Complements from the Male Reproductive Tract: A Scoping Review
Abstract
:1. Introduction
2. A Brief Overview of Complement
Complement Component | Organ Expression (Male Reproductive) | Potential Functions in Male Reproductive Tract |
---|---|---|
C1 inhibitor (C1INH) 1,2 | Testis | Inhibition of female genital tract complement |
C1q 1 | Testis | Classical pathway |
C1q-binding protein (C1QBP) 1,2 | Testis | Inhibition of female genital tract complement |
C1r 2 | Testis | Classical pathway |
C1s 1,2 | Testis | Classical pathway |
C2 1,2 | Testis | Classical and lectin pathways |
C3 1,2,3 | Testis, semen | Alternative pathway and complement cascade, modulation of female reproductive immunity, sperm–oocyte interaction |
C4 1,2,3 | Testis, semen | Classical and lectin pathways |
C4-binding protein (C4BP) 1,4 | Testis, epididymis, semen | Inhibition of female genital tract complement, modulation of female reproductive immunity |
C5 1 | Testis | Terminal pathway, immune cell modulation |
C5a receptor 1 (C5aR1) 1 | Testis | Anaphylatoxin receptor, immune cell activation, inflammation |
C5a receptor 2 (C5aR2) 1 | Testis | Anaphylatoxin receptor, immune cell modulation |
C6 1 | Testis | Terminal pathway |
C7 1,5 | Testis, prostate | Terminal pathway |
C8a 1 | Testis | Terminal pathway |
C8b 1,2 | Testis | Terminal pathway |
C8c 1,2 | Testis | Terminal pathway |
C9 1,3 | Testis, semen | Terminal pathway |
CD35 1 | Testis | Inhibition of female genital tract complement, immune modulation |
CD46 1,6,7,8 | Testis, semen | Inhibition of female genital tract complement, immune modulation, sperm–oocyte fusion |
CD55 1,2,7,8 | Testis, prostate, semen | Inhibition of female genital tract complement, immune modulation |
CD59 1,2,3,7,8 | Testis, semen | Inhibition of female genital tract complement |
Complement Factor-H-related protein 3 (CFHR3)8 | Testis | Inhibition of female genital tract complement |
Clusterin (CLU) 1,9 | Testis, epididymis, seminal vesicle | Inhibition of female genital tract complement, sperm capacitation, sperm viability, sperm maturation and development |
Cartilage oligomeric matrix protein (COMP) 1 | Testis | Inhibition of female genital tract complement |
Carboxypeptidase B (CPB) 1 | Testis | Inhibition of anaphylatoxins in female genital tract |
Carboxypeptidase N (CPN) 1 | Testis | Inhibition of anaphylatoxins in female genital tract |
Cub and Sushi Multiple Domains 1 (CSMD1) 1 | Testis | Inhibition of female genital tract complement |
Factor D 1 | Testis | Alternative pathway |
Factor H 1,10 | Testis, epididymis, seminal vesicles, semen | Inhibition of female genital tract complement |
Factor I 1 | Testis | Inhibition of female genital tract complement |
Ficolin 1/2 (FCN1/2) 1 | Testis | Lectin pathway |
MBL-associated serine protease 1/2 (MASP1/2) 1,2 | Testis | Lectin pathway |
Mannose-binding lectin 1/2 (MBL1/2) 1 | Testis | Lectin pathway |
Plasminogen (PLG) 1 | Testis | Inhibition of female genital tract complement |
Properdin 1 | Testis | Alternative pathway |
Pentraxin (PTX3) 1,11 | Testis, prostate, semen | Inhibition of female genital tract complement |
Soluble MBL-associated protein 1/2 (SMAP1/2) 1 | Testis | Inhibition of female genital tract complement |
Sushi domain-containing protein 4 (SUSD4) 1 | Testis | Inhibition of female genital tract complement, may play a role in immune tolerance |
Vitronectin (VTN) 1,12 | Testis, semen | Inhibition of female genital tract complement, may influence acrosome reaction but needs investigation |
Von Willebrand Factor (VWF) 1 | Testis | Inhibition of female genital tract complement |
3. Complement in the Testis
3.1. Sertoli Cells
3.2. Leydig Cells
3.3. Macrophages
3.4. Germ Cells
4. Complement in the Epididymis
5. Complement in the Prostate
6. Complement in the Seminal Vesicles
7. Complement in Semen
7.1. Whole Semen
7.2. Seminal Plasma
7.3. Sperm/Germ Cells
8. Clinical Applications for Complement
8.1. Complement Action in Sperm Health and Fertilization
8.2. Complement Therapeutics in Brief
9. Discussion
- The roles of anaphylatoxin signaling in the gonads;
- Functional investigation into genes affected by robust complement exposure;
- Complement expressed by testicular macrophages;
- The effects of C4BP secreted by epididymal cells on sperm maturation;
- Complement in the healthy prostate;
- The specific function of seminal vesicle-derived Factor H;
- A role for PTX3 in sperm maturation;
- Noncanonical CLU functions in seminal plasma, sperm motility, and fertilization;
- The effects of C4BP on sperm in fertilization and sperm health;
- The function of vitronectin on the acrosome.
10. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
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Drug | Complement Target | Disease | Status |
---|---|---|---|
ACH-5548 | Factor D | Immune-related disease | Phase I |
ALXN1720 | C5/C5a/C5aR1 | Myasthenia gravis | Phase I |
ALXN1820 | Properdin | Sickle cell disease | Phase I |
AMY-101 | C3 | Periodontal inflammation | Phase II |
ANX005 | C1/C1q | Huntington’s disease | Phase II |
ANX007 | C1/C1q | Geographic atrophy | Phase II |
ARGX-117 | C2 | Multifocal motor neuropathy, kidney interactions | Phase I |
Avacincaptad pegol | C5 | Geographic atrophy | FDA-approved |
Avacopan | C5aR1 | Autoantibody vasculitis | FDA-approved |
Avdoralimab | C5/C5a/C5aR1 | Bullous pemphigoid | Phase II |
BCX-9930 | Factor D | Paroxysmal nocturnal hemoglobinuria | Phase I |
BDB-001 | C5/C5a/C5aR1 | COVID-19, hidradenitis suppurativa | Phase II/III |
Berinert | C1r/s, MASP | Hereditary angioedema | FDA-approved |
Cemdisiran | C5/C5a/C5aR1 | Hemolytic uremic syndrome, IgA nephropathy, myasthenia gravis | Phase II |
Cinryze | C1r/s, MASP | Hereditary angioedema | FDA-approved |
CLG561 | Properdin | Geographic atrophy | Phase II |
Crovalimab | C5/C5a/C5aR1 | Paroxysmal nocturnal hemoglobinuria | Phase III |
Danicopan | Factor D | Paroxysmal nocturnal hemoglobinuria | Phase III |
Eclulizumab | C5 | Paroxysmal nocturnal hemoglobinuria, myasthenia gravis, neuromyelitis optica spectrum disorder | FDA-approved |
GT103 | Factor H | Non-small-cell lung cancer | Phase I |
IONIS-FB-liuc | Factor B | IgA nephropathy | Phase II |
Iptacopan | Factor B | Paroxysmal nocturnal hemoglobinuria | FDA-approved |
Iptacopan | Factor B | Paroxysmal nocturnal hemoglobinuria, C3 glomerulopathy, IgA nephropathy | Phase III |
MOR210 | C5/C5a/C5aR1 | Advanced solid tumors | Phase I |
Narsoplimab | MASP2 | Thrombotic microangiopathy | Phase III |
Nomacopan | C5/C5a/C5aR1 | Thrombotic microangiopathy | Phase III |
OCTA-C1-INH | C1s/C1r/MASP | Hereditary angioedema | Phase II |
Pegcetacoplan | C3 | Paroxysmal nocturnal hemoglobinuria | FDA-approved |
Pegcetacoplan injection | C3 | Geographic atrophy | FDA-approved |
Pozelimab | C5 | Protein-losing enteropathy | FDA-approved |
Pozelimab | C5/C5a/C5aR1 | Paroxysmal nocturnal hemoglobinuria | Phase III |
Ravulizumab | C5 | Paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome | FDA-approved |
Ruconest | C1r/s, MASP | Hereditary angioedema | FDA-approved |
Sutimlimab | C1s | Cold agglutinin disease | FDA-approved |
Tesidolumab | C5/C5a/C5aR1 | Paroxysmal nocturnal hemoglobinuria | Phase II |
Vemircopan | Factor D | Paroxysmal nocturnal hemoglobinuria | Phase II |
Vilobelimab | C5/C5a/C5aR1 | COVID-19, hidradenitis suppurativa | Phase III |
Zilucoplan | C5 | Myasthenia gravis | FDA-approved |
Zilucoplan | C5/C5a/C5aR1 | Myasthenia gravis | Phase III |
Zimura | C5/C5a/C5aR1 | Geographic atrophy | Phase III |
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Washburn, R.L. Complements from the Male Reproductive Tract: A Scoping Review. BioMed 2024, 4, 19-38. https://doi.org/10.3390/biomed4010002
Washburn RL. Complements from the Male Reproductive Tract: A Scoping Review. BioMed. 2024; 4(1):19-38. https://doi.org/10.3390/biomed4010002
Chicago/Turabian StyleWashburn, Rachel L. 2024. "Complements from the Male Reproductive Tract: A Scoping Review" BioMed 4, no. 1: 19-38. https://doi.org/10.3390/biomed4010002