PMID- 34914313
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20231031
IS  - 1009-3591 (Print)
IS  - 1009-3591 (Linking)
VI  - 27
IP  - 5
DP  - 2021 May
TI  - [Epigenetic regulation for spermatogenic dysfunction-related infertility in 
      C57BL/6J male mice: An experimental study].
PG  - 394-402
AB  - OBJECTIVE: To investigate the effect of epigenetic regulation on spermatogenic 
      dysfunction-related infertility (SDI) in C57BL/6J male mice. METHODS: Sixty 
      C57BL/6J male mice were randomly divided into a normal control and an SDI model 
      group and the SDI model was established using the epididymis-targeting 
      polypeptide CSA combined with indocyanine green-loaded free nanoparticles 
      (ICG-NPS), busufan and dimethyl sulfoxide (DSMO). After intervention with 
      5-AZA-DC, the epididymides were collected from the mice for measurement of the 
      rates of sperm DNA fragmentation (SDF), sperm acrosome integrity (SAI) and 
      spontaneous acrosome reaction (SAR), amplification of the ERp29 gene by FISH, 
      determination of the mRNA and protein expressions of DNMT1, ERp29, PTEN and TSC2 
      by quantitative real-time PCR and Western blot, and analysis of the ERp29, PTEN 
      and TSC2 genes by methylated DNA immunoprecipitation sequencing (MeDIP-seq). 
      RESULTS: After 5-AZA-DC intervention, statistically significant differences were 
      observed between the normal control and the SDI model groups in the rates of SDF 
      (［15.67 +/- 1.33］% vs ［30.15 +/- 2.87］%, P < 0.05) and SAI (［65.33 +/- 7.14］% vs ［47.16 
      +/- 3.45］%, P < 0.05), but not SAR (［11.52 +/- 2.31］% vs ［11.48 +/- 2.27］%, P > 0.05). 
      FISH confirmed evident amplification of the ERp29 gene in the SDI model but not 
      in the normal control group. Compared with the baseline, the SDI model mice 
      showed significant decreases after intervention in the mRNA and protein 
      expressions of DNMT1 (［9.33 +/- 1.15］ vs ［7.01 +/- 1.14］, P < 0.05; ［15.66 +/- 1.45］ vs 
      ［12.33 +/- 1.27］, P < 0.05), but increases in those of ERp29 (［3.04 +/- 1.13］ vs 
      ［6.54 +/- 1.18］, P < 0.05; ［4.37 +/- 1.02］ vs ［6.95 +/- 1.03］, P < 0.05), PTEN (［3.25 +/- 
      1.01］ vs ［5.85 +/- 1.04］, P < 0.05; ［3.54 +/- 1.01］ vs ［5.17 +/- 1.02］, P < 0.05) and 
      TSC2 (［4.27 +/- 1.16］ vs ［6.98 +/- 1.13］, P < 0.05; ［3.83 +/- 1.12］ vs ［6.98 +/- 1.13］, P 
      < 0.05). No statistically significant differences, however, were found in the 
      above parameters in the normal control group before and after intervention (P > 
      0.05). MeDIP-seq manifested 18 significantly differential genes were highly 
      expressed and another 25 lowly expressed in the epididymal tissue of the model 
      mice, all the former 18 down-regulated and all the latter 25 up-regulated after 
      intervention, particularly ERp29, PTEN and TSC2. But there were no statistically 
      significant differences in the expressions of the above genes in the control 
      group (P > 0.05). MeDIP-seq also showed significant differences in the regional 
      methylation levels of the Erp29, PTEN and TSC2 promoters in the epididymal tissue 
      of the model mice (P < 0.05), but not in that of the normal controls after 
      intervention (P > 0.05). CONCLUSIONS: A stable and efficient animal model 
      provided valuable experimental evidence for the diagnosis and treatment of 
      spermatogenic dysfunction-related infertility. ERp29 is an important gene 
      involved in infertility and can be used as a potential target for epigenetic 
      regulation in the treatment of infertility.
FAU - DU, Peng
AU  - DU P
AD  - Department of Reproductive Health and Infertility, Guangdong Maternal and Child 
      Health Hospital, Guangzhou, Guangdong 510010, China.
FAU - Zhang, Xiao-Li
AU  - Zhang XL
AD  - Center of Perinatal Medicine, Huadu Hospital Affiliated to Southern Medical 
      University, Guangzhou, Guangdong 510800, China.
FAU - Zhao, Xiao-Yong
AU  - Zhao XY
AD  - Center of Perinatal Medicine, Huadu Hospital Affiliated to Southern Medical 
      University, Guangzhou, Guangdong 510800, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Nan Ke Xue
JT  - Zhonghua nan ke xue = National journal of andrology
JID - 101093592
SB  - IM
MH  - Animals
MH  - *Epigenesis, Genetic
MH  - *Infertility
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Animal
OTO - NOTNLM
OT  - animal model
OT  - experimental study； mouse
OT  - infertility
OT  - spermatogenic dysfunction
OT  - epigenetic regulation
EDAT- 2021/12/17 06:00
MHDA- 2021/12/21 06:00
CRDT- 2021/12/16 12:44
PHST- 2021/12/16 12:44 [entrez]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PST - ppublish
SO  - Zhonghua Nan Ke Xue. 2021 May;27(5):394-402.