Interactions Between Reproductive and Immune Systems During Ontogeny: Roles of GnRH, Sex Steroids, and Immunomediators

Abstract

Reproduction is an essential function of every animal species, and its realization depends on a complex of interrelated neural, endocrine, immune, and behavioral reactions. It is now accepted that the neuroendocrine system (including its reproductive component) and the immune system have a reciprocal regulatory influence development and functioning during preand postnatal ontogeny (Watanobe & Hayakawa, 2003; Zakharova et al., 2005; Carreras et al., 2008; Li et al., 2007; Chapman et al., 2009; Wu et al., 2011). The functions of these systems change during ontogeny. In the perinatal period, they are involved not only in regulatory but also in morphogenetic processes, unlike in the postnatal period. The tight bilateral connection between these systems is of special significance during the early, critical period of ontogeny, when the functions necessary for postnatal life of newborns are being established. The key role in the interaction of the reproductive and immune systems is played by the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) and sex hormones. During the perinatal period, they regulate the growth and differentiation of various fetal tissues, including the lymphoid tissue. In postnatal life, the dynamics of endocrine processes related to reproduction are regulated by the level of GnRH secretion into the hypothalamo-pituitary portal circulation. GnRH regulates secretion of pituitary gonadotropins, which regulate secretion of sex hormones. GnRH is also involved in regulation of sexual behavior, transmission of olfactory signals, and control of humoral and cell-mediated immunity. Sex hormones, in turn, regulate GnRH production in the hypothalamus (and, therefore, secretion of pituitary gonadotropins) and also its production in the thymus and spleen (Azad et al, 1998; Hrabovszky et al., 2000). On the other hand, immune system mediators such as thymic peptides and proinflammatory cytokines have a role in controlling the development and functioning of the reproductive system. Interactions of the reproductive and immune systems during early ontogeny are prerequisite to their normal functioning in adult life. Changes in the normal levels of GnRH and sex steroids in the developing fetus or newborn and their exposure to adverse environmental factors cause disturbances in long-term programming of the regulatory mechanisms of both reproductive and immune systems (Jacobson et al., 2000; Razia et al., 2006; Cameron et al., 2008; Champagne & Curley, 2008). The brain is especially sensitive to perinatal programming by sex steroids, which not only contribute to the patterning of brain