Nutritional adversity, sex and reproduction: 30 years of DOHaD and what have we learned?

Abstract

It is well established that early life environmental signals, including nutrition, set the stage for long-term health and disease risk – effects that span multiple generations. This relationship begins early, in the periconceptional period and extends into embryonic, fetal and early infant phases of life. Now known as the Developmental Origins of Health and Disease (DOHaD), this concept describes the adaptations that a developing organism makes in response to early life cues, resulting in adjustments in homeostatic systems that may prove maladaptive in postnatal life, leading to an increased risk of chronic disease and/or the inheritance of risk factors across generations. Reproductive maturation and function is similarly influenced by early life events. This should not be surprising, since primordial germ cells are established early in life and thus vulnerable to early life adversity. A multitude of ‘modifying’ cues inducing developmental adaptations have been identified that result in changes in reproductive development and impairments in reproductive function. Many types of nutritional challenges including caloric restriction, macronutrient excess and micronutrient insufficiencies have been shown to induce early life adaptations that produce long-term reproductive dysfunction. Many pathways have been suggested to underpin these associations, including epigenetic reprogramming of germ cells. While the mechanisms still remain to be fully investigated, it is clear that a lifecourse approach to understanding lifetime reproductive function is necessary. Furthermore, investigations of the impacts of early life adversity must be extended to include the paternal environment, especially in epidemiological and clinical studies of offspring reproductive function.

Maternal undernutrition during pregnancy and lactation affects testicular morphology, the stages of spermatogenic cycle, and the testicular IGF-I system in adult offspring

“…Early-life undernutrition has been associated with a number of postnatal risk factors with an increased propensity for the development of cardiometabolic disorders including type 2 diabetes, hypertension, and obesity. 1 This developmental programming via an adverse intrauterine environment also negatively impacts on reproductive outcomes via changes in the key cellular signaling pathways related to female reproductive development and function 2 and associated impairments in ovarian follicular growth and development. [3][4][5] In males, restriction of maternal protein or caloric intake results in early onset of puberty, reductions in the secretion of key reproductive hormones (follicle-stimulating hormone, FSH; testosterone), and, in adulthood, altered activities of key steroidogenic enzymes.…”

Molecular and Environmental Mechanisms Regulating Puberty Initiation: An Integrated Approach

“…Based on the concept of the developmental origins of health and disease (DOHaD), it has been suggested that the developing fetus modifies homeostatic system activities in response to early life cues. These stressful events associated with intrauterine growth restriction, result in fetal programming of endocrine axes for a stressful extrauterine life, functional changes that are associated with an increased risk of chronic mental and physical non-communicable diseases (64). The precocity in sexual maturation observed in such children can be explained by the following concept: as fetal growth restriction is associated with increased risk of disease and mortality, the developing subject should become capable of reproduction at an earlier stage than anticipated in order to complete the life cycle (65).…”

30th anniversary for the developmental origins of endocrinology

“…Transgenerational effects from developmental programming have also been identified in the reproductive system via effects on male and female gametes. Patrycja Jazwiec and Deborah Sloboda (Jazwiec & Sloboda 2019) review the developmental programming of reproduction, and specifically, gametogenesis. They discuss a substantial body of literature which demonstrate the effects of early life adversity on reproduction, including both overnutrition and undernutrition.…”