Supplementary data - Maternal from Maternal modulation of paternal effects on offspring development

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 <i>via</i> 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 <i>via</i> germline inheritance, but mothers can serve as a modulating factor in determining the impact of paternal influences on offspring development.

跨代传递环境诱导表型的父系传递现象，已在多种不同性质的暴露条件下被报道，且至少部分由通过精子遗传的表观遗传因子所驱动。然而，此前关于父系生殖系传递的研究，并未探究母体在父系效应传递至子代过程中的作用。我们提出假说：雄性暴露于营养限制环境，会影响雄性配偶质量及后续母体生殖投入，进而影响父系生殖系效应的传递。在本研究中，我们通过小鼠胚胎移植（Embryo Transfer）实验证实：成年限食雄性的精子因子，可影响雌性子代的生长速率、下丘脑基因表达及行为表现。然而，在自然交配条件下，与限食雄性交配的雌性会提升产前及产后抚育行为，而胚胎移植实验中观察到的表型效应则消失或发生逆转。我们进一步证实，母体投入的这类代偿性变化，与雌性对限食雄性的配偶偏好降低，以及母鼠下丘脑内基因表达上调存在关联。综上，雄性的经历可通过生殖系遗传影响子代发育，但母体可作为调节因子，调控父系效应对子代发育的影响程度。