Immunization of male bonnet monkeys (M. radiata) with a recombinant FSH receptor preparation affects testicular function and fertility
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Published on: February 6, 2012
N R Moudgal1, M R Sairam, H N Krishnamurthy
1Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore.
Abstract:
Immunization of proven fertile adult male monkeys (n=3) with a recombinant FSH receptor protein preparation (oFSHR-P) (representing amino acids 1-134 of the extracellular domain of the receptor Mr approximately 15KDa) resulted in production of receptor blocking antibodies. The ability of the antibody to bind a particulate FSH receptor preparation and receptors in intact granulosa cells was markedly (by 30-80%) inhibited by FSH. Serum T levels and LH receptor function following immunization remained unchanged. The immunized monkeys showed a 50% reduction (p<0.001) in transformation of spermatogonia(2C) to primary spermatocytes (4C) as determined by flow cytometry and the 4C:2C ratio showed a correlative change (R 0.81, p<0.0007) with reduction in fertility index (sperm counts X motility score). Breeding studies indicated that monkeys became infertile between 242-368 days of immunization when the fertility index was in the range of 123+/-76 to 354+/-42 (compared to a value of 1602+/-384 on day 0). As the effects observed are near identical to that seen following immunization with FSH it is suggestive that oFSHR-P can substitute for FSH in the development of a contraceptive vaccine.
Insights
Immunizing male monkeys with a FSH receptor protein induced blocking antibodies, leading to infertility. This suggests the FSH receptor protein can be used to develop a contraceptive vaccine.
Area of Science:
- Reproductive biology
- Immunology
- Contraceptive development
Background:
- Follicle-stimulating hormone (FSH) is crucial for spermatogenesis.
- Targeting the FSH receptor is a potential strategy for male contraception.
Purpose of the Study:
- To evaluate the contraceptive potential of a recombinant FSH receptor protein preparation (oFSHR-P).
- To assess the immunogenicity and effects of oFSHR-P immunization in adult male monkeys.
Main Methods:
- Adult male monkeys were immunized with oFSHR-P.
- Antibody production, FSH receptor binding inhibition, serum testosterone, LH receptor function, spermatogenesis, and fertility were assessed.
- Flow cytometry and breeding studies were conducted.
Main Results:
- Immunization with oFSHR-P generated receptor-blocking antibodies that were inhibited by FSH.
- A 50% reduction in spermatogonia to primary spermatocyte transformation was observed.
- Monkeys became infertile between 242-368 days post-immunization.
Conclusions:
- Recombinant FSH receptor protein (oFSHR-P) can induce an immune response leading to reversible infertility in male monkeys.
- oFSHR-P shows promise as a component of a novel contraceptive vaccine, mimicking effects of FSH immunization.
