The effect of intravenous remdesivir on endometrial receptivity in female mice

Jamileh Sadat Mirsanei, Azam Govahi, Zahra Abroodi, Rana Mehdizadeh, Ronak Shabani, Mehdi Mehdiadeh, Mehdi Mehdizadeh, Marziyeh Ajdary
Clinical and experimental reproductive medicine · · doi:10.5653/cerm.2026.09138 · PMID:42710901
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The provided text consists entirely of a reference list and does not contain the abstract or body of the study titled "The effect of intravenous remdesivir on endometrial receptivity in female mice." Consequently, it is impossible to summarize the specific methods, population, or key findings of the primary research described in the title. The references cited include studies on remdesivir toxicity, embryo implantation mechanisms, and cytokine roles in reproduction, but none provide the data from the main paper itself. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

OBJECTIVE: Pregnant women with coronavirus disease 2019 (COVID-19) are more likely than nonpregnant women to require admission to an intensive care unit, and many may require antiviral therapy. Remdesivir, an antiviral drug used to treat COVID-19, may exert toxic effects on specific tissues and organs. Therefore, this study investigated the effects of remdesivir on endometrial tissue in pregnant female mice. METHODS: Thirty female Naval Medical Research Institute (NMRI) mice were divided into five groups. The control group received no treatment, and the sham group received the remdesivir solvent, dimethyl sulfoxide. The 2-, 4-, and 8-mg groups received the corresponding doses of remdesivir. Treatment continued for 10 days. After injection and mating, the presence of a vaginal plug was considered to indicate gestational day 1. On gestational day 4.5, uterine tissue damage, pinopode status, serum estradiol levels, and tissue expression of interleukin-6 and interleukin-1β were examined. RESULTS: Serum estradiol levels and interleukin-6 expression in endometrial tissue decreased in a dose-dependent manner after remdesivir treatment. Remdesivir treatment was also associated with fewer uterine pinopodes and histological evidence of endometrial tissue injury (p<0.05). CONCLUSION: In pregnant mice, remdesivir reduced serum estradiol levels, decreased the number of endometrial pinopodes, and suppressed interleukin-6 expression. These findings suggest that remdesivir may adversely affect the endometrium and potentially compromise implantation; however, direct functional validation is required.
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5. Pagliano P, Sellitto C, Scarpati G, Ascione T, Conti V, Franci G, et al. An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19). Expert Opin Drug Discov 2022;17:9-18. 6. Akinci E, Cha M, Lin L, Yeo G, Hamilton MC, Donahue CJ, et al. Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics. bioRxiv [Preprint] 2020 Aug 28. https://doi.org/10.1101/2020.08.27.270819 8. Govahi A, Nasr-Esfahani MH, Amjadi F, Mahdevar M, Mehdizadeh R, Mehdizadeh M. Cutting-edge techniques provide insights regarding repeated implantation failure patients. Reprod Biomed Online 2023;46:687-96. 9. Hamid HY, Zakaria MZ. Embryo implantation: shedding light on the roles of ovarian hormones, cytokines and growth factors in the implantation process. Afr J Biotechnol 2012;11:16297-304. 12. Atta M, Bakery A, Adel M, Fadl A. Developmental toxicity induced by prenatal exposure to remdesivir in pregnant female rats and their offspring. Egypt Acad J Biol Sci B Zool 2024;16:105-20. 19. Singh M, Chaudhry P, Asselin E. Bridging endometrial receptivity and implantation: network of hormones, cytokines, and growth factors. J Endocrinol 2011;210:5-14. 20. Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, et al. Molecular cues to implantation. Endocr Rev 2004;25:341-73. 21. Lessey BA. Two pathways of progesterone action in the human endometrium: implications for implantation and contraception. Steroids 2003;68:809-15. 23. Basak S, Dhar R, Das C. Steroids modulate the expression of alpha4 integrin in mouse blastocysts and uterus during implantation. Biol Reprod 2002;66:1784-9. 24. Demir R, Yaba A, Huppertz B. Vasculogenesis and angiogenesis in the endometrium during menstrual cycle and implantation. Acta Histochem 2010;112:203-14. 25. Abd ElFattah LI. Pinopodes. Egypt J Histol 2012;35:633-9. 26. Robertson SA, O'Connell A, Ramsey A. The effect of interleukin-6 deficiency on implantation, fetal development and parturition in mice. In: Proceeding of the 31st Annual Conference of the Australian Society for Reproductive Biology; 2000 Apr 26-30; Canberra, Australia. 27. Hinduja I, Pathare AD, Zaveri K, Hinduja I. Immunological approach of personalized treatment for recurrent implantation failure patients undergoing IVF. Glob J Reprod Med 2018;5:65-7. 28. Salama KM, Alloush MK, Al Hussini RM. Are the cytokines TNF alpha and IL 1beta early predictors of embryo implantation?: cross sectional study. J Reprod Immunol 2020;137:102618. 30. Nakamura H, Jasper MJ, Hull ML, Aplin JD, Robertson SA. Macrophages regulate expression of a1,2-fucosyltransferase genes in human endometrial epithelial cells. Mol Hum Reprod 2012;18:204-15. 31. Jasper MJ, Care AS, Sullivan B, Ingman WV, Aplin JD, Robertson SA. Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy. Biol Reprod 2011;84:179-88. 32. Robertson SA, Moldenhauer LM. Immunological determinants of implantation success. Int J Dev Biol 2014;58:205-17. 33. Cohen M, Meisser A, Haenggeli L, Bischof P. Involvement of MAPK pathway in TNF-alpha-induced MMP-9 expression in human trophoblastic cells. Mol Hum Reprod 2006;12:225-32. 35. Meisser A, Chardonnens D, Campana A, Bischof P. Effects of tumour necrosis factor-alpha, interleukin-1 alpha, macrophage colony stimulating factor and transforming growth factor beta on trophoblastic matrix metalloproteinases. Mol Hum Reprod 1999;5:252-60.

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