Sex differences in developmental programming models

Aiken, Catherine; Ozanne, Susan E.

doi:10.1530/rep-11-0489

Cited by 295 publications

(295 citation statements)

References 135 publications

(158 reference statements)

Supporting

Mentioning

255

Contrasting

Unclassified

Order By: Relevance

“…Although myostatin deficiency affected both sexes, more of the muscle groups were affected in WT male offspring than in female offspring (5), suggesting a more robust phenotype in the males. Sex differences are commonly observed in developmental programming models and often times more drastically affect males than females, although the molecular mechanisms driving the sexual dimorphic nature of developmental programming outcomes remain largely unknown (33).…”

Section: Discussionmentioning

confidence: 99%

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Oestreich

Kamp

McCray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.osteogenesis imperfecta | developmental origins of health and disease | fetal programming | myostatin | bone health O steogenesis imperfecta (OI) is a genetically and clinically heterogeneous heritable connective tissue disorder characterized by anomalies in type I collagen-containing tissues, particularly bone. Clinical manifestations include osteopenia/osteoporosis, fractures, skeletal deformities, short stature, and skeletal muscle weakness. Current therapies entail use of antiresorptive drugs and surgical interventions but have limited success (1). New approaches that decrease fracture risk while minimizing long-term damage to bone integrity are greatly needed. Myostatin, or growth and differentiation factor 8 (GDF8), is a TGF-β family member and negative regulator of muscle growth and development. It is highly conserved across species, primarily expressed in muscle cells, and participates in paracrine and endocrine signaling (2). Recently, we and others have shown that inhibiting myostatin, either genetically or pharmacologically, increases muscle mass and improves bone microarchitecture (3) and mechanical strength (4) in the OI murine (Col1a2 oim ) model. In addition to regulating muscle growth postnatally, myostatin deficiency in the maternal environment increases muscle mass in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Oestreich

Kamp

McCray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Although WD-fed male offspring had a less severe phenotype, they did have substantially increased white fat deposition and some features of dyslipidemia. There are several potential explanations for the gender discrepancies between female and male mouse and human offspring in response to a hypercholanemic intrauterine environment, including the relatively short duration of WD feeding, the adolescent nature of the NFBC 1986 offspring, and species-specific differences (37). However, the metabolic profiles of both males and females exposed to increased BA in utero, in both the mouse model and in humans with ICP, were associated with a preobese and prediabetic phenotype as well as altered morphometric and biochemical profiles.…”

Section: Discussionmentioning

confidence: 99%

Maternal cholestasis during pregnancy programs metabolic disease in offspring

Papacleovoulou¹,

Abu‐Hayyeh²,

et al. 2013

View full text Add to dashboard Cite

The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

show abstract

“…Notably, investigations of sexually dimorphic developmental trajectories, however, overwhelmingly essentialize the role of the mother and sex-biased allocation of maternal resources. More often overlooked are sexually differentiated mechanisms within offspring that influence utilization and assimilation of early life nutrition and environmental signals [26,[95][96]. Consideration of progenyspecific adaptations as well as biased maternal effort will contribute to a better understanding of the ontogeny of sexual dimorphism.…”

Section: Discussionmentioning

confidence: 99%

Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

Hinde

Carpenter

Clay

et al. 2014

Preprint

View full text Add to dashboard Cite

Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sexbiased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ,445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date.

show abstract

Sex differences in developmental programming models

Cited by 295 publications

References 135 publications

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Maternal cholestasis during pregnancy programs metabolic disease in offspring

Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

Contact Info

Product

Resources

About