Undergraduate Honors Theses

Thesis Defended

Spring 2019

Document Type


Type of Thesis

Departmental Honors


Integrative Physiology

First Advisor

Pei-San Tsai


Gonadotropin-releasing hormone (GnRH) is an indispensable hormone for the commencement and maintenance of vertebrate reproduction. The development of GnRH neurons depends greatly on fibroblast growth factor (FGF) signaling. Inactivating mutations on FGF receptor 1 (FGFR1) have been shown to reduce GnRH, leading to compromised fertility in humans. However, how FGFR1 deficiency impacts the structural integrity of the GnRH neuronal network, gonadal function, and growth of the reproductive tract in adults was not well understood. This study investigates the organization of GnRH neurons, ovarian structures, and uterine mass in adult female mice globally deficient in FGFR1 (FGFR1-floxed mice). We hypothesized that there would be decreased GnRH neuron numbers associated with altered ovarian structure and uterine growth in FGFR1-deficient mice. This investigation was accomplished by quantifying (1) GnRH neurons in different brain regions, (2) ovarian follicles and corpora lutea, and (3) mass of the uterus, an estrogen- and progesterone-dependent organ. Our results confirmed that there was a 66% reduction in the number of GnRH neurons in FGFR1-floxed mice. Specifically, this reduction occurs uniformly in all brain regions where GnRH neurons reside. This reduction in GnRH neurons was coupled with decreased numbers of maturing or mature ovarian follicles. Surprisingly, the uterine mass of the FGFR1-floxed mice was increased by about 40% due to unknown causes. These results suggest FGFR1 deficiency negatively impacts GnRH neurons in all brain regions and significantly alters the ovarian and uterine function in females. This study highlights how a single deletion of a signaling gene can lead to downstream defects that cause infertility and other reproductive disorders.