Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establis...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/6/2872 |
| _version_ | 1797541680633610240 |
|---|---|
| author | Ahmad J. H. Albaghdadi Frederick W. K. Kan |
| author_facet | Ahmad J. H. Albaghdadi Frederick W. K. Kan |
| author_sort | Ahmad J. H. Albaghdadi |
| collection | DOAJ |
| description | Polycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establishment of pregnancy in women with PCOS. The accumulating body of evidence obtained from experimental and clinical studies suggests a link between inherent adaptive and innate immune irregularities and aberrant endometrial features in PCOS. The use of conventional therapeutic interventions such as lifestyle modification, metformin and ovarian stimulation has achieved limited clinical success in restoring ovulation and endometrial receptivity in women with PCOS. Unlike other immunosuppressive drugs prescribed in the clinical management of autoimmune and inflammatory disorders that may have deleterious effects on fertility and fetal development, preclinical studies in mice and in women without PCOS but with repeated implantation failure revealed potential therapeutic benefits for the use of low-dose tacrolimus in treating female infertility. Improved systemic and ovarian immune functions, endometrial progesterone receptor and coreceptor expressions and uterine vascular adaptation to pregnancy were among features of enhanced progesterone-receptor sensitivity in the low-dose tacrolimus-treated mouse model of the disease. In this review, we have compiled available experimental and clinical data in literature on endometrial progesterone resistance and current therapeutic options, as well as mechanisms of actions and reported outcomes relevant to the potential therapeutic benefits for the use of low-dose tacrolimus in treating PCOS-associated female infertility. |
| first_indexed | 2024-03-10T13:19:19Z |
| format | Article |
| id | doaj.art-6dff718e55fd40c19d74fa7999f0f362 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:19:19Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6dff718e55fd40c19d74fa7999f0f3622023-11-21T10:10:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226287210.3390/ijms22062872Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary SyndromeAhmad J. H. Albaghdadi0Frederick W. K. Kan1Department of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L 3N6, CanadaDepartment of Biomedical and Molecular Sciences, Faculty of Health Sciences, Queen’s University, Kingston, ON K7L 3N6, CanadaPolycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establishment of pregnancy in women with PCOS. The accumulating body of evidence obtained from experimental and clinical studies suggests a link between inherent adaptive and innate immune irregularities and aberrant endometrial features in PCOS. The use of conventional therapeutic interventions such as lifestyle modification, metformin and ovarian stimulation has achieved limited clinical success in restoring ovulation and endometrial receptivity in women with PCOS. Unlike other immunosuppressive drugs prescribed in the clinical management of autoimmune and inflammatory disorders that may have deleterious effects on fertility and fetal development, preclinical studies in mice and in women without PCOS but with repeated implantation failure revealed potential therapeutic benefits for the use of low-dose tacrolimus in treating female infertility. Improved systemic and ovarian immune functions, endometrial progesterone receptor and coreceptor expressions and uterine vascular adaptation to pregnancy were among features of enhanced progesterone-receptor sensitivity in the low-dose tacrolimus-treated mouse model of the disease. In this review, we have compiled available experimental and clinical data in literature on endometrial progesterone resistance and current therapeutic options, as well as mechanisms of actions and reported outcomes relevant to the potential therapeutic benefits for the use of low-dose tacrolimus in treating PCOS-associated female infertility.https://www.mdpi.com/1422-0067/22/6/2872polycystic ovary syndrome (PCOS)endometrial progesterone resistancetacrolimusimmunosuppressionchronic inflammation |
| spellingShingle | Ahmad J. H. Albaghdadi Frederick W. K. Kan Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome International Journal of Molecular Sciences polycystic ovary syndrome (PCOS) endometrial progesterone resistance tacrolimus immunosuppression chronic inflammation |
| title | Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome |
| title_full | Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome |
| title_fullStr | Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome |
| title_full_unstemmed | Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome |
| title_short | Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome |
| title_sort | therapeutic potentials of low dose tacrolimus for aberrant endometrial features in polycystic ovary syndrome |
| topic | polycystic ovary syndrome (PCOS) endometrial progesterone resistance tacrolimus immunosuppression chronic inflammation |
| url | https://www.mdpi.com/1422-0067/22/6/2872 |
| work_keys_str_mv | AT ahmadjhalbaghdadi therapeuticpotentialsoflowdosetacrolimusforaberrantendometrialfeaturesinpolycysticovarysyndrome AT frederickwkkan therapeuticpotentialsoflowdosetacrolimusforaberrantendometrialfeaturesinpolycysticovarysyndrome |