Maternal regulation of offspring development in mammals is an ancient adaptation tied to lactation

Abstract

The developmental origins of health and disease (DOHaD) is a paradigm for understanding metabolic diseases of modern humans. Vulnerability to disease is linked to perturbations in development during critical time periods in fetal and neonatal life. These perturbations are caused by environmental signals, often generated or transduced by the mother. The regulation of mammalian development depends to a large extent on maternal biochemical signals to her offspring. We argue that this adaptation is ancient, and originated with the evolution of lactation. Lactation evolved earlier than live birth and before the extensive placental development of modern eutherian mammals. Milk contains a host of signaling molecules including nutrients, immunoglobulins, growth factors and metabolic hormones. As evidenced by marsupials, lactation originally served to supply the biochemical factors for growth and development for what is essentially a fetus to a weanling transitioning to independent existence. In placental mammals maternal signaling in earliest life is accomplished through the maternal–placental–fetal connection, with more of development shifted to in utero life. However, significant development occurs postpartum, supported by milk. Mothers of all taxa provide biochemical signals to their offspring, but for non-mammalian mothers the time window is short. Developing mammals receive maternal biochemical signals over an extended period. These signals serve to guide normal development, but also can vary in response to environmental conditions. The ancient adaptation of lactation resulted in a lineage (mammals) in which maternal regulation of offspring development evolved to a heightened degree, with the ability to modify development at multiple time points. Modern metabolic diseases may arise due to a mismatch between maternal regulation and eventual circumstances of the offspring, and due to a large proportion of mothers that exceed past evolutionary norms in body fat and pregnancy weight gain such that maternal signals may no longer be within the adaptive range.

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development

“…The influence of prenatal VPA exposure on the developmental programming of the metabolic status of the offspring should not be excluded [43]. Moreover, changes in maternal behavior and/or milk production could indirectly contribute to the poor BW gain in offspring, which remains to be examined in detail [17]. In humans, intrauterine VPA exposure has not been recognized as a treatment with a high risk for small birth weight [44].…”

“…Low birth weight, a surrogate marker of an infant"s general health, was occasionally reported among VPA-exposed newborns [5], while the relationship between maternal weight gain during pregnancy and infant body weight has not been emphasized. This is an important link because, in terms of mammalian developmental biology, the impact of the treatment of maternal general health indirectly influences the development of the offspring [17].…”

Roles of MicroRNA across Prenatal and Postnatal Periods

“…In developing mammals, the vulnerability and immature immune status of the fetus and newborn are compensated by maternal factors that are transferred via the placenta or amniotic fluid, during intrauterine life, and by milk after birth [1]. …”

“…During development, mother-fetal cross-talk begins at implantation, via the maternal–placental–fetal axis [1]. The biological dialogue initiates between the maternal reproductive tissue and the conceptus [2].…”

“…After birth, the mother’s milk continues to provide oral biochemical signaling previously provided to the fetus via amniotic fluid [1]. Milk undoubtedly offers the nutritional requirements for growth and infant development, but it is much more than food, providing protection and long-term programming agents for the infant [11].…”