Healthy functioning mammal male reproductive system is determined during prenatal development: long-term consequences of maternal immune activation

Abstract

The reproductive axis of male mammals implies a coordinated interaction of its three components: a population of gonadotropin-releasing hormone (GnRH)—producing neurons of the hypothalamus, gonadotropic cells of the adenohypophysis, and most distally located testes that produce male sex hormone (testosterone) and germ cells (spermatozoa). It is generally believed that for the accurate and constant realization of reproductive function, the testes must be isolated from the internal environment of the whole organism with the help of a hematotesticular barrier. The internal immune system of the testes is primarily represented by testicular macrophages. They are located primarily in the peritubular space and provide the physical organization of peritubular myoid cells into niche-like clusters that can form an environment conducive to the differentiation of spermatogonia A1 in sperm cells. The development of this complex system occurs in mammals over a long period and is determined by the timely synchronization of all its parts. Maternal immune activation (MIA) is associated with the powerful production of proinflammatory cytokines in the mother’s body and further in the placenta and fetal region. Many of these cytokines have a pleiotropic effect and act as morphogenetic factors. Thus, cytokines can influence the development of testes even in the prenatal period. The review is focused on the effect of MIA on testicular development during prenatal state and on the holistic nature of the development of the reproductive axis of mammals on the example of laboratory rodents. Laboratory rodents (especially mice) are often used to develop models of the development of certain human systems and are the generally accepted standard for the introduction of these models into medical practice.

Keywords

• mammals
• male reproductive axes
• maternal immune stress