Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

Abstract

The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis.

• Authors: Lan Hai, Deepak S Hiremath, Marilène Paquet, Prema Narayan
• Journal: Biology of reproduction (Biol Reprod) Vol. 96 Issue 5 Pg. 1007-1018 (May 01 2017) ISSN: 1529-7268 [Electronic] United States
• PMID: 28339861 (Publication Type: Journal Article)
• Copyright: © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please [email protected].

Chemical References

• LHCGR protein, mouse
• Receptors, LH
• Estradiol

Topics

• Adenoma (physiopathology)
• Animals
• Ejaculation
• Estradiol (metabolism)
• Genitalia, Male (pathology, physiopathology)
• Infertility, Male (genetics, pathology, physiopathology)
• Leydig Cell Tumor (pathology, physiopathology)
• Male
• Mice
• Penis (pathology)
• Puberty, Precocious (genetics)
• Receptors, LH (genetics)
• Signal Transduction (genetics)
• Sperm Count
• Sperm Motility
• Testicular Neoplasms (pathology, physiopathology)