Date of Defense


Date of Graduation



Biological Sciences

First Advisor

Christopher Pearl

Second Advisor

John Spitsbergen

Third Advisor

Kathryn Docherty


Testosterone production by Leydig cells declines during aging in both men and rodent models. Previous results from our lab demonstrated that daily sperm production also declines in aging rats and alterations in the estrogen environment of the testis contribute to this decline. Importantly, estrogen treatment during aging was able to attenuate the age-associated decline in sperm production. However, the cellular and molecular mechanisms by which estrogen maintains sperm production remain unclear. These experiments were designed to further investigate the effects of estrogen on sperm production in an attempt to further define the cellular mechanisms regulated by estrogen within the testis. This study compared untreated rats at 15 months of age to 18 month old rats that were treated with either vehicle or estradiol-valerate once every third day from 15 to 18 months. The first question addressed was whether the effects of estradiolvalerate were direct or indirect via changes in gonadotropin production. Pituitary concentrations of LH and FSH were quantified, and no significant difference was found between any of the three groups. This suggests that estrogen acts directly at the testis to regulate spermatogenesis. Some reports suggest that Sertoli cell numbers decline with age which would lead to reduced sperm production. Therefore, we next asked if age or treatment with estradiol-valerate affected the number of Sertoli cells. GATA-4 positive Sertoli cells were counted from parallel sections using the physical dissector method to estimate total number of Sertoli cells per testis. While the number of Sertoli cells trended lower in 18 month control animals compared to either 15 month control or 18 month treated animals, these differences were not statistically different. This suggests that spermatogenic efficiency, and not the number of somatic cells to support spermatogenesis, is responsible for differences in sperm production during aging. Our final question asked if the amount of apoptosis within the testis varied by age or treatment. The percentage of seminiferous tubules in which apoptotic cells were observed was similar between all three groups. Collectively, these results suggest that estrogen likely regulates sperm production by affecting germ cell proliferation rates and not germ cell survival.

Access Setting

Honors Thesis-Open Access