Thesis, COLLÉGIALITÉ

Abstract

Brain sexual differentiation is a process that occurs during a period of sensitivity in development and is influenced by steroid hormones. Sex differences in brain and behavior appear due to the organiza tional and activational effects of steroid hormones. In rodents, estrogens are the primary driver of sexual differentiation: estrogens masculinize and defeminize the rodent brain and behavior. The mi croglia, the brain´s innate immune cell, seems to be involved in sexual differentiation. In rodents, more microglia are in the male preoptic area (POA), an important brain region in male sexual behav ior, during the critical period of hormones. Estrogen treatment of females increased microglial counts to those of males. By inhibiting microglia, the masculinizing actions of estrogens on the rodent brain and behavior can be prevented. In the medial preoptic nucleus of female rats, more microglia active ly engulf newborn cells. Thus, the role of microglia in brain sexual differentiation may be mediated through their phagocytic activity during the period of sensitivity to hormones. The Japanese quail is an interesting animal model to investigate since their sexual differentiation also depends on estro gens. In contrast to rodents, estrogens are responsible for the demasculinization of the brain and behavior in quail during the critical period of hormones. Opposed to what is observed in rodents, female quail exhibit more microglia in the medial preoptic nucleus during the critical period. This sex difference depends on estrogen availability. Interestingly, in quail, females remain sensitive to the demasculinizing effect of estrogens until two to four weeks of postnatal life. Microglia could, there fore, also influence brain development during the postnatal weeks. The present research aimed to understand the role of microglia in brain sexual differentia tion in the quail. The first experiment studied the number of phagocytic microglia on embryonic days 10 (E10) and 12 (E12). To visualize phagocytic microglia, a new method was tested in which eggs were injected with fluorescent liposomes. The brain tissue was then stained with a lectin specific to macrophages to visualize the total number of microglia in the POA. In a second experiment, the sex difference in the number of microglia on E12 and the first day of postnatal life (PN1) was investigat ed, as previous experiments reported a marked sex difference on E12, and we suspected that micro glia might also play a role during the demasculinization process after hatching on PN1. To this end, quail embryos were treated with estradiol on E7 to confirm the results obtained by Delage & Cornil (2020) on E12 with a different microglial marker and to investigate a possible sex difference in the microglial count on the first day after birth. To visualize the total microglia, brain slices were stained with the same lectin as before. No results concerning the phagocytic activity of microglia on E10 and E12 could be analyzed due to technical difficulties. Furthermore, there were no significant sex differences in the number of microglia, neither on E12 nor PN1. These differences were also not hormone dependent.