Phenotypes for Ppp4c Tg(Stra8-icre)1Reb MGI:7281440 MGI Mouse

abnormal sperm midpiece morphology ( J:309155 )

• tail bending (head-bent-back) is consistently observed in the midpiece of the sperm tail

• cytoplasmic remnants are attached to the midpiece

• however, mitochondrial sheath assembly is normal

kinked sperm flagellum ( J:309155 )

• ~91% of spermatozoa in the testes and cauda epididymis exhibit abnormal tail bending (head-bent-back)

• bending sites are always observed in the midpiece of the tail, not in the head or principal piece

• TEM analysis showed that the tail bent at the midpiece is held together by tissues resembling remnants of cytoplasm

oligozoospermia ( J:309155 )

• at 2 months of age, the total number of sperm in the cauda epididymes is decreased by ~50% relative to that in controls males

abnormal spermatocyte morphology ( J:309155 )

• TUNEL staining showed significant spermatocyte cell loss in the seminiferous epithelium

• however, spermatogonia cell survival is normal

increased male germ cell apoptosis ( J:309155 )

• TUNEL staining showed a significant increase in the number of apoptotic cells in the testes relative to control males

• TUNEL+ signals are colocalized with the spermatocyte cell marker synaptonemal complex protein-3 (SYCP3), but not with the spermatogonia cell marker ZBTB16 (aka PLZF), indicating spermatocyte cell loss in the seminiferous epithelium

decreased sperm progressive motility ( J:309155 )

• at 2 months of age, the percentage of progressive sperm is markedly reduced

asthenozoospermia ( J:309155 )

• at 2 months of age, the percentage of motile sperm is markedly reduced

abnormal seminiferous tubule morphology ( J:309155 )

• some seminiferous tubules appear disorganized with large vacuoles while others show normal tubule structure in histology

small testis ( J:309155 )

• at 2 months of age, testes size is significantly smaller than in control males

decreased testis weight ( J:309155 )

• however, adult body weight is normal

• weight of adult testes is significantly lower than in control males

arrest of spermiogenesis ( J:309155 )

• cytoplasmic remnants are abnormally retained on the bent midpiece, indicating a defect in cytoplasm removal from elongated spermatids which in turn leads to the failure of spermiogenesis

• however, many aspects of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheath arrangement and 9 + 2 flagellar structure assembly, are normal

male infertility ( J:309155 )

• when mated with wild-type females, adult male mice do not produce any progeny despite normal vaginal plug formation

• male infertility can be overcome by intracytoplasmic injection-embryo transfer (ICSI-ET) but male offspring is sub-fertile

impaired fertilization ( J:309155 )

• although tail-bending spermatozoa are found in the vaginal plug after natural mating, no sperm are found in COCs of oviductal ampullae and no two pronuclei formation is observed

• in an IVF assay, the number of spermatozoa bound to the zona pellucida is significantly decreased and sperm fail to fertilize the eggs and develop to the 2-cell stage

decreased fertilization frequency ( J:309155 )

• spermatozoa fail to fertilize eggs by natural mating or IVF

impaired binding of sperm to zona pellucida ( J:309155 )

• the number of spermatozoa bound to the zona pellucida of metaphase II oocytes is significantly decreased after IVF