Effects of Voltage Gated Sodium Channel Modulator on Development of the Male Mouse Mammary Gland 

Presenter: Bridget Catherine Fleming

Faculty Sponsor: Laura N. Vandenberg

School: UMass Amherst

Research Area: Biology

Session: Poster Session 5, 3:15 PM - 4:00 PM, Auditorium, A59

ABSTRACT

Lamotrigine is a commonly prescribed anti-epileptic that targets ubiquitously expressed voltage gated sodium channels. Previous studies within the lab have investigated lamotrigine and its potential teratogenicity. In this study, pregnant female mice were administered lamotrigine, and the effects of exposure were evaluated on male offspring prior to puberty (postnatal day 21), and at the height of puberty (postnatal day 32-35).  My project aims to quantify the effects of this voltage-gated ion channel modulator on male mammary gland development. Using whole-mounted mammary glands, we have conducted morphological analyses to quantify changes to structures characteristic of different phases of development. My evaluations have specifically focused on variations in ductal area, number of branching points, and number and size of TEBs; these features can reveal the effects of lamotrigine treatment on the growth and complexity of the gland. I have now excised portions of the mammary glands with epithelium and will conduct immunohistochemistry to further analyze patterns in expression of biomarkers that may be affected by early-life exposures to lamotrigine. We anticipate that immunohistopathological analysis will provide more information regarding the molecular mechanism for the effects we have observed. Finally, I will be using QSAR to also make predictions about the hormonal activity of lamotrigine. When completed, this study will help us understand the role of these voltage gated ion channels during mammary gland development and provide insight into the susceptibility of individuals to the drug during early development.