LGR4 Regulates the Postnatal Development and Integrity of Male Reproductive Tracts in Mice1
| Autor: | Takayuki Hoshii, Kimi Araki, Naomi Nakagata, Motohiro Takeya, Toru Takeo, Ken Ichi Yamamura |
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| Rok vydání: | 2007 |
| Předmět: |
Germinal epithelium
endocrine system medicine.medical_specialty Estrogen receptor Efferent ducts Cell Biology General Medicine Biology medicine.disease Epididymis Male infertility medicine.anatomical_structure Endocrinology Reproductive Medicine Rete testis Internal medicine medicine Male genital duct Sperm motility |
| Zdroj: | Biology of Reproduction. 76:303-313 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod.106.054619 |
| Popis: | The roles of the leucine-rich repeat domain containing G protein-coupled receptor (GPCR) 4 (Lgr4), which is one of the orphan GPCRs, were analyzed with the Lgr4 hypomorphic mutant mouse line (Lgr4 Gt ). This homozygous mutant had only one-tenth the normal transcription level; furthermore, 60% of them survived to adulthood. The homozygous male was infertile, showing morphologic abnormalities in both the testes and the epididymides. In the testes, luminal swelling, loss of germinal epithelium in the seminiferous tubules, and rete testis dilation were observed. Cauda epididymidis sperm were immotile. Rete testis dilation was due to a water reabsorption failure caused by a decreased expression of an estrogen receptor (ESR1) and SLC9A3 in the efferent ducts. Although we found differential regulation of ESR1 expression in the efferent ducts and the epididymis, the role of ESR1 in the epididymis remains unclear. The epididymis contained short and dilated tubules and completely lacked its initial segment. In the caput region, we observed multilamination and distortion of the basement membranes (BMs) with an accumulation of laminin. Rupture of swollen epididymal ducts was observed, leading to an invasion of macrophages into the lumen. Male infertility was probably due to the combination of a developmental defect of the epididymis and the rupture of the epithelium resulting in the immotile spermatozoa. These results indicate that Lgr4 has pivotal roles to play in the regulation of ESR1 expression, the control of duct elongation through BM remodeling, and the regional differentiation of the caput epididymidis. developmental biology, epididymis, estradiol receptor, male reproductive tract, steroid hormone receptors |
| Databáze: | OpenAIRE |
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