Effects of paternal overnutrition and interventions on future generations

Abstract

In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.

Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area

“…Moreover, the present study has focused specifically on maternal diet. However, evidence suggests that paternal overnutrition can also influence offspring health [ [64] , [65] , [66] ] even though maternal obesity may be a stronger predictor of offspring body mass index [ 67 ]. Much evidence also indicates that developmental programming is highly dependent on the sex of the offspring [ 68 ].…”

Effects of parental overweight and obesity on offspring’s mental health: A meta-analysis of observational studies

“…The mechanisms explaining how the father may affect the neurodevelopment of offspring are still under debate [ 70 ].Obesity causes a variety of symptoms in men, including changes in their gut microbiome, hormone levels, and sperm health, which can lead to abnormalities in fertilization and embryonic development [ 71 – 73 ]. Additionally, seminal plasma has a distinct microbiome that can be altered by a high-fat diet(HFD), which means it can indirectly affect the offspring’s neurodevelopment and later brain function by passing along information about the father’s eating habits and metabolic condition [ 74 ].…”

“…Furthermore, sncRNAs have been hypothesized as another pathway of epigenetic transfer, particularly through the paternal line. These sperm-derived RNAs appear to be sensitive to a diverse range of psychological and physiological conditions, including stress exposure and nutrition, and are able to transmit intergenerational information through the paternal lineage [ 70 , 72 , 73 ]. Obesity-caused hyperglycemia, insulin resistance, and a proinflammatory lipotoxic environment could be the immediate source of such epigenetic changes, resulting in developmental brain problems in offspring [ 3 ].…”

“…fertilization and embryonic development [71][72][73]. Additionally, seminal plasma has a distinct microbiome that can be altered by a high-fat diet(HFD), which means it can indirectly affect the offspring's neurodevelopment and later brain function by passing along information about the father's eating habits and metabolic condition [74].…”

Early Life Nutrition and the Development of Offspring Metabolic Health

“…The developmental origins of health and disease (DOHaD) hypothesis describes the effects of parental perturbations around the periconception, pregnancy, and perinatal window that may lead to changes in offspring development and an increased risk of disease [ 1 ]. DOHaD, or simply “developmental programming”, refers to alterations in the physiology, metabolism, and epigenome of an offspring due to poor influences from the offspring’s father or mother [ 2 ]. It is well-established that the maternal in utero and early life (perinatal) environments are key to normal organ development and, thus, the disease risk in her offspring [ 3 ].…”