Maternal weight affects placental DNA methylation of genes involved in metabolic pathways in the common marmoset monkey (Callithrix jacchus)

Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset, Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome-wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including the regulation of glycolytic and lipid metabolic processes pathways.     

Body mass growth in common marmosets: Toward a model of pediatric obesity

While much is known about adult obesity in nonhuman primates, very little is known regarding development of childhood adiposity. As small monkeys that are easy to handle and have a relatively fast life history, common marmoset monkeys (Callithrix jacchus) offer interesting opportunities to examine the question of fat versus lean mass growth in a nonhuman primate. This article provides an overview of our understanding of early life growth in mass in marmoset monkeys, based primarily upon our past 20 years of research, culminating in our recent findings on early life obesity in this species. Common marmosets display variance in early life growth patterns that is related to both pre‐ and postnatal factors and the marmoset uterine environment is exquisitely designed to reflect resources available for the gestation of multiple offspring, making them an interesting model of developmental programming. We have demonstrated that obesity can be generated in very early life in captive marmosets, with excess adiposity evident by one month of age, making this species a potentially valuable model in which to study pediatric obesity and its sequelae. Birth weight is associated with adiposity in animals vulnerable to obesity. Early life exposure to higher fat diets enhances the chances of postweaning obesity development. However, overall higher food consumption is also associated with obesity development at later ages. One unexpected finding in our studies has been the relatively high body fat percentage of neonatal (12–18%) marmosets suggesting that hypotheses regarding the uniqueness of high human neonatal adiposity merit further examination. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Cervical Cytology Specimen Stability in Surepath Preservative and Analytical Sensitivity for HPV Testing with the cobas and Hybrid Capture 2 Tests

None of the commercial HPV tests are U.S. FDA-approved for testing of cervical cytology specimens in SurePath preservative. Still, ~30% of HPV testing is performed on specimens in this formalin-containing preservative. Formalin-induced DNA fragmentation and cross-linking may interfere with HPV detection. We evaluated analytical sensitivity and specimen stability of the cobas 4800 HPV (Roche) and Hybrid Capture 2 HPV (HC2, Qiagen) tests with residual cervical cytology samples in SurePath preservative available within 1 week of collection. Cobas testing was performed with and without heating samples at 120°C for 20 min diluted 1:1 in an alkaline environment (pretreatment) to revert DNA crosslinking. Stability was tested after 2 weeks of storage at ambient temperature followed by ≤10 weeks at 4°C. Analytical sensitivity and positivity rates (HC2, 18%; cobas pretreated, 46%; cobas untreated, 47%) were greater for cobas than HC2 (n = 682). After 6 weeks of storage, mean HC2 ratios were lower (mean 0.9, SD 6.3) but high variability limited statistical power to detect trends. Cobas threshold cycles (Ct’s) increased in untreated (mean 2.1) but not pretreated samples (mean 0.3; n = 110; p≤0.0001). Overall, cobas had greater analytical sensitivity for samples in SurePath preservative. Although pretreatment introduced a manual sample transfer step and 30 min of incubation times, it improved stability without negatively affecting analytical sensitivity. While awaiting results of large trials to evaluate the clinical performance of cobas, the addition of the pretreatment step may improve the detection of HPV, especially after prolonged sample storage.     

Relations among birth condition, maternal condition, and postnatal growth in captive common marmoset monkeys (Callithrix jacchus)

The present study characterizes the relations among maternal condition, litter size, birth condition, and growth in body weight for a population of common marmosets. The subjects of the study were marmosets born into a single colony between 1994 and 2001. Three sets of analyses were conducted to answer the following questions: 1) Is there a relationship between litter size, maternal condition, and birth condition? In the study population, maternal body weight, maternal age, litter size, and birth condition were related in a complex fashion. Birth weight and prenatal long‐bone growth, as reflected in knee–heel length, were both related to maternal age, with older mothers supporting higher prenatal growth. Age and maternal condition appeared to interact as determinants of long‐bone growth, as the combination of older and larger mothers resulted in significantly longer knee–heel lengths in their offspring. 2) Is there a relationship between birth condition or maternal condition and subsequent growth or final adult size? The early growth rate in this population was similar to early growth rates reported for three different marmoset colonies, suggesting that early growth may be relatively inflexible in this species. However, within this population, the variation that did occur in early growth rate was related to birth weight and maternal weight. Later growth and adult weight were related to birth weight and litter size: small twin infants displayed slower later growth rates and were smaller as adults than twins that began life at a higher birth weight, while the birth weight of triplets was not related to adult size. In these marmosets, small infants that were the result of increased litter size differed from small infants whose small birth size resulted from other factors. This reinforces the proposal that the causes of low birth weight will be relevant to the development of the marmoset as a model of prenatal environmental effects. Am. J. Primatol. 62:83–94, 2004. © 2004 Wiley‐Liss, Inc.     

Cellulolysis is severely affected in Clostridium cellulolyticum strain cipCMut1

Progress towards understanding the molecular basis of cellulolysis by Clostridium cellulolyticm was obtained through the study of the first cellulolysis defective mutant strain, namely cipCMut1. In this mutant, a 2 659 bp insertion element, disrupts the cipC gene at the sequence encoding the seventh cohesin of the scaffoldin CipC. cipC is the first gene in a large 'cel' gene cluster, encoding several enzymatic subunits of the cellulosomes, including the processive cellulase Cel48F, which is the major component. Physiological and biochemical studies showed that the mutant strain was affected in cellulosome synthesis and severely impaired in its ability to degrade crystalline cellulose. It produced small amounts of a truncated CipC protein (P120), which had functional cohesin domains and assembled complexes which did not contain any of the enzymes encoded by genes of the 'cel' cluster. The mutant cellulolytic system was mainly composed of three proteins designated P98, P105 and P125. Their N-termini did not match any of the known cellulase sequences from C. cellulolyticum. A large amount of entire CipC produced in the cipCMut1 strain by trans-complementation with plasmid pSOScipC did not restore the cellulolytic phenotype, in spite of the assembly of a larger amount of complexes. The complexes produced in the mutant and complemented strains contained at least 12 different dockerin-containing proteins encoded by genes located outside of the 'cel' cluster. The disturbances observed in the mutant and trans-complemented strains were the result of a strong polar effect resulting from the cipC gene disruption. In conclusion, this study provided genetic evidence that the cellulases encoded by the genes located in the 'cel' cluster are essential for the building of cellulosomes efficient in crystalline cellulose degradation.     

Use of antisense RNA to modify the composition of cellulosomes produced by Clostridium cellulolyticum

The enzymatic composition of the cellulosomes produced by Clostridium cellulolyticum was modified by inhibiting the synthesis of Cel48F that is the major cellulase of the cellulosomes. The strain ATCC 35319 (pSOSasrF) was developed to over-produce a 469 nucleotide-long antisense-RNA (asRNA) directed against the ribosome-binding site region and the beginning of the coding region of the cel48F mRNAs. The cellulolytic system secreted by the asRNA-producing strain showed a markedly lower amount of Cel48F, compared to the control strain transformed with the empty plasmid (pSOSzero). This was correlated with a 30% decrease of the specific activity of the cellulolytic system on Avicel cellulose, indicating that Cel48F plays an important role in the recalcitrant cellulose degradation. However, only minor effects were observed on the growth parameters on cellulose. In both transformant strains, cellulosome production was found to be reduced and two unknown proteins (P105 and P98) appeared as major components of their cellulolytic systems. These proteins did not contain any dockerin domain and were shown to be not included into the cellulosomes; they are expected to participate to the non-cellulosomal cellulolytic system of C. cellulolyticum.     

Reproduction in captive common marmosets (Callithrix jacchus)

Though sexual maturation may begin at around one year of age, first successful reproduction of the common marmoset (Callithrix jacchus) is likely to be later, and it is generally recommended that animals not be mated before 1.5 years of age. The average gestation period is estimated to be 143 to 144 days. A crown-rump length measurement taken by use of ultrasonography during the linear, rapid, prenatal growth phase (between approx. days 60 and 95) can be compared against standard growth curves to estimate delivery date to within 3 to 4 days, on average. Marmosets produce more young per delivery than does any other anthropoid primate, and have more variation in litter size. Many long-established colonies report that triplets are the most common litter size, and there is documented association between higher maternal body weight and higher ovulation numbers. Higher litter sizes generally do not generate higher numbers of viable young. Marmosets are unusual among primates in having a postpartum ovulation that typically results in conception and successful delivery; reported median inter-birth intervals range from 154 to 162 days. However, pregnancy losses are quite common; one study of a large breeding colony indicated 50 percent loss between conception and term delivery. The average life span for breeding females is around six years; the range of reported average lifetime number of litters for a breeding pair is 3.45 to 4.0. Our purpose is to provide an overview of reproduction in the common marmoset, including basic reproductive life history, lactation and weaning, social housing requirements, and common problems encountered in the captive breeding of this species. A brief comparison between marmoset and tamarin reproduction also will be provided.