All Phenotypes Mir202<em1Hncs> MGI Mouse

reproductive system phenotype ( J:338367 )

N	• female fertility is comparable to that of wild-type females in terms of litter size

decreased male germ cell number ( J:338367 )

• at 4 months of age, the number of MVH+ male germ cells per tubule is significantly lower than in wild-type males

• however, the number of WT1+ Sertoli cells per tubule is normal

multinucleated giant male germ cells ( J:338367 )

• at 4 months of age, multinucleated syncytia are observed in the seminiferous tubules

absent chiasmata formation ( J:338367 )

• more chromosomal bivalents lacking MLH1 foci are observed in pachynema-like cells; interstitial CDK2 foci marking incipient crossover sites are largely absent in pachytene spermatocytes

• diplotene spermatocytes show an increased proportion of achiasmate autosomal bivalents, indicating crossover failure

abnormal chromosomal synapsis ( J:338367 )

• an abnormal SYCP3 signal, in the form of bubbles and forks, indicating large-scale asynapsis between homologous chromosomes, is frequently detected in pachynema-like cells

• 84.3% of pachynema-like cells undergo inter-sister synapsis in their autosomes, as indicated by co-localization of SYCP3 and SYCP1 in asynapsed homologs

• 31.6% of pachytene spermatocytes, in which inter-sister synapsis is detected in sex chromosomes, also undergo inter- sister synapsis in the asynapsed regions of the autosomal homologous chromosomes

• co-localization of SYCP3 and SYCP1 on asynapsed chromosomes is detected as early as at zygonema

abnormal synaptonemal complex ( J:338367 )

• triple staining of SYCP3, gammaH2AX, and H1t revealed that many pachytene/diplotene spermatocytes contain chromosome(s) with discontinuous SYCP3 staining, indicating partially formed synaptonemal complex axes and regional asynapsis

• on average, 33.5% of pachynema and 55% of diplonema contain abnormal SYCP3 staining signals versus only about 0.6% in wild-type cells

increased male germ cell apoptosis ( J:338367 )

• at 4 months of age, TUNEL staining showed a significant increase in apoptotic cell number per seminiferous tubule

• co-staining of TUNEL, acrosome, and DAPI identified apoptotic cells as pachytene spermatocytes at stages I-X

seminiferous tubule degeneration ( J:338367 )

• seminiferous tubules contain detached multinucleated syncytia, many vacuoles, and many apoptotic cells with condensed nuclei

small testis ( J:338367 )

• at 4, 8 and 12 months of age, testis/body weight ratio is significantly lower than in wild-type males

• however, body weight is relatively normal

abnormal spermatogenesis ( J:338367 )

• H&E staining of testis sections showed detached multinucleated syncytia and many vacuoles and apoptotic cells, indicating impaired spermatogenesis

• total number of spermatogenic cells and the number of meiotic and post-meiotic cells are significantly lower than those in wild-type males

oligozoospermia ( J:338367 )

• at 4 months of age, caudal epididymal sperm count is significantly lower than in wild-type males

• however, sperm morphology is normal

abnormal male meiosis ( J:338367 )

• multiple processes during meiosis prophase I, including synapsis and crossover formation are disrupted, and inter-sister chromatid synapses are detected

• gammaH2AX signals all disappear in autosomes and still exist in XY body at late pachynema and diplonema, suggesting that DSBs are repaired

• numbers of MLH1 and RAD51 foci, but not those of the DMC1 foci, are reduced in pachynema-like cells

abnormal X-Y chromosome synapsis during male meiosis ( J:338367 )

• 77.6% of pachytene spermatocytes exhibit co-localization of SYCP3 and SYCP1 in X and Y chromosomes beyond the pseudoautosomal region (PAR) versus only 4.3% in wild-type cells, indicating inter-sister synapsis in the XY body

arrest of male meiosis ( J:338367 )

• gammaH2AX staining showed more leptotene/zygotene and fewer pachytene/diplotene spermatocytes in testes, indicating that meiosis is blocked in transition from zygonema to pachynema

decreased litter size ( J:338367 )

• mating of adult males with wild-type females results in a significantly lower number of litters per male compared with wild-type males

reduced male fertility ( J:338367 )

• mating of adult males with wild-type females results in a significantly lower pregnancy rate and litter size compared with wild-type males