Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Investigating the potential for anti-LHCGR antibodies to provide a castrative/contraceptive effect (#438)

Alexander Cunningham 1 , Laura Lindsay 1 , Margot L Day 1 , Samson Dowland 1
  1. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia

Castration of mammals is currently the most effective method of preventing gamete and hormone production and male sex hormone-driven behaviours. This surgical approach is predominantly used in domestic animals and livestock; however, these are high-cost procedures with associated surgical risks. An alternative in some livestock species is immunocontraception. Male gamete production is reliant on testosterone, which is synthesised in the interstitial cells of Leydig, within the testes. The luteinising hormone/chorionic gonadotrophin receptor (LHCGR) is a cell surface receptor present on Leydig cells responsible for stimulation of steroidogenesis. Being outside the blood testes barrier makes Leydig cells a viable target for a novel non-invasive castrative/contraceptive technique. This study aims to assess the ability for anti-LHCGR antibodies to achieve an immunocontraceptive effect by targeting the Leydig cell population.

Quackenbush Swiss mice were administered with one of three anti-LHCGR antibodies via intraperitoneal injection, controls were injected with saline. After 14 days orchiectomy was performed and testes were fixed for subsequent analysis. Sperm was harvested from fresh epididymis and ductus deferens. Sperm suspension was smeared on a microscope slide and stained with haematoxylin and eosin for analysis of sperm morphology.

Treatment with anti-LHCGR antibodies caused malformation of sperm heads including acrosome defects, decapacitation and alterations in sperm head size. All three anti-LHCGR antibodies caused a reduction of normal sperm head morphology compared to controls. Suggesting that the antibodies may partially impact the spermatogenesis process.

Binding of anti-LHCGR antibodies to Leydig cells may reduce steroid hormone production, which would in-turn impede Sertoli cell support of spermatogenesis. In conclusion, treatment with anti-LHCGR antibodies offers a potential approach in the development of an immunocontraceptive as an alternative to surgical castrative methods.