Diet effects on female reproduction in high growth (hg/hg) mice that are deficient in the Socs-2 gene

Abstract

-The detrimental effect of larger body size on reproductive performance has been well documented in mouse models of overgrowth, such as Growth Hormone (GH) transgenics. This study describes the reproductive performance of the High Growth (HG) mouse model of overgrowth. The HG mouse model exhibits overgrowth due to a partially recessive autosomal mutation that increases growth rate and mature body size. The HG phenotype results from the lack of expression of Socs-2, which negatively regulates GH signaling. C57BL/6J (C57) and congenic C57BL/6J-hg/hg (HG) female mice were fed four diets differing in protein and energy content, starting at 8 weeks of age. A complete reproductive cycle from mating to weaning was evaluated. HG mice were 40% larger than C57 and had a higher feed intake throughout the experiment. Significant genotype × diet interactions were detected for growth, body composition and reproductive traits. HG females showed poor reproductive performance compared to controls as demonstrated by their lower fertility during mating, which was not overcome by changes in the diet. No differences were detected in litter size, but HG animals exhibited a longer gestation length and heavier pup weaning weights compared to controls. Reproductive impairment in HG seems to be the consequence of the lack of Socs-2 independent of the effects of increased body size on reproduction. genetics / overgrowth / genotype-nutrition interaction / reproduction

Within-Generation Mutation Variance for Litter Size in Inbred Mice

“…The C57BL/6J strain was developed in the early 20th century from a very small founder population and it is considered a classical inbred strain with an almost homozygous genome (Wade and Daly 2005). As reported in other inbred mouse strains (Falconer 1960), our strain showed substantial phenotypic variation for average litter size across generations, average litter size being similar to the estimates reported by other authors (Kirkpatrick et al 1998;Corva et al 2004). Note that this population was not under selection for litter size.…”

Partial phenotype conversion and differential trait response to conditions of husbandry in mice

“…Those positive correlation between female body mass at mating and litter size were described by Holt et al ( 2004 ). In addition, diets may have effects on reproductive performance including litter size (Ghosh et al 2016 ) and an interaction between diet and genotype has been described in growth selected mice (Corva et al 2004 ). Notably, diets with positive effects on body weight also increased reproductive performance in mice (Hoover-Plow et al 1988 ), suggesting that the increases of body weight and litter size in DUC SPF mice are connected.…”

Skeletal effects of growth hormone and insulin-like growth factor-I therapy

“…GH signaling may also occur through influx of extracellular calcium ions through voltage-dependent L-type calcium channels (Gaur et al, 1996) and increased intracellular diacylglycerol (DAG), leading to protein kinase C (PKC)-mediated activation of MAP kinases, p90rsk, and c-fos induction (Anderson, 1992; Campbell et al, 1992; Smal and De Meyts, 1987). Suppressor of cytokine signaling (SOCS) proteins accomplish further regulation of GH signaling through inhibition of the JAK-STAT pathway, leading to either suppression or augmentation of GH signaling (Corva et al, 2004; Greenhalgh et al, 2002; Krebs and Hilton, 2001; Ram and Waxman, 1999). GH signaling occurs through the interaction of several signaling pathways triggered by GHR activation.…”