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Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory polycystic ovarian syndrome (PCOS) patients in the proliferative and secretory phases of the natural menstrual cycle and in 12 infertile anovulatory PCOS patients. Endometrial biopsies and blood samples were evaluated for expression of OPN and CD44 using RT-PCR, immunohistochemistry and ELISA analysis to determine circulating levels of OPN, CD44, TNF-\u03b1, IFN-\u03b3 and OPN and CD44 levels in biopsy media. Our findings highlighted an increased level of circulating OPN and CD44 in serum from infertile patients that inversely correlated with expression levels in endometrial tissue and positively correlated with levels secreted into biopsy media. OPN and CD44 levels positively correlated to each other in serum and media from fertile and PCOS patients, as well as to circulating TNF-\u03b1 and IFN-\u03b3. In vitro analysis revealed that hormone treatment induced recruitment of ER\u03b1 to the OPN and CD44 promoters with a concomitant increase in the expression of these genes. In infertile patients, inflammatory cytokines led to recruitment of NF-\u03baB and STAT1 proteins to the OPN and CD44 promoters, resulting in their overexpression. These observations suggest that the endometrial epithelial OPN-CD44 adhesion complex is deficient in ovulatory PCOS patients and displays an altered stoichiometry in anovulatory patients, which in both cases may perturb apposition. This, together with elevated circulating and local secreted levels of these proteins, may hinder endometrium-trophoblast interactions by saturating OPN and CD44 receptors on the surface of the blastocyst, thereby contributing to the infertility associated with ovulating PCOS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                    <jats:p>\u2022 Endometrial epithelial OPN-CD44 adhesion complex levels are deficient in ovulatory PCOS patients contributing to the endometrial infertility associated with ovulating PCOS patients.<\/jats:p>\n                    <jats:p>\u2022 Circulating levels of OPN, CD44 and inflammatory cytokines TNF-\u03b1 and IFN-\u03b3 are altered in infertile PCOS patients.<\/jats:p>\n                    <jats:p>\u2022 Increased levels of both OPN and CD44 in biopsy media and serum inversely correlate with endometrial expression of these markers in endometrial tissue.<\/jats:p>\n                    <jats:p>\u2022 In infertile PCOS patients, high levels of oestrogens and inflammatory cytokines stimulate the recruitment of transcription factors to the OPN and CD44 promoters to enhance gene transcription.<\/jats:p>\n                    <jats:p>\u2022 Our study identifies a novel crosstalk between the CD44-OPN adhesion complex, ER\u03b1, STAT1 and NF-\u03baB pathways modulating endometrial receptivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-020-01985-w","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T20:02:18Z","timestamp":1602532938000},"page":"1713-1725","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Differential regulation of osteopontin and CD44 correlates with infertility status in PCOS patients"],"prefix":"10.1007","volume":"98","author":[{"given":"R.","family":"Paravati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"De Mello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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