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Macrophages and infertility: enhancement of human macrophage-mediated sperm killing by antisperm antibodies
Abstract:
The mechanism by which antisperm antibodies inhibit fertility is not completely understood. Macrophages may play a role in mediating infertility by interacting with sperm and destroying gametes. Experiments were conducted evaluating the effect of antisperm antibody on the phagocytosis and lysis of sperm by human peritoneal macrophages in vitro. Sperm from a fertile man treated with sera from normal men and women or medium alone had 5 to 280 molecules of IgG/sperm, as determined by a 125I-labeled anti-human IgG monoclonal antibody assay. By contrast, sperm treated with sera containing antisperm antibodies had 310 to 1240 molecules of IgG/sperm. Peritoneal macrophages harvested from infertile women with tubal/adhesive problems mediated phagocytosis and lysis of 111In-labeled sperm which was enhanced by treatment of the sperm with sera containing antisperm antibodies (39.0% +/- 1.5% versus 76.3% +/- 3.2% phagocytosis, and 3.3% +/- 0.3% versus 23.3% +/- 2.3% lysis of sperm [control versus antibody-treated]). The likelihood of fertilization in couples with antisperm antibody may be determined not only by the antibody but also by the presence of genital tract macrophages capable of destroying the antibody-coated sperm.
Insights
Antisperm antibodies may cause infertility by enabling macrophages to destroy sperm. This study shows antibodies increase sperm destruction by macrophages, impacting fertilization potential in infertile women.
Area of Science:
- Immunology
- Reproductive Biology
- Cell Biology
Background:
- The precise mechanisms by which antisperm antibodies lead to infertility are not fully elucidated.
- Macrophages are implicated in infertility, potentially by interacting with and destroying gametes.
Purpose of the Study:
- To investigate the role of antisperm antibodies in enhancing the phagocytosis and lysis of sperm by human peritoneal macrophages in vitro.
- To evaluate the impact of antisperm antibodies on sperm-macrophage interactions in the context of female infertility.
Main Methods:
- Quantification of immunoglobulin G (IgG) on sperm treated with normal or antisperm antibody sera using a radioimmunoassay.
- Assessment of sperm phagocytosis and lysis by human peritoneal macrophages from infertile women using 111In-labeled sperm.
- Comparison of macrophage activity on sperm treated with control sera versus sera containing antisperm antibodies.
Main Results:
- Sperm treated with antisperm antibody sera showed significantly higher IgG deposition (310-1240 molecules/sperm) compared to control sera (5-280 molecules/sperm).
- Peritoneal macrophages from infertile women demonstrated enhanced phagocytosis (76.3% vs. 39.0%) and lysis (23.3% vs. 3.3%) of sperm coated with antisperm antibodies.
- These findings indicate a synergistic effect between antisperm antibodies and macrophage activity in impairing sperm function.
Conclusions:
- Antisperm antibodies enhance the destructive capacity of peritoneal macrophages towards sperm.
- The presence and activity of genital tract macrophages may be a critical factor in determining fertility outcomes in couples with antisperm antibodies.
- This interaction provides a potential mechanism for antibody-mediated infertility.