胚胎著床是生殖過程中的關鍵步驟，需要胎盤和母體微環境之間同步的分子對話。新興證據突顯了由多樣化細菌群落組成的陰道微生物組在塑造子宮內膜微環境和影響生殖結果中的重要作用。我們先前的研究發現，病原體 Atopobium vaginae 在非懷孕個體的豐度明顯較高。A. vaginae是一種與細菌性陰道炎（BV）相關的革蘭氏陽性厭氧菌，則是已知和懷孕失敗和不孕症相關。然而，A. vaginae在陰道微環境中的具體作用及其對胚胎著床的影響仍不清楚。本研究中假設陰道微生物組通過分泌代謝物來影響子宮內膜微環境，可能導致著床失敗。因此，本研究旨在研究陰道微生物組代謝物在改變子宮內膜微環境和導致胚胎著床失敗中的鑑定和表徵。A. vaginae 在厭氧條件下於補充的 Brucella broth 中培養 5 天。收集細菌培養物的上清液並過濾，然後進行 LC-MS/MS 分析。使用ProteoWizard軟體和KEGG數據庫分析所得數據，以鑑定和定量代謝物特徵。通過使用培養A. vaginae之條件培養基培養VK2/E6E7細胞，研究A. vaginae代謝物對陰道上皮細胞增殖的影響。LC-MS/MS分析顯示，與對照樣本相比，A. vaginae培養物具有獨特的代謝物譜，共鑑定出8,273種顯著代謝化合物。這些鑑定的代謝物主要分為四大類：carboxylic acids and derivatives, benzene and substituted derivatives, indoles and derivatives, and steroids and以及steroid derivatives。使用 KEGG 資料庫進行的富集分析確定精氨酸和脯氨酸生物合成是與發炎相關的最重要的代謝途徑.當使用 AV 條件培養基培養時，VK2/E6E7 陰道上皮細胞系顯示細胞增殖減少，表明潛在的代謝物誘導的局部發炎。代謝組學分析揭示了不同的表達模式，暴露於 AV 條件培養基的 VK2/E6E7 細胞中，幾種關鍵代謝物的水平升高，包括 indole, 5-hydroxyindoleacetic acid, 以及3-indole acetonitrile。此外，riboflavin metabolism成為經處理的 VK2/E6E7 細胞中最顯著改變的代謝途徑，顯示其在引發發炎反應中的作用。我們的研究對 AV 和陰道上皮細胞之間的代謝相互作用進行了開創性的探索，強調了解特定細菌代謝功能在生殖健康中的至關重要性。

Embryo implantation is a critical step in the reproductive process, requiring synchronized molecular dialogue between the trophoblast and the maternal microenvironment. Emerging evidence highlights the significant role of the vaginal microbiome, composed of diverse bacterial communities, in shaping the endometrial microenvironment and influencing reproductive outcomes. Our previous study found that the pathogen Atopobium vaginae species had a significantly higher abundance in non-pregnant individuals. A. vaginae, a gram-positive anaerobic bacterium connected to bacterial vaginosis (BV), has been associated with unsuccessful pregnancies and infertility. However, the specific role of A. vaginae in the vaginal microenvironment and its impact on embryo implantation remains unclear. We hypothesize that the vaginal microbiome influences the endometrial microenvironment through the secretion of metabolites, potentially leading to implantation failure. Thus, the current project aims to study the identification and characterization of metabolites of the vaginal microbiome in altering the endometrium microenvironment and resulting in embryo implantation failure. A. vaginae was cultured in supplemented Brucella broth for 5 days under anaerobic conditions. The supernatant from the bacterial culture was collected and filtered, then subjected to LC-MS/MS analysis. We used ProteoWizard software for data analysis and KEGG databases to identify and quantify the metabolite features. The impact of metabolites from A. vaginae on the proliferation of vaginal epithelial cells was examined by culturing the VK2/E6E7 cell line with A. vaginae-conditioned medium. The LC-MS/MS analysis revealed a distinct metabolite profile of A. vaginae culture compared to the control sample, with 8,273 significant metabolite compounds identified. Most of these identified metabolites were classified into four main categories: carboxylic acids and derivatives, benzene and substituted derivatives, indoles and derivatives, steroids and steroid derivatives. An enrichment analysis using the KEGG database identified arginine and proline biosynthesis as the most prominent metabolic pathways associated with inflammation. When cultured with A. vaginae-conditioned medium, the VK2/E6E7 vaginal epithelial cell line showed reduced cell proliferation, indicating potential metabolite-induced local inflammation. Metabolomic profiling revealed distinct expression patterns, with several key metabolites showing elevated levels in VK2/E6E7 cells exposed to A. vaginae-conditioned medium, including indole, 5-hydroxyindoleacetic acid, and 3-indole acetonitrile. Additionally, riboflavin metabolism emerged as the most significantly altered metabolic pathway in treated VK2/E6E7 cells, suggesting its role in initiating inflammatory responses. Our study presents a pioneering exploration of the metabolic interactions between A. vaginae and vaginal epithelial cells, highlighting the critical importance of understanding specific bacterial metabolite functions in reproductive health.

Adapen, C., Reot, L., & Menu, E. (2022). Role of the human vaginal microbiota in the regulation of inflammation and sexually transmitted infection acquisition: Contribution of the non-human primate model to a better understanding? Front Reprod Health, 4, 992176. https://doi.org/10.3389/frph.2022.992176
Aghajanova, L. (2004). Leukemia inhibitory factor and human embryo implantation. Ann N Y Acad Sci, 1034, 176-183. https://doi.org/10.1196/annals.1335.020
Ahn, H., & Lee, G. S. (2020). Riboflavin, vitamin B2, attenuates NLRP3, NLRC4, AIM2, and non-canonical inflammasomes by the inhibition of caspase-1 activity. Sci Rep, 10(1), 19091. https://doi.org/10.1038/s41598-020-76251-7
Al-Najjar, M. A. A., Abdulrazzaq, S. B., Alzaghari, L. F., Mahmod, A. I., Omar, A., Hasen, E., Athamneh, T., Talib, W. H., Chellappan, D. K., & Barakat, M. (2024). Evaluation of immunomodulatory potential of probiotic conditioned medium on murine macrophages. Sci Rep, 14(1), 7126. https://doi.org/10.1038/s41598-024-56622-0
Al-Nasiry, S., Ambrosino, E., Schlaepfer, M., Morre, S. A., Wieten, L., Voncken, J. W., Spinelli, M., Mueller, M., & Kramer, B. W. (2020). The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction. Front Immunol, 11, 378. https://doi.org/10.3389/fimmu.2020.00378
Aldunate, M., Srbinovski, D., Hearps, A. C., Latham, C. F., Ramsland, P. A., Gugasyan, R., Cone, R. A., & Tachedjian, G. (2015). Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front Physiol, 6, 164. https://doi.org/10.3389/fphys.2015.00164
Alexeev, E. E., Lanis, J. M., Kao, D. J., Campbell, E. L., Kelly, C. J., Battista, K. D., Gerich, M. E., Jenkins, B. R., Walk, S. T., Kominsky, D. J., & Colgan, S. P. (2018). Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor. Am J Pathol, 188(5), 1183-1194. https://doi.org/10.1016/j.ajpath.2018.01.011
Aljanabi, S. M., & Martinez, I. (1997). Universal and rapid salt-extraction of high quality genomic DNA for PCR-based techniques. Nucleic Acids Res, 25(22), 4692-4693. https://doi.org/10.1093/nar/25.22.4692
Alsharhan, H., & Ficicioglu, C. (2020). Disorders of phenylalanine and tyrosine metabolism. Translational Science of Rare Diseases, 5(1-2), 3-58. https://doi.org/10.3233/trd-200049
Anton, L., Ferguson, B., Friedman, E. S., Gerson, K. D., Brown, A. G., & Elovitz, M. A. (2022). Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses. Microbiome, 10(1), 119. https://doi.org/10.1186/s40168-022-01317-9
Auguet, T., Bertran, L., Capellades, J., Abello, S., Aguilar, C., Sabench, F., Del Castillo, D., Correig, X., Yanes, O., & Richart, C. (2023). LC/MS-Based Untargeted Metabolomics Analysis in Women with Morbid Obesity and Associated Type 2 Diabetes Mellitus. Int J Mol Sci, 24(9). https://doi.org/10.3390/ijms24097761
Aunapuu, M., Kibur, P., Jarveots, T., & Arend, A. (2018). Changes in Morphology and Presence of Pinopodes in Endometrial Cells during the Luteal Phase in Women with Infertility Problems: A Pilot Study. Medicina (Kaunas), 54(5). https://doi.org/10.3390/medicina54050069
Avitabile, E., Menotti, L., Croatti, V., Giordani, B., Parolin, C., & Vitali, B. (2024). Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections. Int J Mol Sci, 25(17). https://doi.org/10.3390/ijms25179168
Barbier, T., Zuniga-Ripa, A., Moussa, S., Plovier, H., Sternon, J. F., Lazaro-Anton, L., Conde-Alvarez, R., De Bolle, X., Iriarte, M., Moriyon, I., & Letesson, J. J. (2018). Brucella central carbon metabolism: an update. Crit Rev Microbiol, 44(2), 182-211. https://doi.org/10.1080/1040841X.2017.1332002
Bergstrand, L. H., Cardenas, E., Holert, J., Van Hamme, J. D., & Mohn, W. W. (2016). Delineation of Steroid-Degrading Microorganisms through Comparative Genomic Analysis. mBio, 7(2), e00166. https://doi.org/10.1128/mBio.00166-16
Bi, S., Kargeti, M., Colin, R., Farke, N., Link, H., & Sourjik, V. (2023). Dynamic fluctuations in a bacterial metabolic network. Nat Commun, 14(1), 2173. https://doi.org/10.1038/s41467-023-37957-0
Biggers, J. D. (2012). IVF and embryo transfer: historical origin and development. Reprod Biomed Online, 25(2), 118-127. https://doi.org/10.1016/j.rbmo.2012.04.011
Bischof, P., & Campana, A. (2000). Molecular mediators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol, 14(5), 801-814. https://doi.org/10.1053/beog.2000.0120
Borgogna, J. C., Shardell, M. D., Grace, S. G., Santori, E. K., Americus, B., Li, Z., Ulanov, A., Forney, L., Nelson, T. M., Brotman, R. M., Ravel, J., & Yeoman, C. J. (2021). Biogenic Amines Increase the Odds of Bacterial Vaginosis and Affect the Growth of and Lactic Acid Production by Vaginal Lactobacillus spp. Appl Environ Microbiol, 87(10). https://doi.org/10.1128/AEM.03068-20
Bozzini, G., Provenzano, M., Buffi, N., Seveso, M., Lughezzani, G., Guazzoni, G., Mandressi, A., & Taverna, G. (2016). An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men. BMC Urol, 16(1), 25. https://doi.org/10.1186/s12894-016-0144-8
Bradford, L. L., & Ravel, J. (2017). The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases. Virulence, 8(3), 342-351. https://doi.org/10.1080/21505594.2016.1237332
Brauer, M. M., & Smith, P. G. (2015). Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity. Auton Neurosci, 187, 1-17. https://doi.org/10.1016/j.autneu.2014.11.009
Brennan, C., Chan, K., Kumar, T., Maissy, E., Brubaker, L., Dothard, M. I., Gilbert, J. A., Gilbert, K. E., Lewis, A. L., Thackray, V. G., Zarrinpar, A., & Knight, R. (2024). Harnessing the power within: engineering the microbiome for enhanced gynecologic health. Reprod Fertil, 5(2). https://doi.org/10.1530/RAF-23-0060
Brown, D., & Turner, R. J. (2021). Assessing microbial growth monitoring methods for challenging strains and cultures. bioRxiv. https://doi.org/10.1101/2021.10.05.463247
Burton, G. J., Jauniaux, E., & Murray, A. J. (2017). Oxygen and placental development; parallels and differences with tumour biology. Placenta, 56, 14-18. https://doi.org/https://doi.org/10.1016/j.placenta.2017.01.130
Campisciano, G., Florian, F., D'Eustacchio, A., Stankovic, D., Ricci, G., De Seta, F., & Comar, M. (2017). Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility. J Cell Physiol, 232(7), 1681-1688. https://doi.org/10.1002/jcp.25806
Carlson, H. K., Lui, L. M., Price, M. N., Kazakov, A. E., Carr, A. V., Kuehl, J. V., Owens, T. K., Nielsen, T., Arkin, A. P., & Deutschbauer, A. M. (2020). Selective carbon sources influence the end products of microbial nitrate respiration. ISME J, 14(8), 2034-2045. https://doi.org/10.1038/s41396-020-0666-7
Caselli, E., Soffritti, I., D'Accolti, M., Piva, I., Greco, P., & Bonaccorsi, G. (2019). Atopobium vaginae And Porphyromonas somerae Induce Proinflammatory Cytokines Expression In Endometrial Cells: A Possible Implication For Endometrial Cancer? Cancer Manag Res, 11, 8571-8575. https://doi.org/10.2147/CMAR.S217362
Castro-Sobrinho, J. M. D., Rabelo-Santos, S. H., Fugueiredo-Alves, R. R., Derchain, S., Sarian, L. O., Pitta, D. R., Campos, E. A., & Zeferino, L. C. (2017). Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women. Diagn Cytopathol, 45(5), 474-476. https://doi.org/10.1002/dc.23641
Cha, J., Sun, X., & Dey, S. K. (2012). Mechanisms of implantation: strategies for successful pregnancy. Nat Med, 18(12), 1754-1767. https://doi.org/10.1038/nm.3012
Chang, J. D., Vaughan, E. E., Liu, C. G., Jelinski, J. W., Terwilliger, A. L., & Maresso, A. W. (2021). Metabolic profiling reveals nutrient preferences during carbon utilization in Bacillus species. Sci Rep, 11(1), 23917. https://doi.org/10.1038/s41598-021-03420-7
Chen, C., Song, X., Wei, W., Zhong, H., Dai, J., Lan, Z., Li, F., Yu, X., Feng, Q., Wang, Z., Xie, H., Chen, X., Zeng, C., Wen, B., Zeng, L., Du, H., Tang, H., Xu, C., Xia, Y., Xia, H., Yang, H., Wang, J., Wang, J., Madsen, L., Brix, S., Kristiansen, K., Xu, X., Li, J., Wu, R., & Jia, H. (2017). The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun, 8(1), 875. https://doi.org/10.1038/s41467-017-00901-0
Chen, M. X., Wang, S. Y., Kuo, C. H., & Tsai, I. L. (2019). Metabolome analysis for investigating host-gut microbiota interactions. J Formos Med Assoc, 118 Suppl 1, S10-S22. https://doi.org/10.1016/j.jfma.2018.09.007
Chen, P., Chen, P., Guo, Y., Fang, C., & Li, T. (2021). Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure. Front Immunol, 12, 748447. https://doi.org/10.3389/fimmu.2021.748447
Cicinelli, E., De Ziegler, D., Nicoletti, R., Colafiglio, G., Saliani, N., Resta, L., Rizzi, D., & De Vito, D. (2008). Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril, 89(3), 677-684. https://doi.org/10.1016/j.fertnstert.2007.03.074
Clayton, G. L., Borges, M. C., & Lawlor, D. A. (2024). The impact of reproductive factors on the metabolic profile of females from menarche to menopause. Nat Commun, 15(1), 1103. https://doi.org/10.1038/s41467-023-44459-6
Cools, P., Verstraelen, H., Vaneechoutte, M., & Verhelst, P. (2011). Molecular Detection of Human Bacterial Pathogens. CRC Press. https://doi.org/http://dx.doi.org/10.1201/b10848-6
Corfield, A. P., Myerscough, N., Longman, R., Sylvester, P., Arul, S., & Pignatelli, M. (2000). Mucins and mucosal protection in the gastrointestinal tract: new prospects for mucins in the pathology of gastrointestinal disease. Gut, 47(4), 589-594. https://doi.org/10.1136/gut.47.4.589
Dahal, U. P., Jones, J. P., Davis, J. A., & Rock, D. A. (2011). Small molecule quantification by liquid chromatography-mass spectrometry for metabolites of drugs and drug candidates. Drug Metab Dispos, 39(12), 2355-2360. https://doi.org/10.1124/dmd.111.040865
Dala-Paula, B. M., Custódio, F., & Gloria, M. B. A. (2023). Health concerns associated with biogenic amines in food and interaction with amine oxidase drugs. Current Opinion in Food Science, 54. https://doi.org/ARTN10109010.1016/j.cofs.2023.101090
Delgado-Diaz, D. J., Tyssen, D., Hayward, J. A., Gugasyan, R., Hearps, A. C., & Tachedjian, G. (2019). Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota. Front Cell Infect Microbiol, 9, 446. https://doi.org/10.3389/fcimb.2019.00446
DeLong, K., Zulfiqar, F., Hoffmann, D. E., Tarzian, A. J., & Ensign, L. M. (2019). Vaginal Microbiota Transplantation: The Next Frontier. J Law Med Ethics, 47(4), 555-567. https://doi.org/10.1177/1073110519897731
Di Pietro, C., Cicinelli, E., Guglielmino, M. R., Ragusa, M., Farina, M., Palumbo, M. A., & Cianci, A. (2013). Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. Am J Reprod Immunol, 69(5), 509-517. https://doi.org/10.1111/aji.12076
Didriksen, B. J., Eshleman, E. M., & Alenghat, T. (2024). Epithelial regulation of microbiota-immune cell dynamics. Mucosal Immunol, 17(2), 303-313. https://doi.org/10.1016/j.mucimm.2024.02.008
Donova, M. (2021). Microbial Steroid Production Technologies: Current Trends and Prospects. Microorganisms, 10(1). https://doi.org/10.3390/microorganisms10010053
Dowling, P., & Clynes, M. (2011). Conditioned media from cell lines: a complementary model to clinical specimens for the discovery of disease-specific biomarkers. Proteomics, 11(4), 794-804. https://doi.org/10.1002/pmic.201000530
Dricot, C., Erreygers, I., Cauwenberghs, E., De Paz, J., Spacova, I., Verhoeven, V., Ahannach, S., & Lebeer, S. (2024). Riboflavin for women's health and emerging microbiome strategies. NPJ Biofilms Microbiomes, 10(1), 107. https://doi.org/10.1038/s41522-024-00579-5
Dukovski, I., Bajic, D., Chacon, J. M., Quintin, M., Vila, J. C. C., Sulheim, S., Pacheco, A. R., Bernstein, D. B., Riehl, W. J., Korolev, K. S., Sanchez, A., Harcombe, W. R., & Segre, D. (2021). A metabolic modeling platform for the computation of microbial ecosystems in time and space (COMETS). Nat Protoc, 16(11), 5030-5082. https://doi.org/10.1038/s41596-021-00593-3
Dunn, C. L., Kelly, R. W., & Critchley, H. O. (2003). Decidualization of the human endometrial stromal cell: an enigmatic transformation. Reprod Biomed Online, 7(2), 151-161. https://doi.org/10.1016/s1472-6483(10)61745-2
Edwards, V. L., McComb, E., Gleghorn, J. P., Forney, L., Bavoil, P. M., & Ravel, J. (2022). Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections. Pathog Dis, 80(1). https://doi.org/10.1093/femspd/ftac026
Elnashar, A. M. (2021). Impact of endometrial microbiome on fertility. Middle East Fertility Society Journal, 26(1). https://doi.org/10.1186/s43043-020-00050-3
Elwood, C., Albert, A., McClymont, E., Wagner, E., Mahal, D., Devakandan, K., Quiqley, B. L., Pakzad, Z., Yudin, M. H., Hill, J. E., Money, D., & Group, V. R. (2020). Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study. BJOG, 127(2), 250-259. https://doi.org/10.1111/1471-0528.15930
Espinos, J. J., Fabregues, F., Fontes, J., Garcia-Velasco, J. A., Llacer, J., Requena, A., Checa, M. A., Bellver, J., & Spanish Infertility, S. G. (2021). Impact of chronic endometritis in infertility: a SWOT analysis. Reprod Biomed Online, 42(5), 939-951. https://doi.org/10.1016/j.rbmo.2021.02.003
Felger, J. C., Li, L., Marvar, P. J., Woolwine, B. J., Harrison, D. G., Raison, C. L., & Miller, A. H. (2013). Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations. Brain Behav Immun, 31, 153-160. https://doi.org/10.1016/j.bbi.2012.10.010
Finamore, P. S., Hunter, K., Goldstein, H. B., Vakili, B., & Holzberg, A. S. (2011). Does local injection with lidocaine plus epinephrine prior to vaginal reconstructive surgery with synthetic mesh affect exposure rates? A retrospective comparison. Arch Gynecol Obstet, 284(3), 659-662. https://doi.org/10.1007/s00404-010-1715-7
Foulk, R. A. (2012). Advances in Embryo Transfer (Vol. Chapter 14). InTech. https://www.intechopen.com/
Franasiak, J. M. (2019). Chronic endometritis is associated with an altered microbiome, but what about treatment and clinical outcomes? Fertil Steril, 112(4), 649-650. https://doi.org/10.1016/j.fertnstert.2019.06.019
Fritz, R., Jain, C., & Armant, D. R. (2014). Cell signaling in trophoblast-uterine communication. Int J Dev Biol, 58(2-4), 261-271. https://doi.org/10.1387/ijdb.140011da
Gajer, P., Brotman, R. M., Bai, G., Sakamoto, J., Schutte, U. M., Zhong, X., Koenig, S. S., Fu, L., Ma, Z. S., Zhou, X., Abdo, Z., Forney, L. J., & Ravel, J. (2012). Temporal dynamics of the human vaginal microbiota. Sci Transl Med, 4(132), 132ra152. https://doi.org/10.1126/scitranslmed.3003605
Gajer, P., Brotman, R. M., Bai, G., Sakamoto, J., Schütte, U. M. E., Zhong, X., Koenig, S. S. K., Fu, L., Ma, Z., Zhou, X., Abdo, Z., Forney, L. J., & Ravel, J. (2012). Temporal Dynamics of the Human Vaginal Microbiota. Sci Transl Med, 4(132).
Galbraith, S. C., Bhatia, H., Liu, H. L., & Yoon, S. (2018). Media formulation optimization: current and future opportunities. Current Opinion in Chemical Engineering, 22, 42-47. https://doi.org/10.1016/j.coche.2018.08.004
Garcia-Gomez, E., Gonzalez-Pedrajo, B., & Camacho-Arroyo, I. (2013). Role of sex steroid hormones in bacterial-host interactions. Biomed Res Int, 2013, 928290. https://doi.org/10.1155/2013/928290
Garcia-Grau, I., Perez-Villaroya, D., Bau, D., Gonzalez-Monfort, M., Vilella, F., Moreno, I., & Simon, C. (2019). Taxonomical and Functional Assessment of the Endometrial Microbiota in A Context of Recurrent Reproductive Failure: A Case Report. Pathogens, 8(4). https://doi.org/10.3390/pathogens8040205
Gokulan, K., Khare, S., & Cerniglia, C. (2014). Metabolic Pathways | Production of Secondary Metabolites of Bacteria. In Encyclopedia of Food Microbiology (pp. 561-569). https://doi.org/10.1016/b978-0-12-384730-0.00203-2
Haahr, T., Humaidan, P., Elbaek, H. O., Alsbjerg, B., Laursen, R. J., Rygaard, K., Johannesen, T. B., Andersen, P. S., Ng, K. L., & Jensen, J. S. (2019). Vaginal Microbiota and In Vitro Fertilization Outcomes: Development of a Simple Diagnostic Tool to Predict Patients at Risk of a Poor Reproductive Outcome. J Infect Dis, 219(11), 1809-1817. https://doi.org/10.1093/infdis/jiy744
Haahr, T., Jensen, J. S., Thomsen, L., Duus, L., Rygaard, K., & Humaidan, P. (2016). Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod, 31(4), 795-803. https://doi.org/10.1093/humrep/dew026
Halasz, M., & Szekeres-Bartho, J. (2013). The role of progesterone in implantation and trophoblast invasion. J Reprod Immunol, 97(1), 43-50. https://doi.org/10.1016/j.jri.2012.10.011
Han, J. T., Li, D. Y., Zhang, M. Y., Yu, X. Q., Jia, X. X., Xu, H., Yan, X., Jia, W. J., Niu, S., Kempher, M. L., Tao, X., & He, Y. X. (2021). EmhR is an indole-sensing transcriptional regulator responsible for the indole-induced antibiotic tolerance in Pseudomonas fluorescens. Environ Microbiol, 23(4), 2054-2069. https://doi.org/10.1111/1462-2920.15354
Han, Y., Liu, Z., & Chen, T. (2021). Role of Vaginal Microbiota Dysbiosis in Gynecological Diseases and the Potential Interventions. Front Microbiol, 12, 643422. https://doi.org/10.3389/fmicb.2021.643422
Hasanin, A. M., Abou Amer, A., Hassabelnaby, Y. S., Mostafa, M., Abdelnasser, A., Amin, S. M., Elsherbiny, M., & Refaat, S. (2023). The use of epinephrine infusion for the prevention of spinal hypotension during Caesarean delivery: A randomized controlled dose-finding trial. Anaesth Crit Care Pain Med, 42(3), 101204. https://doi.org/10.1016/j.accpm.2023.101204
Hashimoto, T., & Kyono, K. (2019). Does dysbiotic endometrium affect blastocyst implantation in IVF patients? J Assist Reprod Genet, 36(12), 2471-2479. https://doi.org/10.1007/s10815-019-01630-7
He, F., Wu, X., Zhang, Q., Li, Y., Ye, Y., Li, P., Chen, S., Peng, Y., Hardeland, R., & Xia, Y. (2021). Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights. Front Immunol, 12, 683879. https://doi.org/10.3389/fimmu.2021.683879
Hill, D. R., Brunner, M. E., Schmitz, D. C., Davis, C. C., Flood, J. A., Schlievert, P. M., Wang-Weigand, S. Z., & Osborn, T. W. (2005). In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses. J Appl Physiol (1985), 99(4), 1582-1591. https://doi.org/10.1152/japplphysiol.01422.2004
Hill, J. A. (2001). Maternal-embryonic cross-talk. Ann N Y Acad Sci, 943, 17-25. https://doi.org/10.1111/j.1749-6632.2001.tb03786.x
Hirakawa, H., Hayashi-Nishino, M., Yamaguchi, A., & Nishino, K. (2010). Indole enhances acid resistance in Escherichia coli. Microb Pathog, 49(3), 90-94. https://doi.org/10.1016/j.micpath.2010.05.002
Hong, I. S. (2023). Endometrial stem/progenitor cells: Properties, origins, and functions. Genes Dis, 10(3), 931-947. https://doi.org/10.1016/j.gendis.2022.08.009
Hoshino, Y., & Gaucher, E. A. (2021). Evolution of bacterial steroid biosynthesis and its impact on eukaryogenesis. PNAS, 118(25). https://doi.org/10.1073/pnas.2101276118
Howard, M. F., Bina, X. R., & Bina, J. E. (2019). Indole Inhibits ToxR Regulon Expression in Vibrio cholerae. Infect Immun, 87(3). https://doi.org/10.1128/IAI.00776-18
Hu, M., Zhang, C., Mu, Y., Shen, Q., & Feng, Y. (2010). Indole affects biofilm formation in bacteria. Indian J Microbiol, 50(4), 362-368. https://doi.org/10.1007/s12088-011-0142-1
Huang, H. Y., Wen, Y., Irwin, J. C., Kruessel, J. S., Soong, Y. K., & Polan, M. L. (1998). Cytokine-mediated regulation of 92-kilodalton type IV collagenase, tissue inhibitor or metalloproteinase-1 (TIMP-1), and TIMP-3 messenger ribonucleic acid expression in human endometrial stromal cells. J Clin Endocrinol Metab, 83(5), 1721-1729. https://doi.org/10.1210/jcem.83.5.4810
Hubbard, T. D., Murray, I. A., Bisson, W. H., Lahoti, T. S., Gowda, K., Amin, S. G., Patterson, A. D., & Perdew, G. H. (2015). Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep, 5, 12689. https://doi.org/10.1038/srep12689
Hyland, N. P., Cavanaugh, C. R., & Hornby, P. J. (2022). Emerging effects of tryptophan pathway metabolites and intestinal microbiota on metabolism and intestinal function. Amino Acids, 54(1), 57-70. https://doi.org/10.1007/s00726-022-03123-x
Hyman, R. W., Herndon, C. N., Jiang, H., Palm, C., Fukushima, M., Bernstein, D., Vo, K. C., Zelenko, Z., Davis, R. W., & Giudice, L. C. (2012). The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer. J Assist Reprod Genet, 29(2), 105-115. https://doi.org/10.1007/s10815-011-9694-6
Ilhan, Z. E., Laniewski, P., Tonachio, A., & Herbst-Kralovetz, M. M. (2020). Members of Prevotella Genus Distinctively Modulate Innate Immune and Barrier Functions in a Human Three-Dimensional Endometrial Epithelial Cell Model. J Infect Dis, 222(12), 2082-2092. https://doi.org/10.1093/infdis/jiaa324
Jandu, N., Ceponis, P. J., Kato, S., Riff, J. D., McKay, D. M., & Sherman, P. M. (2006). Conditioned medium from enterohemorrhagic Escherichia coli-infected T84 cells inhibits signal transducer and activator of transcription 1 activation by gamma interferon. Infect Immun, 74(3), 1809-1818. https://doi.org/10.1128/IAI.74.3.1809-1818.2006
Janiga-MacNelly, A., Vrazel, M., Roat, A. E., Fernandez-Luna, M. T., & Lavado, R. (2025). Exploring the biological impact of bacteria-derived indole compounds on human cell health: Cytotoxicity and cell proliferation across six cell lines. Toxicology Reports, 14. https://doi.org/10.1016/j.toxrep.2024.101883
Jarboe, L. R., Royce, L. A., & Liu, P. (2013). Understanding biocatalyst inhibition by carboxylic acids. Front Microbiol, 4, 272. https://doi.org/10.3389/fmicb.2013.00272
Johnston-MacAnanny, E. B., Hartnett, J., Engmann, L. L., Nulsen, J. C., Sanders, M. M., & Benadiva, C. A. (2010). Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril, 93(2), 437-441. https://doi.org/10.1016/j.fertnstert.2008.12.131
Joseph, R. J., Ser, H. L., Kuai, Y. H., Tan, L. T., Arasoo, V. J. T., Letchumanan, V., Wang, L., Pusparajah, P., Goh, B. H., Ab Mutalib, N. S., Chan, K. G., & Lee, L. H. (2021). Finding a Balance in the Vaginal Microbiome: How Do We Treat and Prevent the Occurrence of Bacterial Vaginosis? Antibiotics (Basel), 10(6). https://doi.org/10.3390/antibiotics10060719
Kamiyama, S., Teruya, Y., Nohara, M., & Kanazawa, K. (2004). Bacterial endotoxin in the endometrium and its clinical significance in reproduction. Fertil Steril, 82(4), 805. https://doi.org/10.1016/j.fertnstert.2004.06.030
Kasius, J. C., Fatemi, H. M., Bourgain, C., Sie-Go, D. M., Eijkemans, R. J., Fauser, B. C., Devroey, P., & Broekmans, F. J. (2011). The impact of chronic endometritis on reproductive outcome. Fertil Steril, 96(6), 1451-1456. https://doi.org/10.1016/j.fertnstert.2011.09.039
Kelleher, A. M., Peng, W., Pru, J. K., Pru, C. A., DeMayo, F. J., & Spencer, T. E. (2017). Forkhead box a2 (FOXA2) is essential for uterine function and fertility. PNAS, 114(6), E1018-E1026. https://doi.org/10.1073/pnas.1618433114
Kim, S. K., Park, H. Y., & Lee, J. H. (2015). Anthranilate deteriorates the structure of Pseudomonas aeruginosa biofilms and antagonizes the biofilm-enhancing indole effect. Appl Environ Microbiol, 81(7), 2328-2338. https://doi.org/10.1128/AEM.03551-14
Kim, S. M., & Kim, J. S. (2017). A Review of Mechanisms of Implantation. Dev Reprod, 21(4), 351-359. https://doi.org/10.12717/DR.2017.21.4.351
Kindinger, L. M., Bennett, P. R., Lee, Y. S., Marchesi, J. R., Smith, A., Cacciatore, S., Holmes, E., Nicholson, J. K., Teoh, T. G., & MacIntyre, D. A. (2017). The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome, 5(1), 6. https://doi.org/10.1186/s40168-016-0223-9
Knight, R., Vrbanac, A., Taylor, B. C., Aksenov, A., Callewaert, C., Debelius, J., Gonzalez, A., Kosciolek, T., McCall, L. I., McDonald, D., Melnik, A. V., Morton, J. T., Navas, J., Quinn, R. A., Sanders, J. G., Swafford, A. D., Thompson, L. R., Tripathi, A., Xu, Z. Z., Zaneveld, J. R., Zhu, Q., Caporaso, J. G., & Dorrestein, P. C. (2018). Best practices for analysing microbiomes. Nat Rev Microbiol, 16(7), 410-422. https://doi.org/10.1038/s41579-018-0029-9
Knofler, M., Haider, S., Saleh, L., Pollheimer, J., Gamage, T., & James, J. (2019). Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci, 76(18), 3479-3496. https://doi.org/10.1007/s00018-019-03104-6
Kong, Y., Liu, Z., Shang, Q., Gao, Y., Li, X., Zheng, C., Deng, X., & Chen, T. (2020). The Disordered Vaginal Microbiota Is a Potential Indicator for a Higher Failure of in vitro Fertilization. Front Med (Lausanne), 7, 217. https://doi.org/10.3389/fmed.2020.00217
Korpela, S. P., Hinz, T. K., Oweida, A., Kim, J., Calhoun, J., Ferris, R., Nemenoff, R. A., Karam, S. D., Clambey, E. T., & Heasley, L. E. (2021). Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response. J Transl Med, 19(1), 43. https://doi.org/10.1186/s12967-021-02706-8
Krussel, J. S., Bielfeld, P., Polan, M. L., & Simon, C. (2003). Regulation of embryonic implantation. Eur J Obstet Gynecol Reprod Biol, 110 Suppl 1, S2-9. https://doi.org/10.1016/s0301-2115(03)00167-2
Kumakura, D., Yamaguchi, R., Hara, A., & Nakaoka, S. (2023). Disentangling the growth curve of microbial culture. J Theor Biol, 573, 111597. https://doi.org/10.1016/j.jtbi.2023.111597
Kumar, P., Ahma, M. I., Singh, S., Pratam, M., Rizki, F., & Mishra, A. K. (2022). Recent advancements on biological activity of indole and their derivatives: A review. The Thai Journal of Pharmaceutical Sciences, 46(3), 233-250. https://doi.org/10.56808/3027-7922.2567
Kumar, P., Lee, J. H., & Lee, J. (2021). Diverse roles of microbial indole compounds in eukaryotic systems. Biol Rev Camb Philos Soc, 96(6), 2522-2545. https://doi.org/10.1111/brv.12765
Kyono, K., Hashimoto, T., Kikuchi, S., Nagai, Y., & Sakuraba, Y. (2019). A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reprod Med Biol, 18(1), 72-82. https://doi.org/10.1002/rmb2.12250
Kyono, K., Hashimoto, T., Nagai, Y., & Sakuraba, Y. (2018). Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol, 17(3), 297-306. https://doi.org/10.1002/rmb2.12105
Lai, Z., Tsugawa, H., Wohlgemuth, G., Mehta, S., Mueller, M., Zheng, Y., Ogiwara, A., Meissen, J., Showalter, M., Takeuchi, K., Kind, T., Beal, P., Arita, M., & Fiehn, O. (2018). Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics. Nat Methods, 15(1), 53-56. https://doi.org/10.1038/nmeth.4512
Larsen, J. M. (2017). The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology, 151(4), 363-374. https://doi.org/10.1111/imm.12760
Lessey, B. A. (2002). Adhesion molecules and implantation. J Reprod Immunol, 55(1-2), 101-112. https://doi.org/10.1016/s0165-0378(01)00139-5
Li, J., McCormick, J., Bocking, A., & Reid, G. (2012). Importance of vaginal microbes in reproductive health. Reprod Sci, 19(3), 235-242. https://doi.org/10.1177/1933719111418379
Li, M., Ding, Y., Wei, J., Dong, Y., Wang, J., Dai, X., Yan, J., Chu, F., Zhang, K., Meng, F., Ma, J., Zhong, W., Wang, B., Gao, Y., Yang, R., Liu, X., Su, X., & Cao, H. (2024). Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation. Gut Microbes, 16(1), 2377576. https://doi.org/10.1080/19490976.2024.2377576
Li, M., Li, L., Wang, R., Yan, S. M., Ma, X. Y., Jiang, S., Gao, T. Y., Yao, Y., & Li, B. (2019). Prevalence and risk factors for bacterial vaginosis and cervicitis among 511 female workers attending gynecological examination in Changchun, China. Taiwan J Obstet Gynecol, 58(3), 385-389. https://doi.org/10.1016/j.tjog.2018.11.036
Li, X., Zhang, B., Hu, Y., & Zhao, Y. (2021). New Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases. Front Pharmacol, 12, 769501. https://doi.org/10.3389/fphar.2021.769501
Liedig, C., Neupane, P., Lashnits, E., Breitschwerdt, E. B., & Maggi, R. G. (2023). Blood Supplementation Enhances Bartonella henselae Growth and Molecular Detection of Bacterial DNA in Liquid Culture. Microbiol Spectr, 11(3), e0512622. https://doi.org/10.1128/spectrum.05126-22
Lin, H., & Peddada, S. D. (2020). Analysis of compositions of microbiomes with bias correction. Nat Commun, 11(1), 3514. https://doi.org/10.1038/s41467-020-17041-7
Liversedge, N. H., Turner, A., Horner, P. J., Keay, S. D., Jenkins, J. M., & Hull, M. G. (1999). The influence of bacterial vaginosis on in-vitro fertilization and embryo implantation during assisted reproduction treatment. Hum Reprod, 14(9), 2411-2415. https://doi.org/10.1093/humrep/14.9.2411
Lynch, T., Peirano, G., Lloyd, T., Read, R., Carter, J., Chu, A., Shaman, J. A., Jarvis, J. P., Diamond, E., Ijaz, U. Z., & Church, D. (2019). Molecular Diagnosis of Vaginitis: Comparing Quantitative PCR and Microbiome Profiling Approaches to Current Microscopy Scoring. J Clin Microbiol, 57(9). https://doi.org/10.1128/JCM.00300-19
Ma, B., Forney, L. J., & Ravel, J. (2012). Vaginal microbiome: rethinking health and disease. Annu Rev Microbiol, 66, 371-389. https://doi.org/10.1146/annurev-micro-092611-150157
Marro, F. C., Laurent, F., Josse, J., & Blocker, A. J. (2022). Methods to monitor bacterial growth and replicative rates at the single-cell level. FEMS Microbiol Rev, 46(6). https://doi.org/10.1093/femsre/fuac030
Massad, L. S., Daubert, E. M., Evans, C. T., Minkoff, H., Kassaye, S., Dionne-Odom, J., Seidman, D., Murphy, K., Alcaide, M. L., Adimora, A. A., Sheth, A. N., Golub, E. T., French, A. L., & Weber, K. M. (2021). Trends in Bacterial Vaginosis Prevalence in a Cohort of U.S. Women with and at Risk for HIV. J Womens Health (Larchmt). https://doi.org/10.1089/jwh.2021.0102
McEwan, M., Lins, R. J., Munro, S. K., Vincent, Z. L., Ponnampalam, A. P., & Mitchell, M. D. (2009). Cytokine regulation during the formation of the fetal-maternal interface: focus on cell-cell adhesion and remodelling of the extra-cellular matrix. Cytokine Growth Factor Rev, 20(3), 241-249. https://doi.org/10.1016/j.cytogfr.2009.05.004
Melander, R. J., Minvielle, M. J., & Melander, C. (2014). Controlling bacterial behavior with indole-containing natural products and derivatives. Tetrahedron, 70(37), 6363-6372. https://doi.org/10.1016/j.tet.2014.05.089
Miller, E. A., Beasley, D. E., Dunn, R. R., & Archie, E. A. (2016). Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique? Front Microbiol, 7, 1936. https://doi.org/10.3389/fmicb.2016.01936
Mira, N. P., Marshall, R., Pinheiro, M. J. F., Dieckmann, R., Dahouk, S. A., Skroza, N., Rudnicka, K., Lund, P. A., De Biase, D., & Working Group 3 of the, C. A. E. (2024). On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges. Int J Infect Dis, 140, 119-123. https://doi.org/10.1016/j.ijid.2024.01.011
Mladenka, P., Macakova, K., Kujovska Krcmova, L., Javorska, L., Mrstna, K., Carazo, A., Protti, M., Remiao, F., Novakova, L., researchers, O., & collaborators. (2022). Vitamin K - sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutr Rev, 80(4), 677-698. https://doi.org/10.1093/nutrit/nuab061
Moore, D. E., Soules, M. R., Klein, N. A., Fujimoto, V. Y., Agnew, K. J., & Eschenbach, D. A. (2000). Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil Steril, 74(6), 1118-1124. https://doi.org/10.1016/s0015-0282(00)01624-1
Moreno-Gamez, S. (2022). How bacteria navigate varying environments. Science, 378(6622), 845. https://doi.org/10.1126/science.adf4444
Moreno, I., Cicinelli, E., Garcia-Grau, I., Gonzalez-Monfort, M., Bau, D., Vilella, F., De Ziegler, D., Resta, L., Valbuena, D., & Simon, C. (2018). The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol, 218(6), 602 e601-602 e616. https://doi.org/10.1016/j.ajog.2018.02.012
Moreno, I., Codoner, F. M., Vilella, F., Valbuena, D., Martinez-Blanch, J. F., Jimenez-Almazan, J., Alonso, R., Alama, P., Remohi, J., Pellicer, A., Ramon, D., & Simon, C. (2016). Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol, 215(6), 684-703. https://doi.org/10.1016/j.ajog.2016.09.075
Moreno, I., & Franasiak, J. M. (2017). Endometrial microbiota-new player in town. Fertil Steril, 108(1), 32-39. https://doi.org/10.1016/j.fertnstert.2017.05.034
Moreno, I., Garcia-Grau, I., Perez-Villaroya, D., Gonzalez-Monfort, M., Bahçeci, M., Barrionuevo, M. J., Taguchi, S., Puente, E., Dimattina, M., Lim, M. W., Meneghini, G., Aubuchon, M., Leondires, M., Izquierdo, A., Perez-Olgiati, M., Chavez, A., Seethram, K., Bau, D., Gomez, C., Valbuena, D., Vilella, F., & Simon, C. (2021). Endometrial microbiota composition is associated with reproductive outcome in infertile patients. BMJ. https://doi.org/10.1101/2021.02.05.21251207
Morgan, J. (2024). The Role of the Microbiome in Human Implantation. The European Fertility Society C.I.C.
Muzny, C. A., Laniewski, P., Schwebke, J. R., & Herbst-Kralovetz, M. M. (2020). Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis. Curr Opin Infect Dis, 33(1), 59-65. https://doi.org/10.1097/QCO.0000000000000620
Neto, D. P. A., & de Castro Fonseca, M. (2022). Protocol for rapid obtention and fractionation of anaerobic bacterial conditioned media to study calcium signaling in enteroendocrine cells. STAR Protoc, 3(3), 101486. https://doi.org/10.1016/j.xpro.2022.101486
Nikas, G., & Aghajanova, L. (2002). Endometrial pinopodes: some more understanding on human implantation? Reproductive BioMedicine Online, 4, 18-23. https://doi.org/10.1016/s1472-6483(12)60111-4
Nishiyama, K., Sugiyama, M., & Mukai, T. (2016). Adhesion Properties of Lactic Acid Bacteria on Intestinal Mucin. Microorganisms, 4(3). https://doi.org/10.3390/microorganisms4030034
Norwitz, E. R., Schust, D. J., & Fisher, S. J. (2001). Implantation and the survival of early pregnancy. N Engl J Med, 345(19), 1400-1408. https://doi.org/10.1056/NEJMra000763
Nuse, B., Holland, T., Rauh, M., Gerlach, R. G., & Mattner, J. (2023). L-arginine metabolism as pivotal interface of mutual host-microbe interactions in the gut. Gut Microbes, 15(1), 2222961. https://doi.org/10.1080/19490976.2023.2222961
O'Callaghan, J. L., Willner, D., Buttini, M., Huygens, F., & Pelzer, E. S. (2021). Limitations of 16S rRNA Gene Sequencing to Characterize Lactobacillus Species in the Upper Genital Tract. Front Cell Dev Biol, 9, 641921. https://doi.org/10.3389/fcell.2021.641921
Odogwu, N. M., Onebunne, C. A., Chen, J., Ayeni, F. A., Walther-Antonio, M. R. S., Olayemi, O. O., Chia, N., & Omigbodun, A. O. (2021). Lactobacillus crispatus thrives in pregnancy hormonal milieu in a Nigerian patient cohort. Sci Rep, 11(1), 18152. https://doi.org/10.1038/s41598-021-96339-y
Onyango, S., Mi, J. D., Koech, A., Okiro, P., Temmerman, M., von Dadelszen, P., Tribe, R. M., Omuse, G., & Network, P. (2023). Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth. Front Immunol, 14, 1306473. https://doi.org/10.3389/fimmu.2023.1306473
Palm, W., & Thompson, C. B. (2017). Nutrient acquisition strategies of mammalian cells. Nature, 546(7657), 234-242. https://doi.org/10.1038/nature22379
Park, H. J., Kim, Y. S., Yoon, T. K., & Lee, W. S. (2016). Chronic endometritis and infertility. Clin Exp Reprod Med, 43(4), 185-192. https://doi.org/10.5653/cerm.2016.43.4.185
Patel, P., Cossette, C., Anumolu, J. R., Gravel, S., Lesimple, A., Mamer, O. A., Rokach, J., & Powell, W. S. (2008). Structural requirements for activation of the 5-Oxo-6E, 8Z, 11Z, 14Z-eicosatetraenoic acid (5-Oxo-ETE) receptor: Identification of a mead acid metabolite with potent agonist activity. Journal of Pharmacology and Experimental Therapeutics, 325(2), 698-707. https://doi.org/10.1124/jpet.107.134908
Phang, J. M. (2019). Proline Metabolism in Cell Regulation and Cancer Biology: Recent Advances and Hypotheses. Antioxid Redox Signal, 30(4), 635-649. https://doi.org/10.1089/ars.2017.7350
Powell, W. S., & Rokach, J. (2016). 5-Oxo-ETE and Inflammation. Lipoxygenases in Inflammation, 185-210. https://doi.org/10.1007/978-3-319-27766-0_9
Prior, J. C. (2020). Women’s reproductive system as balanced estradiol and progesterone actions—A revolutionary, paradigm-shifting concept in women’s health. Drug Discovery Today: Disease Models, 32, 31-40. https://doi.org/10.1016/j.ddmod.2020.11.005
Putowski, L. T. (2004). Implantation. In L. Martini (Ed.), Encyclopedia of Endocrine Diseases (pp. 761-763). Elsevier. https://doi.org/https://doi.org/10.1016/B0-12-475570-4/00744-7
Qin, L., Chen, W. J., Fu, Y., Tang, J., Yi, H., Li, L., Xu, F. H., Zhang, M. M., Cao, W. C., Huang, D. L., & Lai, C. (2022). Hemin derived iron and nitrogen-doped carbon as a novel heterogeneous electro-Fenton catalyst to efficiently degrade ciprofloxacin. Chemical Engineering Journal, 449. https://doi.org/10.1016/j.cej.2022.137840
Qin, Y., Havulinna, A. S., Liu, Y., Jousilahti, P., Ritchie, S. C., Tokolyi, A., Sanders, J. G., Valsta, L., Brozynska, M., Zhu, Q., Tripathi, A., Vazquez-Baeza, Y., Loomba, R., Cheng, S., Jain, M., Niiranen, T., Lahti, L., Knight, R., Salomaa, V., Inouye, M., & Meric, G. (2022). Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat Genet, 54(2), 134-142. https://doi.org/10.1038/s41588-021-00991-z
Quinn, C. E., & Casper, R. F. (2009). Pinopodes: a questionable role in endometrial receptivity. Hum Reprod Update, 15(2), 229-236. https://doi.org/10.1093/humupd/dmn052
Quinn, K. E., Matson, B. C., Wetendorf, M., & Caron, K. M. (2020). Pinopodes: Recent advancements, current perspectives, and future directions. Mol Cell Endocrinol, 501, 110644. https://doi.org/10.1016/j.mce.2019.110644
Ramanathan, R., & Woodrow, K. (2016). Engineering immunity in the mucosal niche against sexually transmitted infections. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 8(1), 107-122. https://doi.org/10.1002/wnan.1359
Ranjit, E., Raghubanshi, B. R., Maskey, S., & Parajuli, P. (2018). Prevalence of Bacterial Vaginosis and Its Association with Risk Factors among Nonpregnant Women: A Hospital Based Study. Int J Microbiol, 2018, 8349601. https://doi.org/10.1155/2018/8349601
Ravel, J., Brotman, R. M., Gajer, P., Ma, B., Nandy, M., Fadrosh, D. W., Sakamoto, J., Koenig, S. S. K., Fu, L., Zhou, X., Hickey, R. J., Schwebke, J. R., & Forney, L. J. (2013). Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome, 1:29. (http://www.microbiomejournal.com/content/1/1/29)
Ravel, J., Gajer, P., Abdo, Z., Schneider, G. M., Koenig, S. S., McCulle, S. L., Karlebach, S., Gorle, R., Russell, J., Tacket, C. O., Brotman, R. M., Davis, C. C., Ault, K., Peralta, L., & Forney, L. J. (2011). Vaginal microbiome of reproductive-age women. PNAS, 108 Suppl 1, 4680-4687. https://doi.org/10.1073/pnas.1002611107
Ravel, J., Moreno, I., & Simon, C. (2021). Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol, 224(3), 251-257. https://doi.org/10.1016/j.ajog.2020.10.019
Reid, G. (2001). Probiotic agents to protect the urogenital tract against infection. Am J Clin Nutr, 73(2 Suppl), 437S-443S. https://doi.org/10.1093/ajcn/73.2.437s
Ren, L., Peng, C., Hu, X., Han, Y., & Huang, H. (2020). Microbial production of vitamin K2: current status and future prospects. Biotechnol Adv, 39, 107453. https://doi.org/10.1016/j.biotechadv.2019.107453
Riganelli, L., Iebba, V., Piccioni, M., Illuminati, I., Bonfiglio, G., Neroni, B., Calvo, L., Gagliardi, A., Levrero, M., Merlino, L., Mariani, M., Capri, O., Pietrangeli, D., Schippa, S., & Guerrieri, F. (2020). Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility. Front Cell Infect Microbiol, 10, 350. https://doi.org/10.3389/fcimb.2020.00350
Rodriguez Jovita, M., Collins, M. D., Sjoden, B., & Falsen, E. (1999). Characterization of a novel Atopobium isolate from the human vagina: description of Atopobium vaginae sp. nov. Int J Syst Bacteriol, 49 Pt 4, 1573-1576. https://doi.org/10.1099/00207713-49-4-1573
Romero, R., Espinoza, J., & Mazor, M. (2004). Can endometrial infection/inflammation explain implantation failure, spontaneous abortion, and preterm birth after in vitro fertilization? Fertil Steril, 82(4), 799-804. https://doi.org/10.1016/j.fertnstert.2004.05.076
Ronneau, S., Moussa, S., Barbier, T., Conde-Alvarez, R., Zuniga-Ripa, A., Moriyon, I., & Letesson, J. J. (2016). Brucella, nitrogen and virulence. Crit Rev Microbiol, 42(4), 507-525. https://doi.org/10.3109/1040841X.2014.962480
Rudzitis-Auth, J., Becker, M., Scheuer, C., Menger, M. D., & Laschke, M. W. (2022). Indole-3-Carbinol Inhibits the Growth of Endometriotic Lesions by Suppression of Microvascular Network Formation. Nutrients, 14(22). https://doi.org/10.3390/nu14224940
Salleh, N., & Giribabu, N. (2014). Leukemia inhibitory factor: roles in embryo implantation and in nonhormonal contraception. Scientific World Journal, 2014, 201514. https://doi.org/10.1155/2014/201514
Schuh, K., Haussler, S., Sadri, H., Prehn, C., Lintelmann, J., Adamski, J., Koch, C., Frieten, D., Ghaffari, M. H., Dusel, G., & Sauerwein, H. (2024). Author Correction: Blood and adipose tissue steroid metabolomics and mRNA expression of steroidogenic enzymes in periparturient dairy cows differing in body condition. Sci Rep, 14(1), 3841. https://doi.org/10.1038/s41598-024-53305-8
Schwiertz, A. (2016). Microbiota of the Human Body Implication in Health and Disease.
Seli, E., Babayev, E., Collins, S. C., Nemeth, G., & Horvath, T. L. (2014). Minireview: Metabolism of female reproduction: regulatory mechanisms and clinical implications. Mol Endocrinol, 28(6), 790-804. https://doi.org/10.1210/me.2013-1413
Seyedsayamdost, M. R. (2019). Toward a global picture of bacterial secondary metabolism. J Ind Microbiol Biotechnol, 46(3-4), 301-311. https://doi.org/10.1007/s10295-019-02136-y
Sher, D., Segre, D., & Follows, M. J. (2024). Quantitative principles of microbial metabolism shared across scales. Nat Microbiol, 9(8), 1940-1953. https://doi.org/10.1038/s41564-024-01764-0
Sherrard, J. (2019). Evaluation of the BD MAX Vaginal Panel for the detection of vaginal infections in a sexual health service in the UK. Int J STD AIDS, 30(4), 411-414. https://doi.org/10.1177/0956462418815284
Sherrard, J., Wilson, J., Donders, G., Mendling, W., & Jensen, J. S. (2018). 2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge. Int J STD AIDS, 29(13), 1258-1272. https://doi.org/10.1177/0956462418785451
Shipitsyna, E., Roos, A., Datcu, R., Hallen, A., Fredlund, H., Jensen, J. S., Engstrand, L., & Unemo, M. (2013). Composition of the vaginal microbiota in women of reproductive age--sensitive and specific molecular diagnosis of bacterial vaginosis is possible? PLoS One, 8(4), e60670. https://doi.org/10.1371/journal.pone.0060670
Shore, V. H., Wang, T. H., Wang, C. L., Torry, R. J., Caudle, M. R., & Torry, D. S. (1997). Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast. Placenta, 18(8), 657-665. https://doi.org/10.1016/s0143-4004(97)90007-2
Simon, C., Frances, A., Piquette, G. N., el Danasouri, I., Zurawski, G., Dang, W., & Polan, M. L. (1994). Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist. Endocrinology, 134(2), 521-528. https://doi.org/10.1210/endo.134.2.8299552
Simon, C., Martin, J. C., & Pellicer, A. (2000). Paracrine regulators of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol, 14(5), 815-826. https://doi.org/10.1053/beog.2000.0121
Smith, R. L., Soeters, M. R., Wust, R. C. I., & Houtkooper, R. H. (2018). Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr Rev, 39(4), 489-517. https://doi.org/10.1210/er.2017-00211
Spencer, T. E., Burghardt, R. C., Johnson, G. A., & Bazer, F. W. (2004). Conceptus signals for establishment and maintenance of pregnancy. Anim Reprod Sci, 82-83, 537-550. https://doi.org/10.1016/j.anireprosci.2004.04.014
Srinivasan, S., Morgan, M. T., Fiedler, T. L., Djukovic, D., Hoffman, N. G., Raftery, D., Marrazzo, J. M., & Fredricks, D. N. (2015). Metabolic signatures of bacterial vaginosis. mBio, 6(2). https://doi.org/10.1128/mBio.00204-15
Staun-Ram, E., & Shalev, E. (2005). Human trophoblast function during the implantation process. Reprod Biol Endocrinol, 3, 56. https://doi.org/10.1186/1477-7827-3-56
Su, W., Gong, C., Zhong, H., Yang, H., Chen, Y., Wu, X., Jin, J., Xi, H., & Zhao, J. (2024). Vaginal and endometrial microbiome dysbiosis associated with adverse embryo transfer outcomes. Reprod Biol Endocrinol, 22(1), 111. https://doi.org/10.1186/s12958-024-01274-y
Tao, X., Franasiak, J. M., Zhan, Y., Scott, R. T., Rajchel, J., Bedard, J., Newby, R., Scott, R. T., Treff, N. R., & Chu, T. (2017). Characterizing the endometrial microbiome by analyzing the ultra-low bacteria from embryo transfer catheter tips in IVF cycles: Next generation sequencing (NGS) analysis of the 16S ribosomal gene. Human Microbiome Journal, 3, 15-21. https://doi.org/10.1016/j.humic.2017.01.004
Tao, Z., Yuan, H., Liu, M., Liu, Q., Zhang, S., Liu, H., Jiang, Y., Huang, D., & Wang, T. (2023). Yeast Extract: Characteristics, Production, Applications and Future Perspectives. J Microbiol Biotechnol, 33(2), 151-166. https://doi.org/10.4014/jmb.2207.07057
Tennoune, N., Andriamihaja, M., & Blachier, F. (2022). Production of Indole and Indole-Related Compounds by the Intestinal Microbiota and Consequences for the Host: The Good, the Bad, and the Ugly. Microorganisms, 10(5). https://doi.org/10.3390/microorganisms10050930
Theodoridis, G., Gika, H. G., & Wilson, I. D. (2008). LC-MS-based methodology for global metabolite profiling in metabonomics/metabolomics. TrAC Trends in Analytical Chemistry, 27(3), 251-260. https://doi.org/10.1016/j.trac.2008.01.008
Tomas, M. S., Claudia Otero, M., Ocana, V., & Elena Nader-Macias, M. (2004). Production of antimicrobial substances by lactic acid bacteria I: determination of hydrogen peroxide. Methods Mol Biol, 268, 337-346. https://doi.org/10.1385/1-59259-766-1:337
Valsamakis, G., Chrousos, G., & Mastorakos, G. (2019). Stress, female reproduction and pregnancy. Psychoneuroendocrinology, 100, 48-57. https://doi.org/10.1016/j.psyneuen.2018.09.031
Vardanyan, R. S., & Hruby, V. J. (2006). Synthesis of Essential Drugs. Elsevier Science. https://doi.org/https://doi.org/10.1016/B978-0-444-52166-8.X5000-6
Vigano, P., Mangioni, S., Pompei, F., & Chiodo, I. (2003). Maternal-conceptus cross talk--a review. Placenta, 24 Suppl B, S56-61. https://doi.org/10.1016/s0143-4004(03)00137-1
Vitagliano, A., Saccardi, C., Litta, P. S., & Noventa, M. (2017). Chronic endometritis: Really so relevant in repeated IVF failure? Am J Reprod Immunol, 78(6). https://doi.org/10.1111/aji.12758
Wang, C. Y., Tsai, H. L., Syu, J. S., Chen, T. Y., & Su, M. T. (2017). Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion. J Cell Physiol, 232(6), 1467-1477. https://doi.org/10.1002/jcp.25649
Wang, J., Li, Z., Ma, X., Du, L., Jia, Z., Cui, X., Yu, L., Yang, J., Xiao, L., Zhang, B., Fan, H., & Zhao, F. (2021). Translocation of vaginal microbiota is involved in impairment and protection of uterine health. Nat Commun, 12(1), 4191. https://doi.org/10.1038/s41467-021-24516-8
Wang, Q., Wurtz, P., Auro, K., Makinen, V. P., Kangas, A. J., Soininen, P., Tiainen, M., Tynkkynen, T., Jokelainen, J., Santalahti, K., Salmi, M., Blankenberg, S., Zeller, T., Viikari, J., Kahonen, M., Lehtimaki, T., Salomaa, V., Perola, M., Jalkanen, S., Jarvelin, M. R., Raitakari, O. T., Kettunen, J., Lawlor, D. A., & Ala-Korpela, M. (2016). Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence. BMC Med, 14(1), 205. https://doi.org/10.1186/s12916-016-0733-0
Wegmann, T. G., Lin, H., Guilbert, L., & Mosmann, T. R. (1993). Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today, 14(7), 353-356. https://doi.org/10.1016/0167-5699(93)90235-D
Wetendorf, M., & DeMayo, F. J. (2014). Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. Int J Dev Biol, 58(2-4), 95-106. https://doi.org/10.1387/ijdb.140069mw
Wilcox, A. J., Baird, D. D., & Weinberg, C. R. (1999). Time of implantation of the conceptus and loss of pregnancy. N Engl J Med, 340(23), 1796-1799. https://doi.org/10.1056/NEJM199906103402304
Wong, S. C., Chan, C. M., Ma, B. B., Lam, M. Y., Choi, G. C., Au, T. C., Chan, A. S., & Chan, A. T. (2009). Advanced proteomic technologies for cancer biomarker discovery. Expert Rev Proteomics, 6(2), 123-134. https://doi.org/10.1586/epr.09.1
Wu, J., Wang, K., Wang, X., Pang, Y., & Jiang, C. (2021). The role of the gut microbiome and its metabolites in metabolic diseases. Protein Cell, 12(5), 360-373. https://doi.org/10.1007/s13238-020-00814-7
Wu, W. Z., Jing, J. W., Chen, Z. J., Guo, X. Y., & Qu, Y. Y. (2024). Indole signaling enhances biofilm formation and quorum sensing in sequencing biofilm batch reactors. Journal of Environmental Chemical Engineering, 12(3). https://doi.org/10.1016/j.jece.2024.112494
Xiong, Y., Wang, J., Liu, L., Chen, X., Xu, H., Li, T. C., Wang, C. C., & Zhang, S. (2017). Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period. Fertil Steril, 108(2), 269-276 e261. https://doi.org/10.1016/j.fertnstert.2017.06.004
Zhang, X., Gan, M., Li, J., Li, H., Su, M., Tan, D., Wang, S., Jia, M., Zhang, L., & Chen, G. (2020). Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism Mediated by IL4I1. J Agric Food Chem, 68(39), 10678-10684. https://doi.org/10.1021/acs.jafc.0c03735
Zhao, F., Hu, X., & Ying, C. (2023). Advances in Research on the Relationship between Vaginal Microbiota and Adverse Pregnancy Outcomes and Gynecological Diseases. Microorganisms, 11(4). https://doi.org/10.3390/microorganisms11040991
Zygmunt, M., Hahn, D., Miinstedt, K., Bischof, P., & Lang, U. (1998). Invasion of Cytotrophoblastic JEG-3 Cells is Stimulated by hCG In Vitro. Placenta, 19, 587-593. https://doi.org/DOI: 10.1016/s0143-4004(98)90019-4