Maternal modulation of paternal effects on offspring development

Abstract

The paternal transmission of environmentally induced phenotypes across generations has been reported to occur following a number of qualitatively different exposures and appear to be driven, at least in part, by epigenetic factors that are inherited via the sperm. However, previous studies of paternal germline transmission have not addressed the role of mothers in the propagation of paternal effects to offspring. We hypothesized that paternal exposure to nutritional restriction would impact male mate quality and subsequent maternal reproductive investment with consequences for the transmission of paternal germline effects. In the current report, using embryo transfer in mice, we demonstrate that sperm factors in adult food restricted males can influence growth rate, hypothalamic gene expression and behaviour in female offspring. However, under natural mating conditions females mated with food restricted males show increased pre- and postnatal care, and phenotypic outcomes observed during embryo transfer conditions are absent or reversed. We demonstrate that these compensatory changes in maternal investment are associated with a reduced mate preference for food restricted males and elevated gene expression within the maternal hypothalamus. Therefore, paternal experience can influence offspring development via germline inheritance, but mothers can serve as a modulating factor in determining the impact of paternal influences on offspring development.

Interplay between paternal germline and maternal effects in shaping development: The overlooked importance of behavioural ecology

“…The next step in building a paternal germline transmission hypothesis is to establish that the sperm from exposed males and the epigenetic variation in those sperm are capable of inducing phenotypic changes in the progeny of those males. In vitro fertilization and embryo transfer studies indicate that the sperm (and associated seminal fluids) of males exposed to social stress (Dietz et al, ), fear conditioning (Dias & Ressler, ) and chronic food restriction (Mashoodh, Habrylo, Gudsnuk, Pelle, & Champagne, ) is predictive of developmental outcomes in offspring. Foundational studies of the transmission of epimutations in mice illustrate the role of sperm RNAs in this transmission (Rassoulzadegan et al, ).…”

“…Mate preference tasks indicate that F3 male rats from vinclozolin‐exposed lineages are less preferred as mates (Crews et al, ) as are male mice exposed in utero to food restriction (Meikle, Kruper, & Browning, ) and male rats exposed to either high‐fat diet (Korgan, O'Leary, King, Weaver, & Perrot, ) or predator odours (Korgan et al, ). When female mice are presented with urine from food‐restricted or control‐fed male mice, they exhibit preference for the control‐fed males (Mashoodh et al, ). In these examples, females can clearly distinguish between males, dependent on the environmental exposure history of the male.…”

“…Female rats rearing offspring from predator odour‐exposed males engage in elevated licking/grooming and arched back nursing compared with females rearing offspring of non‐exposed males—though this effect is only observed when females are rearing pups in a semi‐naturalistic environment (Korgan et al, ). Increased post‐natal maternal care is also observed when female mice are mated with males that have experienced social enrichment (compared with isolation‐reared males) or males that have been exposed to food restriction in adulthood (Mashoodh, Franks, Curley, & Champagne, ; Mashoodh et al, ). Though it is challenging to determine the level of prenatal maternal investment in mammals, female mice mated with food‐restricted males gain more weight during pregnancy, suggestive of increased gestational food intake (Mashoodh et al, ).…”

“…Increased post‐natal maternal care is also observed when female mice are mated with males that have experienced social enrichment (compared with isolation‐reared males) or males that have been exposed to food restriction in adulthood (Mashoodh, Franks, Curley, & Champagne, ; Mashoodh et al, ). Though it is challenging to determine the level of prenatal maternal investment in mammals, female mice mated with food‐restricted males gain more weight during pregnancy, suggestive of increased gestational food intake (Mashoodh et al, ). Thus, the impact of paternal exposures that are known to influence offspring outcomes can also be observed at the level of maternal investment by female mates and these reproductive adjustments illustrate both DA and RC.…”

“…Paternal obesity in mice is associated with altered expression of imprinted genes in the placenta, including Peg3 , Peg9 , Peg10 and the Slc38a2 gene that encodes for a sodium‐coupled neutral amino acid transporter (Mitchell et al, ). Female mice mated with a food‐restricted male have increased hypothalamic expression of Peg3 and other genes involved in post‐natal maternal care which may facilitate the paternal effects on maternal post‐natal reproductive investment (Mashoodh et al, ).…”