SWHR Emerging Scholars in Women’s Health Research Awardee
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Rachel Gilfarb received her Bachelor of Arts degree from Vanderbilt University in 2018, where she majored in Neuroscience and minored in Women’s and Gender Studies. Currently, she is a PhD candidate at The Ohio State University in the lab of Dr. Benedetta Leuner. Her thesis work examines how adolescent hormonal contraceptive administration in female rats affects the development of the prefrontal cortex. Following her thesis defense in July 2024, she plans to pursue a career in science communication.

 

Abstract: Adolescent Hormonal Contraceptive Administration Impacts Prefrontal Cortex Maturation and Risk-assessment in Female Rats 

Rachel Gilfarb [1], Sanjana Ranade [1], Abby Biddle [1], Marrisa Smail [1], Meredith Stewart [1], Abhishek Rajesh1, Elizabeth Dybas [1], Courtney Dye [1], Kathryn M. Lenz [1], Benedetta Leuner [1].  

[1] The Ohio State University  

Millions of individuals take hormonal contraceptives (HCs) often starting at adolescence when ovarian hormones have important effects on prefrontal cortex (PFC) maturation. Yet, there is a fundamental lack of information about the consequences of hormonal alterations with adolescent HC use on PFC development. To address this gap, we examined molecular and functional markers of cortical maturation in female rats treated with HCs in adolescence. Intact female Sprague-Dawley rats were randomly assigned to receive daily subcutaneous injections of either vehicle or HCs (10 µg ethinyl estradiol + 20 µg levonorgestrel) for the duration of adolescence from postnatal day (PND) 35-56. Blood and brain tissue was collected at PND 57 and behavioral assays completed between PND 57-63. HC treatment was effective, as vaginal lavage indicated disrupted estrous cycling and ELISA quantification showed suppression of serum luteinizing hormone in HC-treated rats. Further, in HC treated rats, liquid chromatography/mass spectrometry detected low serum estradiol levels and HC presence in serum and the brain. Within the medial PFC, gene expression profiling with NanoString nCounter custom panel revealed differentially expressed genes with HC treatment, including genes related to glial function, synaptic plasticity, and immune signaling. mPFC immunolabeling for myelin (MBP) and oligodendrocytes (CC1) was found to be increased in HC-treated rats, while Iba1 (microglia) immunolabeling and cell complexity was reduced. HC treatment diminished risk-assessment behavior in the elevated plus maze and novelty-induced hypophagia paradigm. Overall, we show that use of a widely used pharmaceutical (HCs) during a vulnerable developmental period (adolescence) influences PFC maturation, which may contribute to altered risk-assessment behavior. These data have the potential to enhance user agency by pointing to consequences of adolescent HC use not previously identified. Funding: R21 HD109618 

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