All Phenotypes Tmem225<em1Jliu> MGI Mouse

reproductive system phenotype ( J:345843 )

N	• male homozygotes show no significant differences in testis and epididymis morphology, testis-to-body weight ratio, spermatogenesis, cauda epididymal sperm count, acrosome formation or progesterone-induced acrosome reaction relative to heterozygous controls

abnormal sperm flagellum morphology ( J:345843 )

• sperm flagella bend gradually to form a hairpin structure during movement from the caput to the cauda of the epididymis; only 15.2% of cauda epididymal sperm flagella are normal

• cauda epididymal sperm show significantly lower protein levels of PPP3R2 [protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II)] and AK1 (adenylate kinase 1), which are associated with sperm flagellum bending

• however, sperm head morphology and the 9 + 2 microtubule structure in the principal piece are intact

abnormal sperm midpiece morphology ( J:345843 )

• immunofluorescence analysis showed that HK1 (hexokinase 1), which catalyzes the first step of glycolysis, shows a stronger positive signal in the sperm midpiece than in the principal piece

• PGK2 (phosphoglycerate kinase 2), which catalyzes the first step of ATP production, is discontinuously positioned in the midpiece

• overall, the relative protein expression level of HK1 is increased, while the protein expression level of PGK2 is reduced

hairpin sperm flagellum ( J:345843 )

• 65.5% of cauda epididymal sperm show an abnormal hairpin-loop configuration with a flagellar bending angle of 180 degrees

• however, no significant increase in the % of hairpin flagella is noted in the corpus epididymis

kinked sperm flagellum ( J:345843 )

• although sperm morphology is normal in the caput epididymis, the % of V-shaped sperm flagella with a bending angle less than 180 degrees is increased both in the corpus and in the cauda

• 19.3% of cauda epididymal sperm exhibit V-shaped sperm flagella

abnormal spermiogenesis ( J:345843 )

• sperm exhibit abnormalities during epididymal maturation

male infertility ( J:345843 )

• male homozygotes fail to produce pups when mated with wild-type females for a period of 6 months

• however, the number of female mice found with vaginal plugs within 15 days of mating is normal

abnormal sperm physiology ( J:345843 )

• cauda epididymal sperm show abnormal protein expression of two key enzymes involved in glycolysis (HK1 and PGK2) and a significantly lower ATP level than control sperm

• protein levels of GPX4 (glutathione peroxidase 4) and TXNRD1 (thioredoxin reductase 1), which are associated with inhibiting ROS production, are significantly lower than those in control cauda sperm

• cauda sperm show a significant increase in intracellular reactive oxygen species (ROS) levels and Ca² concentration, and a significantly lower mitochondrial membrane potential than control sperm, indicating mitochondrial dysfunction

• however, the membrane structure and morphology of sperm mitochondria are normal

decreased sperm progressive motility ( J:345843 )

asthenozoospermia ( J:345843 )

• motility trajectories of cauda epididymal spermatozoa show a significant reduction in the proportions of motile sperm and progressive sperm

• VAP (average path velocity), VSL (straight-line velocity) and VCL (curvilinear velocity) are significantly lower than in control sperm

decreased cellular ATP level ( J:345843 )

• cauda epididymal sperm show a significantly lower ATP level than control sperm