Tomoaki Yoshida1, Kazuhide Takada2, Shihoko Komine-Aizawa3, Yoshimasa Kamei4, Osamu Ishihara4, Satoshi Hayakawa3. 1. Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan; Department of Obstetrics and Gynecology, Saitama Medical University Hospital, Saitama, Japan. 2. Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan. Electronic address: takada.kazuhide@nihon-u.ac.jp. 3. Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan. 4. Department of Obstetrics and Gynecology, Saitama Medical University Hospital, Saitama, Japan.
Abstract
INTRODUCTION: Recent studies have shown that the endometrium possesses unique microbiomes, including Lactobacillus. However, the roles of these microbes are currently unknown, especially in placentation and the early stage of pregnancy. METHODS: The immortalized human first-trimester trophoblast cell line HTR-8/SVneo was cultured in the presence or absence of Lactobacillus crispatus. Invasive and migrative activities were directly evaluated using an optical microscope and a time-lapse imaging system. Protein levels of the invasion-related protein matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 were evaluated using ELISA. RESULTS: Matrigel invasion of HTR-8/SVneo cells was significantly increased by L. crispatus, though migration was not affected. The culture supernatant of L. crispatus also promoted invasion. Additionally, levels of the active forms of MMP-1 and MMP-2 in the cell culture medium were upregulated by L. crispatus treatment, but that of MMP-9 was not changed. DISCUSSION: L. crispatus promotes trophoblast invasion with an increase in MMP-1 and MMP-2 activation. Our results might explain why Lactobacillus dominance in the endometrium seems beneficial for implantation. Nevertheless, further research is required to determine whether the promotion of trophoblast invasion by L. cripatus is favorable for successful placentation at the early stage of pregnancy.
INTRODUCTION: Recent studies have shown that the endometrium possesses unique microbiomes, including Lactobacillus. However, the roles of these microbes are currently unknown, especially in placentation and the early stage of pregnancy. METHODS: The immortalized human first-trimester trophoblast cell line HTR-8/SVneo was cultured in the presence or absence of Lactobacillus crispatus. Invasive and migrative activities were directly evaluated using an optical microscope and a time-lapse imaging system. Protein levels of the invasion-related protein matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 were evaluated using ELISA. RESULTS: Matrigel invasion of HTR-8/SVneo cells was significantly increased by L. crispatus, though migration was not affected. The culture supernatant of L. crispatus also promoted invasion. Additionally, levels of the active forms of MMP-1 and MMP-2 in the cell culture medium were upregulated by L. crispatus treatment, but that of MMP-9 was not changed. DISCUSSION: L. crispatus promotes trophoblast invasion with an increase in MMP-1 and MMP-2 activation. Our results might explain why Lactobacillus dominance in the endometrium seems beneficial for implantation. Nevertheless, further research is required to determine whether the promotion of trophoblast invasion by L. cripatus is favorable for successful placentation at the early stage of pregnancy.
Authors: Martha Heusler; Rebekka Einenkel; Jens Ehrhardt; Damián Oscar Muzzio; Marek Zygmunt Journal: Front Immunol Date: 2021-08-31 Impact factor: 7.561