{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:49:59Z","timestamp":1787168999404,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hebei Postgraduate Innovation Ability Funding Project","award":["CXZZSS2025087"],"award-info":[{"award-number":["CXZZSS2025087"]}]},{"name":"Hebei Postgraduate Innovation Ability Funding Project","award":["C2024402023"],"award-info":[{"award-number":["C2024402023"]}]},{"name":"Natural Science Foundation of Hebei Province, China","award":["CXZZSS2025087"],"award-info":[{"award-number":["CXZZSS2025087"]}]},{"name":"Natural Science Foundation of Hebei Province, China","award":["C2024402023"],"award-info":[{"award-number":["C2024402023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Estrogen exerts its action via estrogen receptors (ERs), including ER\u03b1 and ER\u03b2, and has effects on immunomodulation during pregnancy. It is known that there are changes in the function of the maternal immune organs during pregnancy. However, it is not clear if early pregnancy has effects on the expression of ER\u03b1 and ER\u03b2 in the ovine maternal thymus, lymph nodes, spleen, and liver. In this study, these maternal immune organs were harvested at day 16 of the estrous cycle and at days 13, 16, and 25 of pregnancy (n = 6 for each group) after the ewes were euthanized. The mRNA and protein expression of ER\u03b1 and ER\u03b2 were analyzed using real-time PCR and Western blot and immunohistochemical analyses. The results reveal that the mRNA and protein expression of both ER\u03b1 and ER\u03b2 were upregulated in the maternal spleen and the expression of ER\u03b1 and ER\u03b2 in the thymus, lymph nodes, and liver was modulated during early pregnancy. In conclusion, early pregnancy modulates the expression of ER\u03b1 and ER\u03b2 in the maternal thymus, lymph nodes, spleen, and liver in a tissue-specific manner, which is related to the regulation of maternal immune function during early pregnancy in ewes.<\/jats:p>","DOI":"10.3390\/ijms26083528","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"3528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expression of Estrogen Receptors in Main Immune Organs in Sheep During Early Pregnancy"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhen","family":"Yang","sequence":"first","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouyuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-8325","authenticated-orcid":false,"given":"Leying","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-0024","authenticated-orcid":false,"given":"Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan 056038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/humupd\/dmad016","article-title":"The pathophysiological role of estrogens in the initial stages of pregnancy: Molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester","volume":"29","author":"Parisi","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1530\/JME-15-0300","article-title":"Mechanisms of uterine estrogen signaling during early pregnancy in mice: An update","volume":"56","author":"Robertshaw","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bai, J., Qi, Q.R., Li, Y., Day, R., Makhoul, J., Magness, R.R., and Chen, D.B. (2020). Estrogen receptors and estrogen-induced uterine vasodilation in pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124349"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yu, K., Huang, Z.Y., Xu, X.L., Li, J., Fu, X.W., and Deng, S.L. (2022). Estrogen receptor function: Impact on the human endometrium. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.827724"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S1995-7645(13)60131-5","article-title":"Effects of estrogen on CD4(+) CD25(+) regulatory T cell in peripheral blood during pregnancy","volume":"6","author":"Xiong","year":"2013","journal-title":"Asian. Pac. J. Trop. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1095\/biolreprod53.6.1527","article-title":"Temporal and spatial alterations in uterine estrogen receptor and progesterone receptor gene expression during the estrous cycle and early pregnancy in the ewe","volume":"53","author":"Spencer","year":"1995","journal-title":"Biol. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Abu-Raya, B., Michalski, C., Sadarangani, M., and Lavoie, P.M. (2020). Maternal immunological adaptation during normal pregnancy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.575197"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gullo, G., Scaglione, M., Cucinella, G., Riva, A., Coldebella, D., Cavaliere, A.F., Signore, F., Buzzaccarini, G., Spagnol, G., and Lagan\u00e0, A.S. (2022). Congenital Zika Syndrome: Genetic avenues for diagnosis and therapy, possible management and long-term outcomes. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051351"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maranto, M., Zaami, S., Restivo, V., Termini, D., Gangemi, A., Tumminello, M., Culmone, S., Billone, V., Cucinella, G., and Gullo, G. (2023). Symptomatic COVID-19 in pregnancy: Hospital cohort data between May 2020 and April 2021, risk factors and medicolegal implications. Diagnostics., 13.","DOI":"10.3390\/diagnostics13061009"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.31083\/j.ceog5007141","article-title":"Androgens and female sexuality: Molecular insights, neuroendocrine crosstalk and future therapeutic directions","volume":"50","author":"Montan","year":"2023","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Quatrini, L., Ricci, B., Ciancaglini, C., Tumino, N., and Moretta, L. (2021). Regulation of the immune system development by glucocorticoids and sex hormones. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.672853"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103973","DOI":"10.1016\/j.jri.2023.103973","article-title":"Autophagy-mediated immune system regulation in reproductive system and pregnancy-associated complications","volume":"158","author":"Komijani","year":"2023","journal-title":"J. Reprod. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/endrev\/bnac017","article-title":"Estrogen receptor signaling in the immune system","volume":"44","author":"Chakraborty","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.theriogenology.2020.04.010","article-title":"Immunological detection of pregnancy: Evidence for systemic immune modulation during early pregnancy in ruminants","volume":"150","author":"Ott","year":"2020","journal-title":"Theriogenology."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e20200048","DOI":"10.1590\/1984-3143-ar2020-0048","article-title":"Conceptus-modulated innate immune function during early pregnancy in ruminants: A review","volume":"18","author":"Rocha","year":"2021","journal-title":"Anim. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106731","DOI":"10.1016\/j.domaniend.2022.106731","article-title":"Early pregnancy regulates the expression of prolactin and its receptor in the thymus, the liver, the spleen and lymph nodes in sheep","volume":"81","author":"Feng","year":"2022","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/imr.13306","article-title":"Primary and secondary defects of the thymus","volume":"322","author":"Dinges","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/eji.201646309","article-title":"Pregnancy-induced thymic involution is associated with suppression of chemokines essential for T-lymphoid progenitor homing","volume":"46","author":"Laan","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Meng, Y., Yang, Z., Quan, Y., Zhao, S., Zhang, L., and Yang, L. (2023). Regulation of IkappaB protein expression by early gestation in the thymus of ewes. Vet. Sci., 10.","DOI":"10.3390\/vetsci10070462"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Taves, M.D., and Ashwell, J.D. (2022). Effects of sex steroids on thymic epithelium and thymocyte development. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.975858"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102468","DOI":"10.1016\/j.autrev.2020.102468","article-title":"Estrogen, estrogen-like molecules and autoimmune diseases","volume":"19","author":"Merrheim","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.12717\/DR.2013.17.4.441","article-title":"Thymocyte differentiation is regulated by a change in estradiol levels during the estrous cycle in mouse","volume":"17","author":"Lee","year":"2013","journal-title":"Dev. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s10517-018-4136-4","article-title":"Hormonal regulation of dendritic cell differentiation in the thymus","volume":"165","author":"Shirshev","year":"2018","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1365-2567.2006.02559.x","article-title":"Murine pregnancy leads to reduced proliferation of maternal thymocytes and decreased thymic emigration","volume":"121","author":"Zoller","year":"2007","journal-title":"Immunology."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"jcs241828","DOI":"10.1242\/jcs.241828","article-title":"The lymph node at a glance\u2014How spatial organization optimizes the immune response","volume":"133","author":"Grant","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"skab208","DOI":"10.1093\/jas\/skab208","article-title":"Characterization of local and peripheral immune system in pregnant and nonpregnant ewes","volume":"99","author":"Quirke","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fang, S., Cai, C., Bai, Y., Zhang, L., and Yang, L. (2023). Early pregnancy regulates expression of IkappaB family in ovine spleen and lymph nodes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065156"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/S0002-9440(10)63490-6","article-title":"Estrogen receptor alpha is a novel marker expressed by follicular dendritic cells in lymph nodes and tumor-associated lymphoid infiltrates","volume":"163","author":"Sapino","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eaau6085","DOI":"10.1126\/sciimmunol.aau6085","article-title":"Structure and function of the immune system in the spleen","volume":"4","author":"Lewis","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cellimm.2007.10.004","article-title":"Estrogen distinctively modulates spleen DC from (NZB x NZW) F1 female mice in various disease development stages","volume":"248","author":"Jiang","year":"2007","journal-title":"Cell Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cellimm.2012.07.007","article-title":"17\u03b2-Estradiol enhances response of mice spleen B cells elicited by TLR9 agonist","volume":"278","author":"Xu","year":"2012","journal-title":"Cell Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, P., Jiang, L.N., Wang, C., Li, Y., Yin, M., Du, H.B., Zhang, H., Fan, Z.H., Liu, Y.X., and Zhao, M. (2021). Estradiol-induced inhibition of endoplasmic reticulum stress normalizes splenic CD4\u2009+\u2009T lymphocytes following hemorrhagic shock. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-87159-1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1642-431X(12)60028-X","article-title":"The influence of mating on estrogen receptor alpha protein level in spleen and uterine macrophages in female mice","volume":"9","author":"Piesta","year":"2009","journal-title":"Reprod. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.22358\/jafs\/146491\/2022","article-title":"Changes in nuclear factor kappa B components expression in the ovine spleen during early pregnancy","volume":"31","author":"Hao","year":"2022","journal-title":"J. Anim. Feed. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yang, L., Meng, Y., Shi, Y., Fang, H., and Zhang, L. (2023). Maternal hepatic immunology during pregnancy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1220323"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/07435800500454528","article-title":"The expression of estrogen, prolactin, and progesterone receptors in mammary gland and liver of female rats during pregnancy and early postpartum: Regulation by thyroid hormones","volume":"31","author":"Varas","year":"2005","journal-title":"Endocr. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1158\/2767-9764.CRC-24-0196","article-title":"Estrogen receptor blockade potentiates immunotherapy for liver metastases by altering the liver immunosuppressive microenvironment","volume":"4","author":"Benslimane","year":"2024","journal-title":"Cancer. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tian, Y., Hong, X., Xie, Y., Guo, Z., and Yu, Q. (2023). 17\u03b2-Estradiol (E2) Upregulates the ER\u03b1\/SIRT1\/PGC-1\u03b1 signaling pathway and protects mitochondrial function to prevent bilateral oophorectomy (OVX)-induced nonalcoholic fatty liver disease (NAFLD). Antioxidants., 12.","DOI":"10.3390\/antiox12122100"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:38Z","timestamp":1760029898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083528"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083528","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]}}}