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Insulin receptor substrate 2 is required for testicular development.
Richard J Griffeth1, Jose Carretero, Deborah J Burks
1Centro de Investigación Príncipe Felipe, Valencia, Spain.
Plos One
|June 7, 2013
Summary
Insulin receptor substrate 2 (IRS2) is crucial for male reproductive development. IRS2 deficiency in mice significantly reduces testicular weight and sperm count, highlighting its role in fertility.
Area of Science:
- Reproductive biology
- Endocrinology
- Developmental biology
Background:
- Insulin receptor substrate (IRS) proteins mediate insulin and IGF signaling.
- IRS1 deficiency causes growth retardation and longevity, while IRS2 deficiency leads to diabetes and infertility.
- The role of IRS proteins in male fertility is largely unknown.
Purpose of the Study:
- To investigate the role of IRS proteins, specifically IRS1 and IRS2, in male reproductive organ development and function.
- To determine if IRS2 deficiency impacts testicular weight, cellular composition, and sperm count.
Main Methods:
- Comparison of testicular weight and histology in Irs1-deficient and Irs2-deficient mice versus controls.
- Assessment of Leydig cell number and serum testosterone levels.
- Evaluation of sperm count in epididymides.
Main Results:
- Irs2-deficient mice exhibited a 45% reduction in testis weight compared to controls.
- Reduced testicular weight in Irs2(-/-) mice was associated with fewer Sertoli cells, spermatogonia, spermatocytes, and epididymal spermatozoa.
- Leydig cell number and serum testosterone levels were unaffected by Irs2 deficiency.
Conclusions:
- IRS2 plays a critical role in testicular development, independent of its effects on glucose homeostasis.
- IGF1 signaling mediated by IRS2 is likely essential during embryonic and early postnatal development for normal testicular growth.
- IRS2 deficiency significantly impairs male reproductive organ development and sperm production.
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