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The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium.

ABSTRACT: Purpose:We aimed to evaluate how matrix metalloproteinases (MMPs) regulate the trophoblast invasion and placentation. Methods:Female rats were divided into the estrous cycle and early pregnancy day groups. Obtained uterine tissues and implantation sites were processed for immunofluorescence and real-time PCR examinations. Results:The mRNA expression of MMP-7 was higher than MMP-2 and MMP-9. Immunofluorescence findings confirmed that MMP-2, MMP-7, and MMP-9 were localized in the endometrial stroma, while MMP-7 was high in glandular and lining epithelial cells throughout the entire estrous cycle. However, their immunolocalizations and mRNA expressions were dramatically changed with the early pregnancy days. The MMP-7 reached very strong immunostaining in the giant trophoblast cells (GTCs), and the cytoplasm of mature and differentiating decidual cells, whereas MMP-2 and MMP-9 were mostly seen in the primary decidual zone (PDZ), GTCs, and the endothelium of blood vessels. Conclusions:All three MMPs seemed likely to be a key mediator of trophoblast invasion into the decidual region as well as angiogenesis during the placentation process. Due to the strong and wide expression of MMP-7 in the mature decidua, it could be suggested that MMP-7 is important for decidual ECM remodeling and it might be used as a new marker of decidual reaction.

SUBMITTER: Hamutoglu R

PROVIDER: S-EPMC7542015 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium.

Hamutoğlu Rasim R Bulut Hüseyin Eray HE Kaloğlu Celal C Önder Ozan O Dağdeviren Tuğba T Aydemir Merve Nur MN Korkmaz Ertan Mahir EM

Reproductive medicine and biology 20200806 4

<h4>Purpose</h4>We aimed to evaluate how matrix metalloproteinases (MMPs) regulate the trophoblast invasion and placentation.<h4>Methods</h4>Female rats were divided into the estrous cycle and early pregnancy day groups. Obtained uterine tissues and implantation sites were processed for immunofluorescence and real-time PCR examinations.<h4>Results</h4>The mRNA expression of MMP-7 was higher than MMP-2 and MMP-9. Immunofluorescence findings confirmed that MMP-2, MMP-7, and MMP-9 were localized in ...[more]

PMID: 33071641

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Project description:Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10(-8) M), medroxyprogesterone acetate (10(-7) M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states.

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Dataset Information

The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium.

Publications

The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium.

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