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. 2012 Jul 11:3:129.
doi: 10.3389/fgene.2012.00129. eCollection 2012.

Compromised fertility disrupts Peg1 but not Snrpn and Peg3 imprinted methylation acquisition in mouse oocytes

Michelle M Denomme  1 , Carlee R White, Carolina Gillio-Meina, William A Macdonald, Bonnie J Deroo, Gerald M Kidder, Mellissa R W Mann
Affiliations

Compromised fertility disrupts Peg1 but not Snrpn and Peg3 imprinted methylation acquisition in mouse oocytes

Michelle M Denomme et al. Front Genet. .

Abstract

Growth and maturation of healthy oocytes within follicles requires bidirectional signaling and intercellular gap junctional communication. Aberrant endocrine signaling and loss of gap junctional communication between the oocyte and granulosa cells leads to compromised folliculogenesis, oocyte maturation, and oocyte competency, consequently impairing fertility. Given that oocyte-specific DNA methylation establishment at imprinted genes occurs during this growth phase, we determined whether compromised endocrine signaling and gap junctional communication would disrupt de novo methylation acquisition using ERβ and connexin37 genetic models. To compare mutant oocytes to control oocytes, DNA methylation acquisition was first examined in individual, 20-80 μm control oocytes at three imprinted genes, Snrpn, Peg3, and Peg1. We observed that each gene has its own size-dependent acquisition kinetics, similar to previous studies. To determine whether compromised endocrine signaling and gap junctional communication disrupted de novo methylation acquisition,individual oocytes from Esr2- and Gja4-deficient mice were also assessed for DNA methylation establishment. We observed no aberrant or delayed acquisition of DNA methylation at Snrpn, Peg3, or Peg1 in oocytes from Esr2-deficient females, and no perturbation in Snrpn or Peg3de novo methylation in oocytes from Gja4-null females. However, Gja4 deficiency resulted in a loss or delay in methylation acquisition at Peg1. One explanation for this difference between the three loci analyzed is the late establishment of DNA methylation at the Peg1 gene. These results indicate that compromised fertility though impaired intercellular communication can lead to imprinting acquisition errors. Further studies are required to determine the effects of subfertility/infertility originating from impaired signaling and intercellular communication during oogenesis on imprint maintenance during preimplantation development.

Keywords: DNA methylation; connexin37; estrogen receptor beta; genomic imprinting; imprint acquisition; infertility; oocyte; oocyte diameter.

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Figures

FIGURE 1
FIGURE 1
Methylation analysis of the Snrpn ICR in individual oocytes derived from control C57BL/6 female mice. The Snrpn ICR region analyzed contains 16 CpGs. Black circles indicate methylated CpGs while white circles indicate unmethylated CpGs. Each row represents an individual oocyte (designation indicated to the left). Methylation percentage and diameter for each oocyte is shown at the right. Oocytes are grouped into cohorts ranging from 20 to 80 μm diameters in 5 μm increments. Oocytes with one methylation pattern represent one of the two parental alleles detected. Oocytes with two methylation patterns represent detection of both parental alleles.
FIGURE 2
FIGURE 2
Methylation percentage of each parental allele at the Snrpn ICR in relation to oocyte diameter (μm). For oocytes with two parental alleles, each allele was graphed separately. Blue diamonds represent oocytes from control females, red circles represent oocytes from Esr2–/– females, and green triangles represent oocytes from Gja4–/– females.
FIGURE 3
FIGURE 3
Methylation analysis of the Peg3 DMR in individual oocytes derived from control C57BL/6 females. The Peg3 DMR region analyzed contains 23 CpGs. Details are described in Figure 1.
FIGURE 4
FIGURE 4
Methylation percentage of each parental allele at the Peg3 DMR in relation to oocyte diameter (μm). Oocytes from control females, Esr2–/– females and Gja4–/– females are represented by blue diamonds, red circles and green triangles, respectively.
FIGURE 5
FIGURE 5
Methylation analysis of the Peg1 DMR in individual oocytes derived from the control C57BL/6 mice. The Peg1 DMR region analyzed contains 15 CpGs. Details are described in Figure 1.
FIGURE 6
FIGURE 6
Methylation percentage of each parental allele at the Peg1 DMR in relation to oocyte diameter (μm). Oocytes from control females, Esr2–/– females and Gja4–/– females are represented by blue diamonds, red circles and green triangles, respectively.
FIGURE 7
FIGURE 7
Methylation analysis of the Snrpn ICR in individual oocytes derived from Esr2–/– females. Details are described in Figure 1.
FIGURE 8
FIGURE 8
Methylation analysis of the Peg3 DMR in individual oocytes derived from Esr2–/– mice. Details are described in Figure 1.
FIGURE 9
FIGURE 9
Methylation analysis of the Peg1 DMR individual oocytes derived from Esr2–/– female mice. Details are described in Figure 1.
FIGURE 10
FIGURE 10
Methylation analysis of the Snrpn ICR in individual oocytes derived from Gja4–/– mice. Details are described in Figure 1.
FIGURE 11
FIGURE 11
Methylation analysis of the Peg3 DMR individual GV oocytes derived from Gja4–/– female mice. Details are described in Figure 1.
FIGURE 12
FIGURE 12
Methylation analysis of the Peg1 DMR individual GV oocytes derived from Gja4–/– females. Details are described in Figure 1.
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