PMID- 37871386 OWN - NLM STAT- MEDLINE DCOM- 20231121 LR - 20231121 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 267 DP - 2023 Nov 15 TI - Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization. PG - 115616 LID - S0147-6513(23)01120-X [pii] LID - 10.1016/j.ecoenv.2023.115616 [doi] AB - Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-alpha when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI >/= 23 kg/m(2) (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Wang, Yi AU - Wang Y AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Du, Yao-Yao AU - Du YY AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yao, Wen AU - Yao W AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Deng, Tao-Ran AU - Deng TR AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Guo, Na AU - Guo N AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yin, Li AU - Yin L AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yuan, Xiao-Qiong AU - Yuan XQ AD - Center for Reproductive Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Guo, Qing-Chun AU - Guo QC AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Li, Juan AU - Li J AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Liao, Hong-Mei AU - Liao HM AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Qin, Dan-Yu AU - Qin DY AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Li, Yu-Feng AU - Li YF AD - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: tjlyf66@126.com. LA - eng PT - Journal Article DEP - 20231021 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Cytokines) RN - 6O7F7IX66E (phthalic acid) RN - 0 (Tumor Necrosis Factor-alpha) RN - FU2EWB60RT (mono-(2-ethylhexyl)phthalate) RN - 0 (Interleukin-6) SB - IM MH - Pregnancy MH - Female MH - Humans MH - *Cytokines MH - *Tumor Necrosis Factor-alpha MH - Bayes Theorem MH - Cross-Sectional Studies MH - Follicular Fluid MH - Interleukin-6 MH - Fertilization in Vitro OTO - NOTNLM OT - Bayesian kernel machine regression OT - Cytokines OT - Follicular fluid OT - IVF women OT - Inflammation OT - Phthalates COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/10/24 00:41 MHDA- 2023/11/21 06:42 CRDT- 2023/10/23 18:03 PHST- 2023/05/08 00:00 [received] PHST- 2023/10/15 00:00 [revised] PHST- 2023/10/17 00:00 [accepted] PHST- 2023/11/21 06:42 [medline] PHST- 2023/10/24 00:41 [pubmed] PHST- 2023/10/23 18:03 [entrez] AID - S0147-6513(23)01120-X [pii] AID - 10.1016/j.ecoenv.2023.115616 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2023 Nov 15;267:115616. doi: 10.1016/j.ecoenv.2023.115616. Epub 2023 Oct 21.