The foetal programming effects of a mild gestational food restriction protocol in mice: are the results comparable with those of intragestational ghrelin administration?.

TORRES PJ; LUQUE EM; FUX-OTTA C; DI GIORGIO, NOELIA PAULA; PONZIO M.F; CANTARELLI VI; LUX-LANTOS, VICTORIA; MARTINI A.C.

Congreso; International Congress of Endocrinology 2021; 2021

Introduction: Severe food restriction during pregnancy and/or lactation (50% food restriction or more) induces fetal programming. It is not clear nevertheless, if these effects are the consequence of maternal increased levels of ghrelin (Ghrl), a food scarcity signal. Furthermore, it has not been investigated if mild food restriction is also able to exert fetal programming.Objectives: The objectives of this study were to explore 1) if a 15% food restriction protocol during pregnancy in mice, programs the postnatal development of the offspring, with emphasis on reproductive function, and 2) to assess if the administration of Ghrl to mice dams, exerts effects that mimic those obtained by mild caloric restriction.Methods: Adult female mice were 15% food restricted or injected with 4 nmol/animal/day of Ghrl during pregnancy. Control animals were injected with the vehicle. After birth, pups did not receive further treatment. Parameters evaluated in pups were birth weight, body weight evolution, physical and neurobiological maturation, puberty onset and reproductive function at adulthood.Results: Pups from food restricted dams were thinner at birth (vs Ghrl) but catched up. Pups from Ghrl dams were heavier at birth and gained more weight. This effect was not associated with differences in plasma IGF-1 levels. Dams food restriction delayed the physical maturation of the offspring (pinna detachment and eyes opening), while Ghrl advanced it. Intragestational food restricted pups showed also an impaired response to the surface righting reflex. Dams food restriction and Ghrl administration advances vaginal opening in the offspring and, at adulthood, pups from foodrestricted mice showed a significant decrease in viable litter size, plasma progesterone and an increase in the percentageof females with embryo loss. Ghrelin male pups delayed testis descent. Changes in puberty onset were not associatedwith Kiss1 expression in hypothalamic nuclei (arcuate and anteroventral periventricular). At adulthood, male pups from food restricted dams showed a decrease in epididymal sperm motility and viability.Conclusion: In mice, a mild food restriction protocol during gestation exerts long lasting effects on physical, neurobiological and sexual maturation of the offspring, affecting also reproductive function at adulthood. These effects are not comparable with those of intragestational Ghrl administration.