1. bookVolume 19 (2019): Issue 3 (July 2019)
Journal Details
First Published
25 Nov 2011
Publication timeframe
4 times per year
access type Open Access

Progesterone Supplementation During the Pre-implantation Period Influences Interferon-Stimulated Gene Expression in Lactating Dairy Cows

Published Online: 30 Jul 2019
Volume & Issue: Volume 19 (2019) - Issue 3 (July 2019)
Page range: 713 - 724
Received: 12 Oct 2018
Accepted: 20 Feb 2019
Journal Details
First Published
25 Nov 2011
Publication timeframe
4 times per year

This study examined the effect of progesterone (P4) supplementation from Days 16 to 18 post-AI on interferon-stimulated gene (ISG) expression on Day 19 in high-producing dairy cows. Gene expression levels were measured in peripheral blood mononuclear cells. Possible relationships between ISG expression and the incidence of pregnancy failure were also investigated. Cows were alternately assigned on Day 16 post-AI to a control (C: n = 13) or treatment group (P4: n = 14). Out of 27 cows, 12 returned to oestrus before pregnancy diagnosis and 9 were diagnosed as pregnant on Day 28. ISG expression was assessed in all cows. Expression levels for the genes OAS1, ISG15, MX1 and MX2 were higher for pregnant than for non-pregnant cows (P=0.04; P<0.001; P=0.02; P=0.045; respectively). A significant (P=0.01) interaction was observed between the treatment and positive pregnancy diagnosis groups on Day 28 post-AI for the probability of showing ISG expression. This interaction suggests that in cows not pregnant on Day 28, P4 supplementation may have led to increased ISG15 mRNA expression on Day 19. Lower ISG15 expression was detected for cows returning to oestrus than for pregnant cows (P<0.001). However, cows with a negative pregnancy diagnosis showed intermediate values, differences being non-significant when compared to cows returning to oestrus or pregnant cows. Our results suggest that P4 supplementation during the pre-implantation period promotes conceptus signalling.


Alhussien M.N., Kamboj A., Aljader M.A., Panda B.S.K., Yadav M.L., Sharma L., Mohammed S., Sheikh A.A., Lotfan M., Kapila R., Mohanty A.K., Dang A.K. (2018). Effect of tropical thermal stress on peri-implantation immune responses in cows. Theriogenology, 114: 149–15810.1016/j.theriogenology.2018.03.036Search in Google Scholar

Ayalon N. (1978). A review of embryonic mortality in cattle. J. Reprod. Fertil., 54: 483–493.Search in Google Scholar

Binelli M., Subramaniam P., Diaz T., Johnson G.A., Hansen T.R., Badinga L., Thatcher W.W. (2001). Bovine interferon-tau stimulates the Janus kinase-signal transducer and activator of transcription pathway in bovine endometrial epithelial cells. Biol. Reprod., 64: 654–665.Search in Google Scholar

Bridges G.A., Day M.L., Geary T.W., Cruppe L.H. (2013). Triennial Reproduction Symposium: deficiencies in the uterine environment and failure to support embryonic development. J. Anim. Sci., 91: 3002–3013.Search in Google Scholar

Carter F., Forde N., Duffy P., Wade M., Fair T., Crowe M.A., Evans A.C., Kenny D.A., Roche J.F., Lonergan P. (2008). Effect of increasing progesterone concentration from Day 3 of pregnancy on subsequent embryo survival and development in beef heifers. Reprod. Fert. Develop., 20: 368–375.Search in Google Scholar

Chomczynski P., Sacchi N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction. Anal. Biochem., 162: 156–159.Search in Google Scholar

Clemente M., de La Fuente J., Fair T., Al Naib A., Gutierrez-Adan A., Roche J. F., Rizos D., Lonergan P. (2009). Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium? Reproduction, 138: 507–517.10.1530/REP-09-0152Search in Google Scholar

Committee on Bovine Reproductive Nomenclature (1972). Recommendations for standardizing bovine reproductive terms. Cornell Vet., 62: 216–237.Search in Google Scholar

Forde N., Carter F., Fair T., Crowe M.A., Evans A.C., Spencer T.E., Bazer F.W., Mc-Bride R., Boland M.P., O ’ Gaora P., Lonergan P., Roche J.F. (2009). Progesterone-regulated changes in endometrial gene expression contribute to advanced conceptus development in cattle. Biol. Reprod., 81: 784–794.Search in Google Scholar

Forde N., Spencer T.E., Bazer F.W., Song G., Roche J.F., Lonergan P. (2010). Effect of pregnancy and progesterone concentration on expression of genes encoding for transporters or secreted proteins in the bovine endometrium. Physiol. Genomics, 41: 53–62.Search in Google Scholar

Forde N., Duffy G.B., McGettigan P.A., Browne J.A., Mehta J.P., Kelly A.K., Mansouri-Attia N., Sandra O., Loftus B.J., Crowe M.A., Fair T., Roche J.F., Lonergan P., Evans A.C. (2012). Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiol. Genomics, 44: 799–810.Search in Google Scholar

Friedman E., Roth Z., Voet H., Lavon Y., Wolfenson D. (2012). Progesterone supplementation postinsemination improves fertility of cooled dairy cows during the summer. J. Dairy Sci., 95: 3092–3099.Search in Google Scholar

García-Ispierto I., López-Gatius F. (2012). Effects of GnRH or progesterone treatment on day 5 post-AI on plasma progesterone, luteal blood flow and leucocyte counts during the luteal phase in dairy cows. Reprod. Domest. Anim., 47: 224–229.Search in Google Scholar

García-Ispierto I., López-Gatius F. (2014). Effects of different five-day progesterone-based fixed-time AI protocols on follicular/luteal dynamics and fertility in dairy cows. J. Reprod. Dev., 60: 426–432.Search in Google Scholar

García-Ispierto I., López-Gatius F. (2017). Progesterone supplementation in the early luteal phase after artificial insemination improves conception rates in high-producing dairy cows. Theriogenology, 90: 20–24.Search in Google Scholar

García-Ispierto I., López-Helguera I., Serrano-Pérez B., Paso V., Tuono T., Ramon A., Mur-Novales R., Tutusaus J., López-Gatius F. (2016). Progesterone supplementation during the time of pregnancy recognition after artificial insemination improves conception rates in high-producing dairy cows. Theriogenology, 85: 1343–1347.Search in Google Scholar

Garrett J.E., Geisert R.D., Zavy M.T., Morgan G.L. (1988). Evidence for maternal regulation of early conceptus growth and development in beef cattle. J. Reprod. Fertil., 84: 437–446.Search in Google Scholar

Gifford C.A., Racicot K., Clark D.S., Austin K.J., Hansen T.R., Lucy M.C., Davies C.J., Ott T.L. (2007). Regulation of interferon-stimulated genes in peripheral blood leukocytes in pregnant and bred, nonpregnant dairy cows. J. Dairy Sci., 90: 274–280.Search in Google Scholar

Green J.C., Okamura C.S., Poock S.E., Lucy M.C. (2010). Measurement of interferon-tau (IFN-tau) stimulated gene expression in blood leukocytes for pregnancy diagnosis within 18–20d after insemination in dairy cattle. Anim. Reprod. Sci., 121: 24–33.Search in Google Scholar

Guillomot M., Fléchon J.E., Leroy F. (1993). Blastocyst development and implantation. In: Reproduction in mammals and man, Thibault C., Levasseur M.C., Hunter R.H.F. (eds). Paris, Ellipses, pp. 387–410.Search in Google Scholar

Han H., Austin K.J., Rempel L.A., Hansen T.R. (2006). Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows. J. Endocrinol., 191: 505–512.Search in Google Scholar

Hansen P.J. (2007). Hidden factors affecting fertility. WCDS Advances in Dairy Technology 19: 339–349.Search in Google Scholar

King G.J., Atkinson B.A., Robertson H.A. (1980). Development of the bovine placentome from days 20 to 29 of gestation. J. Reprod. Fertil., 59: 95–100.Search in Google Scholar

King G.J., Atkinson B.A., Robertson H.A. (1981). Development of the intercaruncular areas during early gestation and establishment of the bovine placenta. J. Reprod. Fertil., 61: 469–474.Search in Google Scholar

Klein C., Bauersachs S., Ulbrich S.E., Einspanier R., Meyer H.H., Schmidt S.E., Reichenbach H.D., Vermehren M., Sinowatz F., Blum H., Wolf E. (2006). Monozygotic twin model reveals novel embryo-induced transcriptome changes of bovine endometrium in the preattachment period. Biol. Reprod., 74: 253–264.Search in Google Scholar

Kose M., Kaya M.S., Aydilek N., Kucukaslan I., Bayril T., Bademkiran S., Kima Z., Ozyurtlu N., Kayis S.A., Guzeloglu A., Atli M.O. (2016). Expression profile of interferon tau-stimulated genes in ovine peripheral blood leukocytes during embryonic death. Theriogenology, 85: 1161–1166.Search in Google Scholar

Lonergan P., Forde N., Spencer T.E. (2016). Role of progesterone in embryo development in cattle. Reprod. Fertil. Dev., 28: 66–74.Search in Google Scholar

López-Gatius F. (2003). Is fertility declining in dairy cattle? A retrospective study in northeastern Spain. Theriogenology, 60: 89–99.Search in Google Scholar

López-Gatius F. (2012). Factors of a noninfectious nature affecting fertility after artificial insemination in lactating dairy cows. A review. Theriogenology, 77: 1029–1041.Search in Google Scholar

López-Gatius F., García-Ispierto I. (2010). Ultrasound and endocrine findings that help to assess the risk of late embryo/early foetal loss by non-infectious cause in dairy cattle. Reprod. Domest. Anim., 45: 15–24.Search in Google Scholar

López-Gatius F., Hunter R.H.F. (2017). From pre-ovulatory follicle palpation to the challenge of twin pregnancies: Clinical reflections following one million gynaecological examinations in dairy cows. Reprod. Domest. Anim., 52: 4–11.Search in Google Scholar

López-Gatius F., Labèrnia J., Santolaria P., López-Béjar M., Rutllant J. (1996). Effect of reproductive disorders previous to conception on pregnancy attrition in dairy cows, Theriogenology, 46: 643–648.10.1016/0093-691X(96)00215-4Search in Google Scholar

López-Gatius F., García-Ispierto I., Santolaria P., Yániz J., Nogareda C., López-Béjar M. (2006). Screening for high fertility in high-producing dairy cows. Theriogenology, 65: 1678–1689.Search in Google Scholar

López-Gatius F., Garbayo J.M., Santolaria P., Yániz J., Ayad A., de Sousa N.M., Beckers J.F. (2007). Milk production correlates negatively with plasma levels of pregnancy-associated glycoprotein (PAG) during the early foetal period in high producing dairy cows with live fetuses. Domest. Anim. Endocrinol., 32: 29–42.Search in Google Scholar

Lucy M.C. (2001). Reproductive loss in high-producing dairy cattle: where will it end? J. Dairy Sci., 84: 1277–1293.Search in Google Scholar

Manjari P., Reddi S., Alhussien M., Mohammed S., De S., Mohanty A.K., Sivalingam J., Dang A.K. (2016). Neutrophil gene dynamics and plasma cytokine levels in dairy cattle during peri-implantation period. Vet. Immunol. Immunopathol., 173: 44–49.Search in Google Scholar

Mann G.E., Lamming G.E. (2001). Relationship between maternal endocrine environment, early embryo development and inhibition of the luteolytic mechanism in cows. Reproduction, 121: 175–180.Search in Google Scholar

Mann G.E., Fray M.D., Lamming G.E. (2006). Effects of time of progesterone supplementation on embryo development and interferon-tau production in the cow. Vet J., 171: 500–503.Search in Google Scholar

Matsuyama S., Kojima T., Kato S., Kimura K. (2012). Relationship between quantity of IFNT estimated by IFN-stimulated gene expression in peripheral blood mononuclear cells and bovine embryonic mortality after AI or ET. Reprod. Biol. Endocrinol., 10: 21.Search in Google Scholar

Meyerholz M.M., Mense K., Knaack H., Sandra O., Schmicke M. (2016). Pregnancy-induced ISG-15 and MX-1 gene expression is detected in the liver of Holstein-Friesian heifers during late peri-implantation period. Reprod. Domest. Anim., 51: 175–177.Search in Google Scholar

Monteiro P.L. Jr., Ribeiro E.S., Maciel R.P., Dias A.L., Solé E. Jr., Lima F.S., Bisinotto R.S., Thatcher W.W., Sartori R., Santos J.E. (2014). Effects of supplemental progesterone after artificial insemination on expression of interferon-stimulated genes and fertility in dairy cows. J. Dairy Sci., 97: 4907–4921.Search in Google Scholar

Monteiro P.L. Jr., Nascimento A.B., Pontes G.C., Fernandes G.O., Melo L.F., Wiltbank M.C., Sartori R. (2015). Progesterone supplementation after ovulation: effects on corpus luteum function and on fertility of dairy cows subjected to AI or ET. Theriogenology, 84: 1215–1224.Search in Google Scholar

Paradis F., Yue S., Grant J.R., Stothard P., Basarab J.A., Fitzsimmons C. (2015). Transcriptomic analysis by RNA sequencing reveals that hepatic interferon-induced genes may be associated with feed efficiency in beef heifers. J. Anim. Sci., 93: 3331–3341.Search in Google Scholar

Parr M.H., Crowe M.A., Lonergan P., Evans A.C., Rizos D., Diskin M.G. (2014). Effect of exogenous progesterone supplementation in the early luteal phase post-insemination on pregnancy per artificial insemination in Holstein-Friesian cows. Anim. Reprod. Sci., 150: 7–14.Search in Google Scholar

Peter A.T., Beg M.A., Ahmad E., Bergfelt D.R. (2017). Trophoblast of domestic and companion animals: basic and applied clinical perspectives. Anim. Reprod., 14: 1209–1224.Search in Google Scholar

Pugliesi G., Miagawa B.T., Paiva Y.N., França M.R., Silva L.A., Binelli M. (2014). Conceptus-induced changes in the gene expression of blood immune cells and the ultrasound-accessed luteal function in beef cattle: how early can we detect pregnancy? Biol. Reprod., 91: 95.Search in Google Scholar

Ribeiro E.S., Bruno R.G., Farias A.M., Hernández-Rivera J.A., Gomes G.C., Surjus R., Becker L.F., Birt A., Ott T.L, Branen J.R., Sasser R.G., Keisler D.H., Thatcher W.W., Bilby T.R., Santos J.E. (2014). Low doses of bovine somatotropin enhance conceptus development and fertility in lactating dairy cows. Biol. Reprod., 90: 10.Search in Google Scholar

Ribeiro E.S., Gomes G., Greco L.F., Cerri R.L., Vieira-Neto A., Monteiro P.L. Jr., Lima F.S., Bisinotto R.S., Thatcher W.W., Santos J.E. (2016). Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows. J. Dairy Sci., 99: 2201–2220.Search in Google Scholar

Roberts R.M., Leaman D.W., Cross J.C. (1992). Role of interferons in maternal recognition of pregnancy in ruminants. Proc. Soc. Exp. Biol. Med., 200: 7–18.Search in Google Scholar

Ruhmann B., Giller K., Hankele A.K., Ulbrich S.E., Schmicke M. (2017). Interferon-τ induced gene expression in bovine hepatocytes during early pregnancy. Theriogenology, 104: 198–204.Search in Google Scholar

Serrano-Pérez B., Hansen P.J., Mur-Novales R., García-Ispierto I., de Sousa N.M., Beckers J.F., Almería S., López-Gatius F. (2016). Crosstalk between uterine serpin (SERPINA14) and pregnancy-associated glycoproteins at the foetal-maternal interface in pregnant dairy heifers experimentally infected with Neospora caninum. Theriogenology, 86: 824–830.Search in Google Scholar

Shirasuna K., Matsumoto H., Kobayashi E., Nitta A., Haneda S., Matsui M., Kawashima C., Kida K., Shimizu T., Miyamoto A. (2012). Upregulation of interferon-stimulated genes and interleukin-10 in peripheral blood immune cells during early pregnancy in dairy cows. J. Reprod. Dev., 58: 84–90.Search in Google Scholar

Spencer T.E., Johnson G.A., Bazer F.W., Burghardt R.C., Palmarini M. (2007). Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses. Reprod. Fert. Develop., 19: 65–78.Search in Google Scholar

Spencer T.E., Forde N., Lonergan P. (2016). The role of progesterone and conceptus-derived factors in uterine biology during early pregnancy in ruminants. J. Dairy Sci., 99: 5941–5950.Search in Google Scholar

Stevenson J.S., Portaluppi M.A., Tenhouse D.E., Lloyd A., Eborn D.R., Kacuba S., De Jarnette J.M. (2007). Interventions after artificial insemination: conception rates, pregnancy survival, and ovarian responses to gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone. J. Dairy Sci., 90: 331–340.Search in Google Scholar

Wijma R., Stangaferro M.L., Kamat M.M., Vasudevan S., Ott T.L., Giordano J.O. (2016). Embryo mortality around the period of maintenance of the corpus luteum causes alterations to the ovarian function of lactating dairy cows. Biol. Reprod., 95: 112.Search in Google Scholar

Yan L., Robinson R., Shi Z., Mann G. (2016). Efficacy of progesterone supplementation during early pregnancy in cows: a meta-analysis. Theriogenology, 85: 1390–1398.Search in Google Scholar

Yuan J.S., Reed A., Chen F., Stewart C.N. Jr. (2006). Statistical analysis of real-time PCR data. BMC Bioinformatics, 7: 85.Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo