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Updated: Aug 8, 2026
Isolation of Leukocytes from the Human Maternal-fetal Interface
Published on: May 21, 2015
Macrophage migration inhibitory factor-nitric oxide interaction in human fetal membranes at term pregnancy
Alessandra Zicari1, Carlo Ticconi, Francesca Ietta
1Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Objectives:
Macrophage migration inhibitory factor (MIF), a multifunctional proinflammatory cytokine, has been recently involved in many aspects of reproduction including pregnancy. However, no evidence is available on the role of MIF in gestational tissues nor on factors regulating MIF production. This study, conducted on explants of human fetal membranes at term gestation, has been undertaken to investigate whether: (1) MIF is produced by fetal membranes; (2) nitric oxide (NO) can regulate local MIF production; and (3) MIF, in turn, can influence NO release in these tissues.
Methods:
Tissues were obtained from 56 healthy women who underwent elective cesarean delivery. Fetal membranes have been incubated with either sodium nitroprusside (NP), a NO donor, or recombinant MIF (r-MIF), or a specific anti-MIF antibody (MIF-Ab). Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA), and colorimetric assay have been used to detect MIF mRNA and protein, inducible nitric oxide synthase (iNOS), and NO metabolites.
Results:
Fetal membranes basally express MIF mRNA and protein and release MIF. Exposing tissues to NP results in an increase of MIF mRNA expression and protein release. Conversely, treatment of tissues with MIF is followed by a reduction in iNOS mRNA and protein expression as well as in NO release. These effects are reversed by adding MIF-Ab.
Conclusions:
MIF is generated and released by human fetal membranes at term. MIF mRNA and protein expression and release are modulated by NO. MIF, in turn, can reduce iNOS expression and NO release by these tissues. NO could be a regulator of MIF production in pregnancy and labor.
Insights
Human fetal membranes produce macrophage migration inhibitory factor (MIF), a key cytokine in reproduction. Nitric oxide (NO) regulates MIF production, and MIF influences NO release, suggesting a role in pregnancy and labor.
Area of Science:
- Reproductive immunology
- Cytokine signaling
- Fetal membrane physiology
Background:
- Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in reproductive processes.
- The role of MIF in gestational tissues and its regulation during pregnancy remain largely unexplored.
Purpose of the Study:
- To investigate MIF production in human fetal membranes at term gestation.
- To determine if nitric oxide (NO) regulates local MIF production.
- To assess MIF's influence on NO release in these tissues.
Main Methods:
- Human term fetal membranes were incubated with a NO donor (sodium nitroprusside), recombinant MIF, or an anti-MIF antibody.
- MIF mRNA and protein, inducible nitric oxide synthase (iNOS), and NO metabolites were quantified using RT-PCR, Western blot, ELISA, and colorimetric assays.
Main Results:
- Fetal membranes constitutively express and release MIF.
- NO donor treatment increased MIF mRNA and protein levels.
- MIF treatment decreased iNOS expression and NO release, effects reversed by anti-MIF antibody.
Conclusions:
- Human fetal membranes at term generate and release MIF.
- NO modulates MIF expression and release.
- MIF reduces iNOS expression and NO release, indicating a regulatory feedback loop.
- NO may regulate MIF production during pregnancy and labor.
