The placenta serves as the interface between maternal resources and fetal growth. Factors on either side may alter the manner in which this interface regulates exchange. For example, alterations in maternal energy balance have a direct impact on fetal growth through the availability of resources such as oxygen, glucose, and amino acids in the maternal circulation [1
]. Indirectly, placental structural and functional modifications mediate the support of fetal growth by maternal resources [2
]. Fetal demand, shaped by factors such as number of fetuses, may also alter placental regulation of exchange [4
]. The marmoset is a novel model in which to examine these aspects of placental function due to early chorionic fusion that leads to multiple dizygotic fetuses sharing a unified placental mass [6
], a condition underlying hemopoietic chimerism in the callitrichine primates [10
The timing and duration of maternal nutrient restriction during pregnancy is related to a range of outcomes in placental weight and the fetal:placental weight ratio [12
]. This ratio has been described as “placental efficiency” [5
]. By this definition, efficiency is not based on direct measurement of metabolic function, but is inferred through the ability of a unit of placental mass to support fetal growth. A decrease in the fetal:placental weight ratio, i.e. a relatively large placenta, has been shown to be a consequence of maternal nutrient restriction during early pregnancy in pigs [14
], rats [15
], and sheep [18
]. Conversely, placental growth may be reduced and the fetal:placental ratio increased when maternal nutritional restriction occurs after the placenta largely has achieved peak growth velocity, usually by mid- to late gestation in most species [12
]. Because these relatively smaller placentas support higher per unit fetal growth, it has been argued that the response of the placenta to limits on physical growth is to increase metabolic efficiency [12
]. Increases in litter size may reduce the availability of maternal resources per individual fetus in the absence of overt maternal undernutrition.
In the common marmoset monkey, variation in litter size and total fetal mass is associated with differences in intrauterine resource availability between twin and triplet litters [6
]. Triplet marmoset pregnancies are characterized by higher maternal prepregnant weights and pregnant weight gains overall, but maternal mass available per fetus is lower for individual triplets than for individual twins [6
] and mothers of triplets do not increase energy intake during pregnancy [21
]. Rutherford and Tardif [6
] demonstrated that the fetal:placental weight ratio is higher in the marmoset triplet pregnancy, meaning that one gram of triplet placenta produces more fetal mass than does one gram of the twin placenta. Mechanisms supporting this higher fetal:placental weight ratio in marmosets are unknown, but may involve differences in the microscopic structural correlates of function.
The microscopic architecture of the placenta exhibits structural and functional plasticity in the context of intrauterine environmental variation. Maternal undernutrition before and throughout pregnancy in the guinea pig leads to decreased birth weights and increased fetal:placental weight ratio, but labyrinth surface area is reduced and the thickness of the exchange membrane at the maternal-fetal interface is increased [22
]. In baboons, maternal nutrient restriction leads to reductions in villous volume and surface area [23
]. Placentas from human pregnancies complicated by IUGR both with [24
] and without pre-eclampsia [24
] exhibited significant reductions in villous volume and surface area. Less is known about the effects of increased litter size on placental morphological characteristics and attendant function related to nutrient transport, largely because in the litter-bearing animal models commonly referenced (e.g. rats, guinea pigs), each fetus is associated with an individual placenta [25
]. In sheep twin litters, fetuses share a common cotyledonary placenta, and cotyledon number [4
] and absolute cotyledon surface area [27
] increases with litter size, suggesting mechanism by which the placenta adjusts efficiency can be as fetal demands grow.
To clarify the role of litter size variation, and hence variation in total fetal metabolic demand, in the development of placental architecture in the marmoset monkey, this study addresses the following questions: 1) How does the microscopic composition vary according to litter condition (offspring number, total litter mass)?; 2) What is the relation of trabecular surface area to litter size and weight?; and 3) Is the observed variation consistent with an interpretation of increased efficiency of the triplet placenta in support of fetal growth?