Simkins, Bonier, and Benowitz-Fredericks Master Data.xlsx

In birds, exposure to testosterone during embryonic development can suppress immune function; however, it is unclear whether this is caused by direct stimulation of androgen receptors. Estradiol is synthesized from testosterone by the enzyme aromatase, and this conversion is a necessary step in many signaling pathways that are ostensibly testosterone-dependent. Many lines of evidence in mammals indicate that estradiol can affect immune function. We tested the hypothesis that immunosuppressive effects of avian <i>in ovo</i> testosterone exposure are mediated by conversion to estradiol by aromatase, using Fadrozole to inhibit aromatization of endogenous testosterone during a crucial period of embryonic immune system development in domestic chickens (<i>Gallus gallus</i>). We then measured total IgY antibody count, response to PHA challenge, mass of thymus and bursa of Fabricius, and plasma testosterone post-hatch on days 3 and 18. We predicted that if immunomodulation by testosterone is dependent on aromatization, then Fadrozole treatment would lead to elevated immune activity by inhibiting estrogen production. Conversely, if testosterone inhibits immune function directly by binding to androgen receptors, then Fadrozole treatment would likely not alter immune function. Fadrozole treated birds had decreased day 3 plasma IgY antibody titers but there was a strong trend towards increased day 18 thymic mass. Furthermore, Fadrozole treatment generated a positive relationship between testosterone and thymic mass in males, and tended to increase day 18 IgY levels for a given bursal mass in females. There was no effect on PHA response, bursal mass, or plasma testosterone at either age. Overall, Fadrozole treated birds tended to have elevated indicators of immune function, implicating aromatization as a relevant pathway through which developmental exposure to testosterone can affect immunity.