Intergenerational transmission of maternal care deficiency and offspring development delay induced by perinatal protein malnutrition

Abstract

Objectives: Early life represents a sensitive and critical period for an individual. Nutrition plays a crucial role in the maturation and functional development of the central nervous system. Inadequate nutrition before birth and during the postnatal life can seriously interfere with brain development and lead to behavioral and neurological disorders such as learning disabilities and psychiatric diseases. In addition, the quality of mother–infant interactions represents an important adaptive pathway that prepares offspring for the conditions of life. In this work, we asked if protein malnutrition alters maternal care and offspring development and if these phenotypes can be transmitted to next generation.

Methods: Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. Nurturing behaviors, i.e. arched, blanket and passive nursing, and liking and grooming of the pups, were evaluated from postnatal day 1 (PD1) to postnatal day 7 (PD7). The same protocol was employed to evaluate maternal behavior for filial generation 1 (F1) and filial generation 2 (F2) dams. Offspring development was evaluated for F1, F2, and F3 generations. Developmental landmarks and neurological reflexes were assessed from PD8 until complete development of the landmark or acquisition of the reflex.

Results: Our results show that malnourished dams provide a lesser and more fragmented maternal care than their normally fed counterparts. This altered maternal behavior as well as the delay in the physical and neurological development observed in the offspring from malnourished mothers was transmitted up to two generations at least.

Conclusion: These results highlight the harmful effects of protein malnutrition even for generations that are not directly exposed to this environmental adversity.

KEYWORDS:

• Early-life stress
• Environmental adversity
• Intergenerational transmission
• Maternal behavior
• Neurodevelopment
• Nurturing

ORCID

Octavio Gianatiempo http://orcid.org/0000-0001-5660-942X

Eduardo T. Cánepa http://orcid.org/0000-0002-4322-1650