Iron overload in the peritoneal cavity of women with pelvic endometriosis.
Van Langendonckt A, Casanas-Roux F, Donnez J.
Department of Gynecology, Universite Catholique de Louvain, Brussels, Belgium
OBJECTIVE: To examine the possible involvement of iron in the physiopathology
of endometriosis.DESIGN: Prospective study.SETTING: Department of gynecology in
a university hospital.PATIENT(S): Seventy patients undergoing
laparoscopy.INTERVENTION(S): Collection of peritoneal fluid (n = 57), blood
samples, and biopsy samples from endometrium (n = 62) and from endometriotic (n
= 33) and normal-appearing peritoneum (n = 53).MAIN OUTCOME MEASURE(S):
Measurement of iron and ferritin in serum and peritoneal fluid and staining of
iron deposits with Prussian blue in tissues.RESULT(S): Iron and ferritin
concentrations were significantly higher in the peritoneal fluid of patients
with endometriosis compared with controls during the secretory phase. Higher
rates of ferritin and hemosiderin deposits were observed in the peritoneum
adjacent to red (100%), black (57%), and white (62%) lesions compared with
normal-appearing peritoneum (25%). Deposits were more frequent during the
secretory phase than the proliferative phase in healthy peritoneum from
controls, whereas they were found throughout the cycle in the vicinity of
lesions in patients with endometriosis. Similar rates of iron deposition were
observed in the stroma of black and white lesions and in eutopic endometrium
from patients with endometriosis.CONCLUSION(S): Iron overload was observed in
the cellular and peritoneal fluid compartments of the peritoneal cavity of
women with endometriosis. Iron deposits seem to be related to the presence of
lesions, suggesting that iron may be involved in the pathogenesis of
endometriosis.
Ann Acad Med Stetin 2000;46:63-75 []. [Article in Polish] Skowron J Katedry i Zakladu Histologii i Embriologii Pomorskiej Akademii Medycznej w Szczecinie. [Medline record in process] Excessive activation of macrophages is considered to be the etiological factor of marital infertility. Peritoneal macrophages participate in the phagocytosis of menstrual detritus and sperm in the peritoneal cavity. Iron ingested by peritoneal macrophages could be responsible for their increased spermiophagy. This mechanism would operate in some gynecological diseases, particularly in endometriosis when the ectopic location of endometrial tissue in the pelvic cavity or oviduct becomes a source of cyclic menorrhagia into the peritoneal fluid. The aim of this study was to establish the effect of iron (Jectofer, Astra D, complex salt of Fe+3; 50 micrograms Fe+3/ml) on the morphology and phagocytic activity of LPS-activated peritoneal macrophages. Macrophages were cultured with iron in the presence or absence of iron chelator--Desferal (DFO) (Sigma; 500 micrograms/ml), using the method of Nechala and Hrudka [20]. The viability of cells was evaluated with the trypan blue exclusion test. Cells were washed twice, suspended in modified Dulbecco's medium, supplemented with 2% inactivated fetal calf serum and antibiotics, than transferred (1 x 10(6)) into a culture dish. Nonadherent cells were removed by repeated washing after 1 h incubation at 37 degrees C and 5% CO2. Macrophages were cultured in 1 ml medium with LPS (1 microgram/ml). After 2 or 24 h the macrophages were covered with the same number of rat epididymal sperm cells. Following 1.5 h of incubation, phagocytosis was assessed on the basis of the spermiophagic index (SPI). After 3.5 h of culture macrophages formed monolayers and groups of cells with intersecting sperm tails (Fig. 2). Increased sperm phagocytosis was observed in the macrophage culture exposed to iron for 3.5 h. SPI was significantly higher compared to control value (Fig. 1). The findings were confirmed with scanning and transmission electron microscopy. Macrophages cultured with iron for 3.5 h displayed features of activation, growing to considerable size and developing numerous elongated processes with which they surrounded spermatozoa. The cytoplasm was replete with endosomes containing spermatozoa (Fig. 3). Electron-dense structures could be seen in phagolysosomes. The presence of iron in these structures was confirmed by X-ray microanalysis (Fig. 6). In comparison, macrophages cultured in the presence of iron and iron chelator demonstrated diminished phagocytic activity (Fig. 1). After 24 h of culture macrophages formed cluster-like structures. Spermiophagy was still taking place outside such aggregates and macrophages had a normal appearance (Fig. 4). When iron was added to such culture very few macrophages and spermatozoa could be seen in the electron microscope (Fig. 5A). Iron-loaded macrophages underwent necrosis, their nucleus, plasma membrane and organelles displayed features of degeneration (Fig. 5B). SPI of macrophages exposed to iron for 24 h was significantly decreased as compared with control value (Fig. 1). The ultrastructure of macrophages exposed for 24 h to DFO only was not altered and the phagocytic activity was comparatively higher (Fig. 1). There was a great number of macrophages and spermatozoa forming giant aggregations. The present results suggest that iron enhances spermiophagy in 3.5 h culture. As phagocytic activity of macrophages was reduced by Desferal in 3.5 h culture, an iron chelator could be beneficial in endometriosis to reduce the iron content in the peritoneal cavity where a regular influx of new macrophages takes place. PMID: 11712318, UI: 21569488 _________________________________________________________________ Save the above report in [Macintosh] [Text] format Order documents on this page through Loansome Doc _________________________________________________________________
Fertil Steril 1997 Nov;68(5):826-30
Importance of reactive oxygen species in the peritoneal fluid of women with
endometriosis or idiopathic infertility.
Wang Y, Sharma RK, Falcone T, Goldberg J, Agarwal A
Department of Urology, Cleveland Clinic Foundation, Ohio 44195, USA.
OBJECTIVE: To determine whether reactive oxygen species in peritoneal
fluid might be a factor in infertility. DESIGN: Prospective study.
SETTING: Andrology laboratory and gynecology clinic at a tertiary care
facility. PATIENT(S): Women with endometriosis (n = 15) or idiopathic
infertility (n = 11) who underwent laparoscopy for infertility.
Patients undergoing tubal ligation served as controls (n = 13).
INTERVENTION(S): Aspiration of peritoneal fluid. MAIN OUTCOME
MEASURE(S): Reactive oxygen species levels, presence of
polymorphonuclear granulocytes, and leukocyte distribution in
peritoneal fluid. RESULT(S): Reactive oxygen species were present in
the peritoneal fluid of patients with endometriosis, idiopathic
infertility, and tubal ligation. Levels of reactive oxygen species did
not show a statistically significant difference between patients with
endometriosis and the control group in either unprocessed or processed
(cell-free) peritoneal fluid, but did differ significantly between
patients with idiopathic infertility and controls in processed
peritoneal fluid. Polymorphonuclear granulocytes (> 1 x 10(6)/mL) were
not present in the peritoneal fluid of any patient. Macrophage
concentrations of peritoneal fluid did not differ significantly
between controls and patients with endometriosis or idiopathic
infertility. CONCLUSION(S): Reactive oxygen species in the peritoneal
fluid may not affect fertility directly in women with endometriosis;
however, they may have a role in patients with idiopathic infertility.
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Subject: fertility/iron
J Toxicol Environ Health A 2001 Feb 23;62(4):259-67
In vitro effects of metal ions (Fe2+, Mn2+, Pb2+) on sperm motility and lipid
peroxidation in human semen.
Huang YL, Tseng WC, Lin TH
School of Technology for Medical Sciences, Kaohsiung Medical
University, Taiwan, Republic of China. yelihu@cc.kmu.edu.tw
[Medline record in process]
The effects of divalent manganese ion (Mn2+), ferrous iron (Fe2+), and
lead ion (Pb2+) on human sperm motility and lipid peroxidation were
examined. Human semen from healthy male volunteers was incubated with
0, 5, 50, or 500 ppm divalent metal ions, and the sperm motility was
determined at 0, 2, 4, 6, or 8 h by microscopy. Malondialdehyde (MDA)
levels in seminal plasma was measured by high-performance liquid
chromatography after 8 h of exposure. The results showed that 500 ppm
Mn2+ or Pb2+ significantly inhibited sperm motility without an
accompanying change in seminal MDA levels. Incubation with Fe2+
significantly inhibited sperm motility at 5 ppm, associated with a
marked rise in MDA levels. Our results suggested that Fe2+ may induce
lipid peroxidation to inhibit sperm motility. In the case of Mn2+ and
Pb2+ there is an absence of seminal lipid peroxidation and the
observed inhibition of sperm motility at high concentrations is not
biologically or environmentally relevant.
