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Abstract
Mucin-1 (MUC-1) is an anti-adhesion glycoprotein expressed on the apical surface of the endometrial luminal and glandular epithelium which prevents interactions between the trophectoderm and endometrial epithelium. The aim of this study was to investigate the outcome of PG-600 on ovine endometrial MUC-1 immunoexpression during early and mid-diestrus. Twenty-four cycling ewes (Polypay) were administered progesterone for 9 days. Two days before progesterone withdrawal, ewes were treated with cloprostenol. At progesterone withdrawal (d0), ewes were treated with either PG-600 (5 mL) or saline (5 mL) group. Endometrial tissues were collected surgically on days 4 and 7 after PG-600 or saline (n=6/group/timepoint) and were subjected to immunohistochemistry followed by image acquisition. Stained area for MUC-1 was quantified using Image J. The diestrous intercaruncular endometrium of both treated and control ewes expressed MUC-1. However, the percent area expressing MUC-1 varied between endometrial area (luminal and superficial glandular epithelium), time (day four, day 7), and treatment group. PG-600 treatment increased MUC-1 expression in the luminal epithelium on day 7 and in the superficial glandular epithelium expression on day 4. The results of this study show that administration of PG-600 to ewes increases endometrial MUC-1 expression in mid diestrus, which provides a possible mechanism for lower fertility found following treatment by PG-600 in sheep.
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References
- Aplin, J. D. (1997). Adhesion molecules in implantation. Reviews of Reproduction, 2(2), 84–93. https://doi.org/10.1530/ROR.0.0020084
- Bartlewski, P. M., Beard, A. P., & Rawlings, N. C. (1999). Ovarian function in ewes at the onset of the breeding season. Animal Reproduction Science, 57(1–2), 67–88. https://doi.org/10.1016/S0378-4320(99)00060-3
- Bowen, J. A., Bazer, F. W., & Burghardt, R. C. (1996). Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo. Biology of Reproduction, 55(5), 1098–1106. https://doi.org/10.1095/biolreprod55.5.1098
- Brayman, M., Thathiah, A., & Carson, D. D. (2004). MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reproductive Biology and Endocrinology, 2(4), 1-9. https://doi.org/10.1186/1477-7827-2-4
- Carson, D. D., Bagchi, I., Dey, S. K., Enders, A. C., Fazleabas, A. T., Lessey, B. A., & Yoshinaga, K. (2000). Embryo implantation. Developmental Biology, 223(2), 217-237. https://doi.org/10.1006/dbio.2000.9767
- Cross, L. J., Cross, R. M., & Stormshak, F. (2019). Optimal dose of PG600 when given to progestogen-synchronized ewes during anestrus as affected by day of the year and temperature1. Translational Animal Science, 3(1), 433-442. https://doi.org/10.1093/tas/txy092
- D’Souza, K. N., Rastle-Simpson, S. L., Redhead, A. K., Baptiste, Q. S., Smith, B., & Knights, M. (2014). Gonadotropin stimulation using P.G. 600?? on reproductive success of non-lactating anestrous ewes. Animal Reproduction Science, 148(3–4), 115–120. https://doi.org/10.1016/j.anireprosci.2014.05.001
- Dharmaraj, N., Gendler, S. J., & Carson, D. D. (2009). Expression of Human MUC1 During Early Pregnancy in the Human MUC1 Transgenic Mouse Model1. Biology of Reproduction, 81(6), 1182–1188. https://doi.org/10.1095/biolreprod.109.079418
- Guillomot, M., Fléchon, J. E., & Wintenberger-Torres S. (1981). Conceptus attachment in the ewe: an ultrastructural study. Placenta. 2(2):169-82. https://doi.org/10.1016/s0143-4004(81)80021-5
- Habeeb, H., Hazzard, T., Stormshak, F., & Kutzler, M. (2020). Ovulation, pregnancy, and lambing rates during nonbreeding season with or without exogenous gonadotropin stimulation. Clinical Theriogenology, 12(1), 23–28.
- Habeeb, H. M. H., Hazzard, T. M., Stormshak, F., & Kutzler, M. A. (2019). Effect of different dosages of PG-600 on ovulation and pregnancy rates in ewes during the breeding season. Translational Animal Science, 3(1), 429–432. https://doi.org/10.1093/tas/txy112
- Habeeb, H. M. H., Kleditz, L., Hazzard, T., Bishop, C., Stormshak, F., & Kutzler, M. A. (2023). Ovine endometrial estrogen receptor expression is altered following PG-600 administration. Veterinary Medicine and Science, 9(3), 1379–1384. https://doi.org/10.1002/vms3.1119
- Hild-Petito, S., Fazleabas, A. T., Julian, J., & Carson, D. D. (1996). Mucin (Muc-1) expression is differentially regulated in uterine luminal and glandular epithelia of the baboon (Papio anubis). Biology of Reproduction, 54(5), 939–947. https://doi.org/10.1095/BIOLREPROD54.5.939
- Johnson, G. A., Bazer, F. W., Jaeger, L. A., Ka, H., Garlow, J. E., Pfarrer, C., Spencer, T. C., & Burghardt, R. C. (2001). Muc-1, integrin, and osteopontin expression during the implantation cascade in sheep. Biology of Reproduction, 65(3), 820–828. https://doi.org/10.1095/biolreprod65.3.820
- Jonckheere, N., Vincent, A., Neve, B., Van Seuningen, I. (2021). Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers, Biochimica et Biophysica Acta - Reviews on Cancer, 1876, (1),188538, https://doi.org/10.1016/j.bbcan.2021.188538
- Margarit, L., Taylor, A., Roberts, M. H., Hopkins, L., Davies, C., Brenton, A. G., Conlan, R. S., Bunkheila, A., Joels, L., White, J. O., & Gonzalez, D. (2010). MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. The Journal of Clinical Endocrinology and Metabolism, 95(12), 5320–5329. https://doi.org/10.1210/JC.2010-0603
- Raheem, K. A., Marei, W. F. A., Campbell, B. K., & Fouladi-Nashta, A. A. (2016). In vivo and in vitro studies of MUC1 regulation in sheep endometrium. Theriogenology, 85(9), 1635-1643.https://doi.org/10.1016/j.theriogenology.2016.01.018
- Ren, Q., Guan, S., Fu, J., & Wang, A. (2010). Temporal and spatial expression of Muc1 during implantation in sows. International Journal of Molicular Sciences, 27(6):2322-2335. https://www.mdpi.com/1422-0067/11/6/2322
- Song, G., Kim, J., Dunlap, K. A., Satterfield, M. C., Johnson, G. A., Burghardt, R. C., & Wu, G. (2012). Uterine biology in pigs and sheep. Journal of Animal Science and Biotechnology, 3(23), 1-21 https://doi.org/10.1186/2049-1891-3-23
- Surveyor, G. A., Gendler, S. J., Pemberton, L., Das, S. K., Chakraborty, I., Julian, J., Pimental, R. A., Wegner, C. C., Dey, S. K., & Carson, D. D. (1995). Expression and steroid hormonal control of Muc-1 in the mouse uterus. Endocrinology, 136(8), 3639–3647. https://doi.org/10.1210/EN.136.8.3639
- Tabak, L. A. (2010). The role of mucin-type O-glycans in eukaryotic development. Seminars in Cell & Developmental Biology, 21(6), 616–621. https://doi.org/10.1016/J.SEMCDB.2010.02.001
- Tisdall, D. J., Watanabe, K., Hudson, N. L., Smith, P., & McNatty, K. P. (1995). FSH receptor gene expression during ovarian follicle development in sheep. Journal of Molecular Endocrinology, 15(3), 273–281. https://doi.org/10.1677/jme.0.0150273
- Umberger, S. H., Jabbar, G., & Lewis, G. S. (1994). Seasonally anovulatory ewes fail to respond to progestogen treatment in the absence of gonadotropin stimulation. Theriogenology, 42(8), 1329–1336. https://doi.org/10.1016/0093-691X(94)90253-F
- Wang, X., Zhu, B., Xiong, S., Sheng, X., Qi, X., Huang, Q., Chen, C., Guo, Y., & Ni, H. (2018). Expression and function of MUC1 in uterine tissues during early pregnancy in sheep after natural oestrous or artificially-induced oestrous. Theriogenology, 108, 339–347. https://doi.org/10.1016/j.theriogenology.2017.12.030
- Wu, F., Chen, X., Liu, Y., Liang, B., Xu, H., Li, T. C., & Wang, C. C. (2018). Decreased MUC1 in endometrium is an independent receptivity marker in recurrent implantation failure during implantation window. Reproductive Biology and Endocrinology, 16(1), 1–7. https://doi.org/10.1186/s12958-018-0379-1
References
Aplin, J. D. (1997). Adhesion molecules in implantation. Reviews of Reproduction, 2(2), 84–93. https://doi.org/10.1530/ROR.0.0020084
Bartlewski, P. M., Beard, A. P., & Rawlings, N. C. (1999). Ovarian function in ewes at the onset of the breeding season. Animal Reproduction Science, 57(1–2), 67–88. https://doi.org/10.1016/S0378-4320(99)00060-3
Bowen, J. A., Bazer, F. W., & Burghardt, R. C. (1996). Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vivo. Biology of Reproduction, 55(5), 1098–1106. https://doi.org/10.1095/biolreprod55.5.1098
Brayman, M., Thathiah, A., & Carson, D. D. (2004). MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reproductive Biology and Endocrinology, 2(4), 1-9. https://doi.org/10.1186/1477-7827-2-4
Carson, D. D., Bagchi, I., Dey, S. K., Enders, A. C., Fazleabas, A. T., Lessey, B. A., & Yoshinaga, K. (2000). Embryo implantation. Developmental Biology, 223(2), 217-237. https://doi.org/10.1006/dbio.2000.9767
Cross, L. J., Cross, R. M., & Stormshak, F. (2019). Optimal dose of PG600 when given to progestogen-synchronized ewes during anestrus as affected by day of the year and temperature1. Translational Animal Science, 3(1), 433-442. https://doi.org/10.1093/tas/txy092
D’Souza, K. N., Rastle-Simpson, S. L., Redhead, A. K., Baptiste, Q. S., Smith, B., & Knights, M. (2014). Gonadotropin stimulation using P.G. 600?? on reproductive success of non-lactating anestrous ewes. Animal Reproduction Science, 148(3–4), 115–120. https://doi.org/10.1016/j.anireprosci.2014.05.001
Dharmaraj, N., Gendler, S. J., & Carson, D. D. (2009). Expression of Human MUC1 During Early Pregnancy in the Human MUC1 Transgenic Mouse Model1. Biology of Reproduction, 81(6), 1182–1188. https://doi.org/10.1095/biolreprod.109.079418
Guillomot, M., Fléchon, J. E., & Wintenberger-Torres S. (1981). Conceptus attachment in the ewe: an ultrastructural study. Placenta. 2(2):169-82. https://doi.org/10.1016/s0143-4004(81)80021-5
Habeeb, H., Hazzard, T., Stormshak, F., & Kutzler, M. (2020). Ovulation, pregnancy, and lambing rates during nonbreeding season with or without exogenous gonadotropin stimulation. Clinical Theriogenology, 12(1), 23–28.
Habeeb, H. M. H., Hazzard, T. M., Stormshak, F., & Kutzler, M. A. (2019). Effect of different dosages of PG-600 on ovulation and pregnancy rates in ewes during the breeding season. Translational Animal Science, 3(1), 429–432. https://doi.org/10.1093/tas/txy112
Habeeb, H. M. H., Kleditz, L., Hazzard, T., Bishop, C., Stormshak, F., & Kutzler, M. A. (2023). Ovine endometrial estrogen receptor expression is altered following PG-600 administration. Veterinary Medicine and Science, 9(3), 1379–1384. https://doi.org/10.1002/vms3.1119
Hild-Petito, S., Fazleabas, A. T., Julian, J., & Carson, D. D. (1996). Mucin (Muc-1) expression is differentially regulated in uterine luminal and glandular epithelia of the baboon (Papio anubis). Biology of Reproduction, 54(5), 939–947. https://doi.org/10.1095/BIOLREPROD54.5.939
Johnson, G. A., Bazer, F. W., Jaeger, L. A., Ka, H., Garlow, J. E., Pfarrer, C., Spencer, T. C., & Burghardt, R. C. (2001). Muc-1, integrin, and osteopontin expression during the implantation cascade in sheep. Biology of Reproduction, 65(3), 820–828. https://doi.org/10.1095/biolreprod65.3.820
Jonckheere, N., Vincent, A., Neve, B., Van Seuningen, I. (2021). Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers, Biochimica et Biophysica Acta - Reviews on Cancer, 1876, (1),188538, https://doi.org/10.1016/j.bbcan.2021.188538
Margarit, L., Taylor, A., Roberts, M. H., Hopkins, L., Davies, C., Brenton, A. G., Conlan, R. S., Bunkheila, A., Joels, L., White, J. O., & Gonzalez, D. (2010). MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. The Journal of Clinical Endocrinology and Metabolism, 95(12), 5320–5329. https://doi.org/10.1210/JC.2010-0603
Raheem, K. A., Marei, W. F. A., Campbell, B. K., & Fouladi-Nashta, A. A. (2016). In vivo and in vitro studies of MUC1 regulation in sheep endometrium. Theriogenology, 85(9), 1635-1643.https://doi.org/10.1016/j.theriogenology.2016.01.018
Ren, Q., Guan, S., Fu, J., & Wang, A. (2010). Temporal and spatial expression of Muc1 during implantation in sows. International Journal of Molicular Sciences, 27(6):2322-2335. https://www.mdpi.com/1422-0067/11/6/2322
Song, G., Kim, J., Dunlap, K. A., Satterfield, M. C., Johnson, G. A., Burghardt, R. C., & Wu, G. (2012). Uterine biology in pigs and sheep. Journal of Animal Science and Biotechnology, 3(23), 1-21 https://doi.org/10.1186/2049-1891-3-23
Surveyor, G. A., Gendler, S. J., Pemberton, L., Das, S. K., Chakraborty, I., Julian, J., Pimental, R. A., Wegner, C. C., Dey, S. K., & Carson, D. D. (1995). Expression and steroid hormonal control of Muc-1 in the mouse uterus. Endocrinology, 136(8), 3639–3647. https://doi.org/10.1210/EN.136.8.3639
Tabak, L. A. (2010). The role of mucin-type O-glycans in eukaryotic development. Seminars in Cell & Developmental Biology, 21(6), 616–621. https://doi.org/10.1016/J.SEMCDB.2010.02.001
Tisdall, D. J., Watanabe, K., Hudson, N. L., Smith, P., & McNatty, K. P. (1995). FSH receptor gene expression during ovarian follicle development in sheep. Journal of Molecular Endocrinology, 15(3), 273–281. https://doi.org/10.1677/jme.0.0150273
Umberger, S. H., Jabbar, G., & Lewis, G. S. (1994). Seasonally anovulatory ewes fail to respond to progestogen treatment in the absence of gonadotropin stimulation. Theriogenology, 42(8), 1329–1336. https://doi.org/10.1016/0093-691X(94)90253-F
Wang, X., Zhu, B., Xiong, S., Sheng, X., Qi, X., Huang, Q., Chen, C., Guo, Y., & Ni, H. (2018). Expression and function of MUC1 in uterine tissues during early pregnancy in sheep after natural oestrous or artificially-induced oestrous. Theriogenology, 108, 339–347. https://doi.org/10.1016/j.theriogenology.2017.12.030
Wu, F., Chen, X., Liu, Y., Liang, B., Xu, H., Li, T. C., & Wang, C. C. (2018). Decreased MUC1 in endometrium is an independent receptivity marker in recurrent implantation failure during implantation window. Reproductive Biology and Endocrinology, 16(1), 1–7. https://doi.org/10.1186/s12958-018-0379-1