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Published on: August 25, 2023
The 24,25(OH)2D3-TLCD3B signaling complex and reproductive function in mice and men
Ireen Kooij1, Katrine Mitrofanov1, Anders Rehfeld2
1Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital, Herlev and Gentofte, Denmark.
Summary
The vitamin D metabolite 24,25(OH)2D3 and its receptor TLCD3B are not essential for male reproductive function in mice. This signaling pathway shows limited impact on human sperm function, highlighting vitamin D signaling complexity.
Area of Science:
- Endocrinology
- Reproductive Biology
- Molecular Biology
Background:
- Vitamin D plays a role in male reproduction.
- CYP24A1, a vitamin D-inactivating enzyme, is expressed in spermatozoa and linked to semen quality.
- The metabolite 24,25(OH)2D3, produced by CYP24A1, activates the TRAM-LAG1-CLN8 domain 3B (TLCD3B) protein.
Purpose of the Study:
- To investigate the role of 24,25(OH)2D3-TLCD3B signaling in male reproductive function.
- To determine the expression of TLCD3B in reproductive tissues and spermatozoa.
- To assess the impact of TLCD3B deficiency and 24,25(OH)2D3 treatment on reproductive parameters.
Main Methods:
- Expression analysis of TLCD3B in mouse and human testis and spermatozoa.
- Reproductive function assessment in global and germ cell-specific TLCD3B-deficient mice.
- Hormonal analysis (LH, inhibin B) in treated and deficient mice.
- In vitro assessment of 24,25(OH)2D3 effects on human spermatozoa.
Main Results:
- TLCD3B is expressed in mouse and human testis and human spermatozoa.
- Short-term 24,25(OH)2D3 treatment in male mice increased LH and inhibin B.
- TLCD3B-deficient mice (global and germ cell-specific) showed no significant changes in reproductive function.
- Female TLCD3B-deficient mice had elevated 1,25(OH)2D3 and reduced ovarian Cyp24a1 expression but normal reproduction.
- High concentrations of 24,25(OH)2D3 induced a rapid Ca2+ increase in human spermatozoa, likely via the vitamin D receptor.
Conclusions:
- The 24,25(OH)2D3-TLCD3B signaling pathway is dispensable for male reproductive function in mice.
- This signaling pathway has limited effects on human spermatozoa, primarily mediated by the vitamin D receptor.
- The study underscores the complexity of vitamin D signaling and the limited importance of 24,25(OH)2D3-TLCD3B in male reproduction in young adult mice.
