Disease relevance of SYCP3

• We tested the hypothesis that mutation of the human testis-specific SYCP3 is associated with human non-obstructive azoospermia [1].

High impact information on SYCP3

• The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility [2].
• A null mutation in the SCP3 gene was generated, and we noted that homozygous mutant males were sterile due to massive apoptotic cell death during meiotic prophase [2].
• The SCP3-deficient male mice failed to form axial/lateral elements and SCs, and the chromosomes in the mutant spermatocytes did not synapse [2].
• Some of these aggregates extruded large oocyte-like cells that expressed oocyte markers, such as zona pellucida, and the meiosis marker, synaptonemal complex protein 3 (SCP3) [3].
• We found that SYCP3, but not SYCP1, aggregates appear in the preleptotene nucleus and some persist up to pachytene [4].

Biological context of SYCP3

• The deduced amino acid sequence of the three novel proteins shows homology to SYCP3, a component of the synaptonemal complex located along the paired chromosomes during meiosis [5].
• INTERPRETATION: We suggest that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein via dominant negative interference [1].
• METHODS: Human SYCP3 was isolated on the basis of homology between mouse Sycp3 cDNA and human genome sequences at the aminoacid level [1].
• Instead, we show they are associated by the dense plate, a SCP3-rich structure that is organized during the first meiotic prophase and that is still present at metaphase I [6].
• We find that the synaptonemal complex protein 3 (SCP3) is a main determinant of axial-element assembly and is required for attachment of this structure to meiotic chromosomes, whereas SCP2 helps shape the in vivo structure of the axial element [7].

Anatomical context of SYCP3

• The mutant protein showed greatly reduced interaction with the wild-type protein in vitro and interfered with SYCP3 fibre formation in cultured cells [1].
• Our findings, in association with those obtained in experimental animals, shows that lack of SYCP3 expression in human testis may have a negative effect on spermatogenesis and male fertility [8].
• Expression of various germ cell markers, such as Vasa, growth differentiation marker 9 and SSEA-1, increased in the clonal cell line, and OLCs showed additionally expression of meiosis-specific markers SCP3 and DMC1 [9].

Associations of SYCP3 with chemical compounds

• Consistent with the fact that sanguinarine accumulation, but not that of morphine, can be induced in opium poppy cell suspension culture by addition of methyl jasmonate to the culture medium, cyp80b1 and bbe1, but not cor1 transcript accumulated in response to elicitor treatment [10].

Other interactions of SYCP3

• We found that addition of recombinant human BMP4 increased the expression of the germ cell-specific markers VASA and SYCP3 during differentiation of hES cells to embryoid bodies (EBs) [11].
• We focused on the localization of the axial/lateral element protein SCP3 and the cohesin subunit STAG3 [6].
• The SYCP3 levels were normalized to expression of the housekeeping phosphoglucomutase 1 gene [8].

Analytical, diagnostic and therapeutic context of SYCP3

• Samples of DNA from 19 azoospermic patients with maturation arrest and 75 normal fertile control men were screened for mutations in the SYCP3 gene by sequence analysis of the gene [1].
• Tissue-specific expression of SYCP3 was analysed by PCR of human cDNA [1].
• INTERVENTION(S): Testicular biopsies for histopathological assessment and analyses of SYCP3 expression level by semiquantitative nested reverse transcription-polymerase chain reaction (RT-PCR) [8].

References