AUTHOR=Denomme Michelle M., White Carlee R., Gillio-Meina Carolina , MacDonald William A., Deroo Bonnie J., Kidder Gerald M., Mann Mellissa R.

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

JOURNAL=Frontiers in Genetics

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2012.00129

DOI=10.3389/fgene.2012.00129

ISSN=1664-8021

ABSTRACT=<p>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 <italic>de novo</italic> 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, <italic>Snrpn, Peg3</italic>, and <italic>Peg1</italic>. 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 <italic>de novo</italic> methylation acquisition,<italic></italic>individual oocytes from <italic>Esr2-</italic> and <italic>Gja4</italic>-deficient mice were also assessed for DNA methylation establishment. We observed no aberrant or delayed acquisition of DNA methylation at <italic>Snrpn, Peg3</italic>, or <italic>Peg1 </italic>in oocytes from <italic>Esr2-</italic>deficient females, and no perturbation in <italic>Snrpn </italic>or<italic> Peg3</italic><italic>de novo</italic> methylation in oocytes from <italic>Gja4</italic>-null females. However, <italic>Gja4</italic> deficiency resulted in a loss or delay in methylation acquisition at <italic>Peg1</italic>. One explanation for this difference between the three loci analyzed is the late establishment of DNA methylation at the <italic>Peg1 </italic>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.</p>