In birds, exposure to exogenous testosterone during embryonic development can suppress measures of immune function; however, it is unclear whether these effects are due to direct or indirect action via aromatization. Estradiol (E2) 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 E2 can affect immune function. We tested the hypothesis that some of the immunomodulatory effects observed in response to in ovo testosterone exposure in birds are mediated by conversion to E2 by aromatase, by using fadrozole to inhibit aromatization of endogenous testosterone during a crucial period of embryonic immune system development in domestic chickens (Gallus gallus). 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. Because testosterone has a reputation for immunosuppression, we predicted that if modulation of an immune measure by testosterone is dependent on aromatization, then inhibition of estrogen production by fadrozole treatment would lead to elevated measures of that parameter. Conversely, if testosterone inhibits an immune measure directly, then fadrozole treatment would likely not alter that parameter. Fadrozole treatment reduced circulating E2 in female embryos, but had no effect on males or on testosterone in either sex. Fadrozole-treated chicks had decreased day 3 plasma IgY antibody titers and 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 post-hatch. The alteration of several indicators of immune function in fadrozole-treated chicks implicates aromatization as a relevant pathway through which developmental exposure to testosterone can affect immunity in birds
General and Comparative Endocrinology
Simkins, Jeff W.; Joseph, Abby E.; Bonier, Frances; and Benowitz-Fredericks, Z. Morgan. "Prenatal aromatase inhibition alters postnatal immunity in domestic chickens (Gallus gallus)." (2020) .