","year":"2016","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.3168\/jds.2006-718","article-title":"Effects of dietary supplements of folic acid and vitamin B12 on metabolism of dairy cows in early lactation","volume":"90","author":"Graulet","year":"2007","journal-title":"J. Dairy Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cvfa.2013.04.002","article-title":"Insulin resistance in dairy cows","volume":"29","author":"Opsomer","year":"2013","journal-title":"Vet. Clin. Food Anim. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physiolgenomics.00064.2009","article-title":"Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows","volume":"39","author":"Wathes","year":"2009","journal-title":"Physiol. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0749-0720(15)30111-0","article-title":"Variability characteristics and test selection in herd-level nutritional metabolic profle testing","volume":"16","author":"Herdt","year":"2000","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114364","DOI":"10.1016\/j.anifeedsci.2019.114364","article-title":"Effects of rumen-protected folic acid addition in maternal and post-weaning diets on growth performance, total tract digestibility, ruminal fermentation and blood metabolites in lambs","volume":"260","author":"Li","year":"2020","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.3168\/jds.2016-12381","article-title":"Effects of intramuscular injections of folic acid, vitamin B12, or both, on lactational performance and energy status of multiparous dairy cows","volume":"100","author":"Duplessis","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"382","DOI":"10.15232\/S1080-7446(15)31131-1","article-title":"Relationships between Blood Urea Nitrogen and Energy Balance or Measures of Tissue Mobilization in Holstein Cows During the Periparturient Period","volume":"22","author":"Rastani","year":"2006","journal-title":"Profess Anim. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.5713\/ajas.2008.70392","article-title":"Metabolic characteristic of the liver of dairy cows during ketosis based on comparative proteomics","volume":"21","author":"Xu","year":"2008","journal-title":"Asian-Aust. J. Anim. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.beem.2005.07.011","article-title":"Insulin-like growth factor I, growth hormone and insulin in white adipose tissue","volume":"19","author":"Kratzsch","year":"2005","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"366","DOI":"10.5713\/ajas.2010.90355","article-title":"Effects of volatile fatty acids on IGF-I, IGFBP-3, GH, insulin and glucagon in plasma, and IGF-I and IGFBP-3 in different tissues of growing sheep nourished by total intragastric infusions","volume":"23","author":"Zhao","year":"2010","journal-title":"Asian-Aust. J. Anim. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.2527\/2002.8061528x","article-title":"Effect of nutrient intake on the development of the somatotropic axis and its responsiveness to GH in Holstein bull calves","volume":"80","author":"Smith","year":"2002","journal-title":"J. Anim. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wang, B., Li, Z., Li, H., Luo, H., Blair, H.T., Jian, L., and Diao, Z. (2020). Effect of dietary folic acid supplementation during pregnancy on blood characteristics and milk composition of ewes. Animals, 10.","DOI":"10.3390\/ani10030433"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4141\/A97-091","article-title":"Plane of nutrition and folic acid supplementation between birth and four months of age on mammary development of dairy heifers","volume":"79","author":"Petitclerc","year":"1999","journal-title":"Can. J. Anim. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1016\/j.theriogenology.2006.05.016","article-title":"Pregnancy associated glycoproteins (PAG) in postpartum cows, ewes, goats and their offspring","volume":"66","author":"Haugejorden","year":"2006","journal-title":"Theriogenology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.3168\/jds.2015-10192","article-title":"Circulating concentrations of bovine pregnancy-associated glycoproteins and late embryonic mortality in lactating dairy herds","volume":"99","author":"Pohler","year":"2016","journal-title":"J. Dairy Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.theriogenology.2007.03.010","article-title":"Influence of progesterone concentrations on secretory functions of trophoblast and pituitary during the first trimester of pregnancy in dairy cattle","volume":"67","author":"Ayad","year":"2007","journal-title":"Theriogenology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.3168\/jds.2014-8974","article-title":"Factors associated with pregnancy-associated glycoprotein (PAG) levels in plasma and milk of Holstein cows during early pregnancy and their effect on the accuracy of pregnancy diagnosis","volume":"98","author":"Ricci","year":"2015","journal-title":"J. Dairy Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102951","DOI":"10.1016\/j.jtherbio.2021.102951","article-title":"Early embryo losses, progesterone and pregnancy associated glycoproteins levels during summer heat stress in dairy cows","volume":"98","author":"Nanas","year":"2021","journal-title":"J. Therm. Biol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/15\/1872\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:42Z","timestamp":1760140482000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/15\/1872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ani12151872"],"URL":"https:\/\/doi.org\/10.3390\/ani12151872","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}