Genetic Expression of Progesterone and Oxytocin Receptors in Kari Sheep during Estrus and Early Pregnancy
DOI:
https://doi.org/10.70749/ijbr.v3i8.2087Keywords:
Genes Expression, Sheep, Estrus Cycle, Pregnancy, P4, OXTR, GABDH.Abstract
Kari is a small breed of sheep found in Chitral district of Khyber Pakhtunkhwa with unique characteristics having shorter gestation length than other breeds i.e. lesser than five months. In this experiment the expression pattern of oxytocin and progesterone receptors gene in estrus cycle and early pregnancy was studied. For this experiment total seven ewes non-pregnant scanned through ultrasonography and then estrous synchronized with double PGF2α protocol. The fertile rams were allowed, and mating was observed. Blood samples was collected from ewes before and after confirmation of pregnancy. RNA was isolated from the blood and synthesized c-DNA through RT-PCR. The c-DNA was amplified using primers i.e. P4, OXTR and GABDH. No expression of OXTR was observed between 08th and 12th day in control, non-pregnant and pregnant ewes while expression of OXTR was observed on 14th day in non-pregnant and no expression in pregnant ewes. The expression of progesterone receptors was high on 10th and 12th day in pregnant ewes while low level was recorded on 16th day. In control and non-pregnant ewes the expression of P4 mRNA was lower at 08th day and highly expressed on 14th and 16th day of estrus cycle. It is concluded that early pregnancy in ewes sustained by a complex interplay between the conceptus and endometrium. This contact involves factors like IFN-t, progesterone, and growth factors, which regulate gene expression to suppress luteolysis and maintain pregnancy.
Downloads
References
Ahmad, S., Khan, R., Habib, G., & Siddiqui, M. (2002). The" Kari sheepA genetic heritage'. The Journal of Animal and Plant Sciences (Pakistan), 12(1).
https://agris.fao.org/search/en/providers/122650/records/64723e472c1d629bc978e615
An, S., Kim, S. S., Kim, J., Park, M., Lee, J., Cho, S. K., Lee, K., & An, B. (2017). Expression of reproductive hormone receptors and contraction-associated genes in porcine uterus during the estrous cycle. Molecular Medicine Reports, 15(6), 4176-4184.
https://doi.org/10.3892/mmr.2017.6518
ARONICA, S. M., & KATZENELLENBOGEN, B. S. (1991). Progesterone receptor regulation in uterine Cells:Stimulation by estrogen, cyclic adenosine 3′,5′-Monophosphate, and insulin-like growth factor I andSuppression by Antiestrogens and protein KinaseInhibitors*. Endocrinology, 128(4), 2045-2052.
https://doi.org/10.1210/endo-128-4-2045
Bazer, F. W., Song, G., & Thatcher, W. W. (2011). Roles of conceptus secretory proteins in establishment and maintenance of pregnancy in ruminants. Asian-Australasian Journal of Animal Sciences, 25(1), 1-16.
https://doi.org/10.5713/ajas.2011.r.08
Bazer, F. W. (2011). Uterine receptivity to implantation of blastocysts in mammals. Frontiers in Bioscience, S3(2), 745-767.
Bazer, F. W., Ott, T. L., & Spencer, T. E. (1994). Pregnancy recognition in ruminants, pigs and horses: Signals from the trophoblast. Theriogenology, 41(1), 79-94.
https://doi.org/10.1016/s0093-691x(05)80052-4
Bazer, F., Thatcher, W., Hansen, P., Mirando, M., Ott, T., & Plante, C. (2019). Physiological mechanisms of pregnancy recognition in ruminants. Bioscientifica Proceedings.
https://doi.org/10.1530/biosciprocs.2.004
Bazer, F. (1989). Establishment of pregnancy in sheep and pigs. Reproduction, Fertility and Development, 1(3), 237.
https://doi.org/10.1071/rd9890237
Bigsby, R. M. (1991). Reciprocal tissue interactions in morphogenesis and hormonal responsiveness of the female reproductive tract. Cellular Signals Controlling Uterine Function, 11-29.
https://doi.org/10.1007/978-1-4615-3724-3_3
Bouvier, C., Lagacé, G., & Collu, R. (1991). G protein modulation by estrogens. Molecular and Cellular Endocrinology, 79(1-3), 65-73.
https://doi.org/10.1016/0303-7207(91)90096-b
Chami, O., Megevand, A., Ott, T., Bazer, F., & O’Neill, C. (1999). Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF2α release. American Journal of Physiology-Endocrinology and Metabolism, 276(4), E783-E792.
https://doi.org/10.1152/ajpendo.1999.276.4.e783
Chauchereau, A., Savouret, J., & Milgrom, E. (1992). Control of biosynthesis and post-transcriptional modification of the progesterone receptor. Biology of Reproduction, 46(2), 174-177.
https://doi.org/10.1095/biolreprod46.2.174
Cherny, R., Salamonsen, L., & Findlay, J. (1991). Immunocytochemical localization of oestrogen receptors in the endometrium of the Ewe. Reproduction, Fertility and Development, 3(3), 321.
https://doi.org/10.1071/rd9910321
Clarke, C. L. (1990). Cell-specific regulation of progesterone receptor in the female reproductive system. Molecular and Cellular Endocrinology, 70(3), C29-C33.
https://doi.org/10.1016/0303-7207(90)90210-y
Farin, C. E., Imakawa, K., Hansen, T. R., McDonnell, J. J., Murphy, C. N., Farin, P. W., & Roberts, R. M. (1990). Expression of trophoblastic interferon genes in sheep and Cattle1. Biology of Reproduction, 43(2), 210-218.
https://doi.org/10.1095/biolreprod43.2.210
Feng, H., Bhave, M., & Fairclough, R. (2000). Regulation of oxytocin receptor gene expression in sheep: Tissue specificity, multiple transcripts and mRNA editing. Reproduction, 120(1), 187-200.
https://doi.org/10.1530/reprod/120.1.187
Fleming, J. G., Spencer, T. E., Safe, S. H., & Bazer, F. W. (2006). Estrogen regulates transcription of the ovine oxytocin receptor gene through GC-rich SP1 promoter elements. Endocrinology, 147(2), 899-911.
https://doi.org/10.1210/en.2005-1120
Flint, A. P. F., Lamming, G. E., Stewart, H. J., & Abayasekara, D. R. E. (1994). The role of the endometrial oxytocin receptor in determining the length of the sterile oestrous cycle and ensuring maintenance of luteal function in early pregnancy in ruminants. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 344(1309), 291-304.
https://doi.org/10.1098/rstb.1994.0067
Flint, A. P., Stewart, H. J., Lamming, G. E., & Payne, J. H. (1992). Role of the oxytocin receptor in the choice between cyclicity and gestation in ruminants. Journal of reproduction and fertility. Supplement, 45, 53-58.
https://europepmc.org/article/med/1338956
Flint, A. P., Leat, W. M., Sheldrick, E. L., & Stewart, H. J. (1986). Stimulation of phosphoinositide hydrolysis by oxytocin and the mechanism by which oxytocin controls prostaglandin synthesis in the ovine endometrium. Biochemical Journal, 237(3), 797-805.
https://doi.org/10.1042/bj2370797
Flint, A. P., & Sheldrick, E. L. (1986). Ovarian oxytocin and the maternal recognition of pregnancy. Reproduction, 76(2), 831-839.
https://doi.org/10.1530/jrf.0.0760831
FUCHS, A., FUCHS, F., HUSSLEIN, P., SOLOFF, M. S., & FERNSTROM, M. J. (1982). Oxytocin receptors and human parturition. Obstetrical & Gynecological Survey, 37(9), 567-568.
https://doi.org/10.1097/00006254-198209000-00002
Geisert, R. D., & Malayer, J. R. (2000). Implantation. In" Reproduction in Farm Animals"(B. Hafez and ESE Hafez, Eds.).
Gimenez, D., & Rodning, S. (2007). Reproductive management of sheep and goats. ANR (Auburn, Ala.).
Hartt, L. S., Carling, S. J., Joyce, M. M., Johnson, G. A., Vanderwall, D. K., & Ott, T. L. (2005). Temporal and spatial associations of oestrogen receptor Alpha and progesterone receptor in the endometrium of cyclic and early pregnant Mares. Reproduction, 130(2), 241-250.
https://doi.org/10.1530/rep.1.00596
Hixon, J. E., & Flint, A. P. (1987). Effects of a luteolytic dose of oestradiol benzoate on uterine oxytocin receptor concentrations, phosphoinositide turnover and prostaglandin F-2 secretion in sheep. Reproduction, 79(2), 457-467.
https://doi.org/10.1530/jrf.0.0790457
Imakawa, K., Helmer, S. D., Nephew, K. P., Meka, C. S., & Christenson, R. K. (1993). A novel role for GM-CSF: Enhancement of pregnancy specific interferon production, ovine trophoblast protein-1. Endocrinology, 132(4), 1869-1871.
https://doi.org/10.1210/endo.132.4.7681767
Jainudeen, M., & Hafez, E. (2000). Gestation, prenatal physiology, and parturition. Reproduction in Farm Animals, 140 155.
https://doi.org/10.1002/9781119265306.ch10
Koji, T., Chedid, M., Rubin, J. S., Slayden, O. D., Csaky, K. G., Aaronson, S. A., & Brenner, R. M. (1994). Progesterone-dependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: Keratinocyte growth factor as a progestomedin. The Journal of cell biology, 125(2), 393-401.
https://doi.org/10.1083/jcb.125.2.393
KOLIGIAN, K. B., & STORMSHAK, F. (1977). Nuclear and cytoplasmic estrogen receptors in ovine endometrium during the estrous cycle. Endocrinology, 101(2), 524-533.
https://doi.org/10.1210/endo-101-2-524
Lamming, G. E., Wathes, D. C., Flint, A. P., Payne, J. H., Stevenson, K. R., & Vallet, J. L. (1995). Local action of trophoblast interferons in suppression of the development of oxytocin and oestradiol receptors in ovine endometrium. Reproduction, 105(1), 165-175.
https://doi.org/10.1530/jrf.0.1050165
Leavitt, W., Okulicz, W., Mccracken, J., Schramm, W., & Robidoux, W. (1985). Rapid recovery of nuclear estrogen receptor and oxytocin receptor in the ovine uterus following progesterone withdrawal. Journal of Steroid Biochemistry, 22(6), 687-691.
https://doi.org/10.1016/0022-4731(85)90272-9
LEAVITT, W. W., TOFT, D. O., STROTT, C. A., & O′MALLEY, B. W. (1974). A specific progesterone receptor in the hamster uterus: physiologic properties and regulation during the estrous cycle. Endocrinology, 94(4), 1041-1053.
https://doi.org/10.1210/endo-94-4-1041
Mann. G. E, G. E. Lamming, R. S. Robinson and D.C. Wathes. 1999. The regulation of interferon production and uterine hormone receptors during early pregnancy in the cow. J. Reprod. and Ferti. Suppl. 54, 317–328
McCracken, J., Schramm, W., & Okulicz, W. (1984). Hormone receptor control of pulsatile secretion of PGF2α from the ovine uterus during luteolysis and its abrogation in early pregnancy. Animal Reproduction Science, 7(1-3), 31-55.
https://doi.org/10.1016/0378-4320(84)90027-7
McCracken. J. A. 1980. Hormone receptor control of prostaglandin secretion by the ovine uterus. In Advances in Prostaglandin and Thromboxane Research. Eds B. Samaelsson and P. W. Ramwell. New York: Raven Press.
McCRACKEN, J. A., CARLSON, J. C., GLEW, M. E., GODING, J. R., BAIRD, D. T., GREEN, K., & SAMUELSSON, B. (1972). Prostaglandin F2α identified as a Luteolytic hormone in sheep. Nature New Biology, 238(83), 129-134.
https://doi.org/10.1038/newbio238129a0
MILGROM, E., ATGER, M., PERROT, M., & BAULIEU, E. -. (1972). Progesterone in uterus and plasma: VI. Uterine progesterone receptors during the Estrus cycle and implantation in the Guinea pig. Endocrinology, 90(4), 1071-1078.
https://doi.org/10.1210/endo-90-4-1071
Mirando, M. A., Harney, J. P., Zhou, Y., Ogle, T. F., Ott, T. L., Moffatt, R. J., & Bazer, F. W. (1993). Changes in progesterone and oestrogen receptor mRNA and protein and oxytocin receptors in endometrium of ewes after intrauterine injection of ovine trophoblast interferon. Journal of Molecular Endocrinology, 10(2), 185-192.
https://doi.org/10.1677/jme.0.0100185
Ndiaye, K., Poole, D. H., & Pate, J. L. (2008). Expression and regulation of functional oxytocin receptors in bovine T Lymphocytes1. Biology of Reproduction, 78(4), 786-793.
https://doi.org/10.1095/biolreprod.107.065938
Ott, T. L., Zhou, Y., Mirando, M. A., Stevens, C., Harney, J. P., Ogle, T. F., & Bazer, F. W. (1993). Changes in progesterone and oestrogen receptor mRNA and protein during maternal recognition of pregnancy and luteolysis in ewes. Journal of Molecular Endocrinology, 10(2), 171-183.
https://doi.org/10.1677/jme.0.0100171
Ott, T. L., Mirando, M. A., Davis, M. A., & Bazer, F. W. (1992). Effects of ovine conceptus secretory proteins and progesterone on oxytocin-stimulated endometrial production of prostaglandin and turnover of inositol phosphate in ovariectomized ewes. Reproduction, 95(1), 19-29.
https://doi.org/10.1530/jrf.0.0950019
Ottobre, J. S., Lewis, G. S., Thayne, W. V., & Inskeep, E. K. (1980). Mechanism by which progesterone shortens the Estrous cycle of the Ewe. Biology of Reproduction, 23(5), 1046-1053.
https://doi.org/10.1095/biolreprod23.5.1046
Rahman, A. N. (1970). Hormonal changes in the uterus during pregnancy - Lessons from the Ewe: A review. Journal of Agriculture & Rural Development, 4(1), 1-7.
https://doi.org/10.3329/jard.v4i1.761
Riaz, H., Sattar, A., Arshad, M., & Ahmad, N. (2012). Effect of synchronization protocols and GnRH treatment on the reproductive performance in goats. Small Ruminant Research, 104(1-3), 151-155.
https://doi.org/10.1016/j.smallrumres.2011.10.008
Robinson, R., Mann, G., Lamming, G., & Wathes, D. (2001). Expression of oxytocin, oestrogen and progesterone receptors in uterine biopsy samples throughout the oestrous cycle and early pregnancy in cows. Reproduction, 122(6), 965-979.
https://doi.org/10.1530/rep.0.1220965
Salamonsen, L., & Findlay, J. (1990). Immunocytochemical localization of prostaglandin synthase in the ovine uterus during the oestrous cycle and in early pregnancy. Reproduction, Fertility and Development, 2(4), 311.
https://doi.org/10.1071/rd9900311
Satterfield, M. C., Bazer, F. W., & Spencer, T. E. (2006). Progesterone regulation of Preimplantation conceptus growth and Galectin 15 (LGALS15) in the ovine Uterus1. Biology of Reproduction, 75(2), 289-296.
https://doi.org/10.1095/biolreprod.106.052944
Savouret, J., Bailly, A., Misrahi, M., Rauch, C., Redeuilh, G., Chauchereau, A., & Milgrom, E. (1991). Characterization of the hormone responsive element involved in the regulation of the progesterone receptor gene. The EMBO Journal, 10(7), 1875-1883.
https://doi.org/10.1002/j.1460-2075.1991.tb07713.x
Sheldrick, E. L., & Flint, A. P. (1985). Endocrine control of uterine oxytocin receptors in the Ewe. Journal of Endocrinology, 106(2), 249-258.
https://doi.org/10.1677/joe.0.1060249
Sheldrick, E. L., & Flint, A. P. (1983). Luteal concentrations of oxytocin decline during early pregnancy in the Ewe. Reproduction, 68(2), 477-480.
https://doi.org/10.1530/jrf.0.0680477
Soede, N., Langendijk, P., & Kemp, B. (2011). Reproductive cycles in pigs. Animal Reproduction Science, 124(3-4), 251-258.
https://doi.org/10.1016/j.anireprosci.2011.02.025
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. Reproduction, Fertility and Development, 19(1), 65.
https://doi.org/10.1071/rd06102
Spencer, T. E., & Bazer, F. W. (2004). Conceptus signals for establishment and maintenance of pregnancy. Reproductive Biology and Endocrinology, 2(1).
https://doi.org/10.1186/1477-7827-2-49
Spencer, T., Mirando, M., Mayes, J., Watson, G., Ott, T., & Bazer, F. (1996). Effects of interferon-tau and progesterone on oestrogen-stimulated expression of receptors for oestrogen, progesterone and oxytocin in the endometrium of ovariectomized ewes. Reproduction, Fertility and Development, 8(5), 843.
https://doi.org/10.1071/rd9960843
Spencer, T. E., & Bazer, F. W. (1995). Temporal and spatial alterations in uterine estrogen receptor and progesterone receptor gene expression during the Estrous cycle and early pregnancy in the Ewe1. Biology of Reproduction, 53(6), 1527-1543.
https://doi.org/10.1095/biolreprod53.6.1527
Stewart, H., McCann, S., Northrop, A., Lamming, G., & Flint, A. (1989). Sheep antiluteolytic interferon: CDNA sequence and analysis of mRNA levels. Journal of Molecular Endocrinology, 2(1), 65-70.
https://doi.org/10.1677/jme.0.0020065
Thatcher, W., Meyer, M., & Danet-Desnoyers, G. (2019). Maternal recognition of pregnancy. Bioscientifica Proceedings.
https://doi.org/10.1530/biosciprocs.3.002
Warren, J. E., Hawk, H. W., & Bolt, D. J. (1973). Evidence for Progestational priming of estradiol-induced luteal regression in the Ewe1. Biology of Reproduction, 8(4), 435-440.
https://doi.org/10.1093/biolreprod/8.4.435
Wathes, D., & Lamming, G. (2019). The oxytocin receptor, luteolysis and the maintenance of pregnancy. Bioscientifica Proceedings.
https://doi.org/10.1530/biosciprocs.3.005
Wathes, D. C., Gilbert, C. L., & Ayad, V. J. (1993). Interactions between Oxytocin, the Ovaries, and the Reproductive Tract in the Regulation of Fertility in the Ewe a. Annals of the New York Academy of Sciences, 689(1), 396-410.
https://doi.org/10.1111/j.1749-6632.1993.tb55563.x
Wathes, D. C., & Hamon, M. (1993). Localization of oestradiol, progesterone and oxytocin receptors in the uterus during the oestrous cycle and early pregnancy of the Ewe. Journal of Endocrinology, 138(3), 479-NP.
https://doi.org/10.1677/joe.0.1380479
Wathes. D. C. 1989. Oxytocin and vasopressin in the gonads. In Oxford Reviews of Reprod. Biol. vol. 11, pp. 226-283. Ed. S. R. Milligan, Oxford, New York, Tokyo: Oxford University Press.
Xiao, C. W., & Goff, A. K. (1999). Hormonal regulation of oestrogen and progesterone receptors in cultured bovine endometrial cells. Reproduction, 115(1), 101-109.
https://doi.org/10.1530/jrf.0.1150101
Yang, L., Yao, X., Li, S., Chen, K., Wang, Y., Chen, L., & Zhang, L. (2016). Expression of genes associated with luteolysis in peripheral blood mononuclear cells during early pregnancy in cattle. Molecular Reproduction and Development, 83(6), 509-515.
https://doi.org/10.1002/mrd.22647
Yang, Q., Gu, Y., Zhang, X., Wang, J., He, Y., Shi, Y., Sun, Z., Shi, H., & Wang, J. (2016). Uterine expression of NDRG4 is induced by estrogen and up-regulated during embryo implantation process in mice. PLOS ONE, 11(5), e0155491.
https://doi.org/10.1371/journal.pone.0155491
Zelinski, M. B., Hirota, N. A., Keenan, E. J., & Stormshak, F. (1980). Influence of exogenous estradiol-17β on endometrial progesterone and estrogen receptors during the luteal phase of the ovine Estrous Cycle1. Biology of Reproduction, 23(4), 743-751.
https://doi.org/10.1095/biolreprod23.4.743
Zhang, J., Weston, P. G., & Hixon, J. E. (1992). Role of progesterone and oestradiol in the regulation of uterine oxytocin receptors in ewes. Reproduction, 94(2), 395-404.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research
This work is licensed under a Creative Commons Attribution 4.0 International License.
