Table 1. The abnormal DNA methylation and related diseases.

Stage	Disease	Aetiology	Species	Reference
Embryogenesis Spermatogenesis	Non-obstructive azoospermia	Hypermethylation at the promoter region of a MTHFR can down-regulate the MTHFR expression and, as a consequence, reduce its enzymatic activity	Human	Khazamipouret al.[57]
	Azoospermia	Disruption of Dnmt3L in testes results in progressive loss of spermatogonia and further causes complete azoospermia	mouse	Bourc’hiset al.[68]
	A greatly reduced number of spermatocytes and methylation loss of paternally imprinted genes	Knockout the Dnmt3a	mouse	Kaneda et al.[64] La Salle et al.[65]
	Idiopathic infertility	Hypermethylation of the MTHFR genes or the MEST imprinted gene	Human	Wu et al.[58]Eroglu and Layman[54] Karaca et al.[59]
	Idiopathic asthenospermia Testicular germ-cell tumour	hypermethylation of VDAC2 promoter region might reduce sperm motility, ultimately result in idiopathic asthenospermia Hypermethylation of regulatory regions of promoters, associated with the silencing tumour suppressor genes	Human Human	Xu et al.[60] Dada et al.[61]
	Testicular cancer	Specific hypermethylation events in the CpG islands of genes associated with piRNAs, which leads to their transcriptional inactivation	Human	Ferreira et al.[56]
	Retarded gestational growth and failure to result in viable offspring	Dnmt1 knockout or loss of function mutations in mice decreases the methylation marks globally in embryos, which leads to the expression of biallelic imprinted genes and retrotransposons, and halts the chromosome inactivation	Mouse	Jenkins and Carrell[4]
	Embryonal carcinoma	High expression of DNMT3A, 3B and 3L	Human	Almstrup et al.[67]
	Fragile X syndrome	Expansion and methylation of the CGG repeat in FMR15′UTR, promoter for the methylation	Human	Verdyck et al.[62] Zhou et al.[63]
Birth	Beckwith–Wiedemann syndrome	Hypermethylation of the H19-DMR and/or hypomethylation of the KvDMR1	Human	Cooper et al.[55]
	Silver–Russell Syndrome	Hypomethylation on the paternal allele of the H19-DMR or hypermethylated at the MEST imprinted gene	Human	Eroglu and Layman[54]