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Reallocation of body resources in lactating mice highly selected for litter size¹

W. M. Rauw^2,*, P. W. Knap, L. Gomez-Raya^*, L. Varona^* and J. L. Noguera^*

^* Àrea de Producció Animal, Centre UdL-IRTA, 177, 25198 Lleida, Spain and and PIC International Group, D-24826 Schleswig, Germany

² Correspondence:
phone: +34 973 70 26 30; fax: +34 973 23 83 01; E-mail:
wendy.rauw{at}irta.es.

	Abstract

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The present study investigated differences in the allocation patterns of body stores in lactating female mice from a line selected for high litter size at birth (S-line, average litter size of 20) and dams from a nonselected control line (C-line, average litter size of 10). Body weight, litter size, litter weight, and absolute and relative lipid and protein mass were measured at peak lactation (2 wk in lactation) and at weaning (3 wk in lactation). Body size in S-line females has been increased as a correlated effect of selection for high litter size at birth, allowing for larger litters and higher absolute milk production. However, these dams produce larger litters relative to their own body weight. At peak lactation, lipid and protein percentage did not differ between lines. At weaning, S-line females had a higher protein percentage (P < 0.001) and lower lipid percentage (P < 0.05) than C-line females. Apparently, S-line females produce more offspring but at a greater cost to their own metabolism. This process was insufficient to supply the offspring with adequate resources, resulting in reduced (P < 0.0001) pup development and increased (P < 0.0001) preweaning mortality rates.

Key Words: Body Composition • Lactation • Mice • Resource Allocation • Selection

	Introduction

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During the first half of pregnancy, body protein and lipid content is increased for later support of fetal growth and lactation (Luz and Griggio, 1996). Lactation has been noted to be the period of peak energy demand (Oftedal, 1984). Rauw et al. (2002) showed that female mice that originate from a line selected for high litter size at birth (S-line, average litter size of 20 pups) have a significantly lower residual food intake (RFI) from parturition to peak lactation (0 to 2 wk in lactation) and from peak lactation to weaning (2 to 3 wk in lactation) than dams from a nonselected control line (C-line, average litter size of 10 pups). Residual food intake is an estimate of the total amount of resources available to an animal for processes other than maintenance and (re)production and is therefore suggested to be an estimate of the total amount of resources that are left for other functions, such as physical activity and the ability to cope with unexpected stress (Rauw et al., 2000a). Therefore, the results of the study suggest that lactating dams selected for high litter size allocate relatively more resources to maintenance of offspring than nonselected dams.

The aforementioned study investigated food resource allocation patterns during lactation. The main objective of the present study is to investigate differences in the allocation patterns of body stores, as quantified by absolute and relative lipid and protein mass in S- and C-line dams at the lactation peak and at weaning.

Furthermore, since tissues with high protein or high lipid levels have different maintenance requirements, line differences in body composition may explain part of the variation in RFI in lactating C- and S-line dams (Luiting, 1990). Therefore, the second objective of this study was to investigate if observed differences between lactating C- and S-line dams in body composition are consistent with expectations from previously documented differences between the lines in RFI.

	Materials and Methods

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Animals
Two lines originating from the 101st generation of the Norwegian mouse selection experiment (e.g., Vangen, 1993) were used: a line selected for high litter size at birth (S-line) and a nonselected control line (C-line). The dams used in the present study themselves originated from litters that were standardized at birth: litters that were larger than eight pups were cut down to eight pups per litter. Average litter size at birth in the 101st generation was 10 in the C-line and 21 in the S-line.

Eighty S-line females and 79 C-line females were randomly mated on the same day at 7.5 to 9 wk of age, with the restriction of no matings between sibs, half-sibs, or cousins (according to the Norwegian mouse selection experiment). After parturition, the litters were not standardized. At parturition 56 females per line were randomly selected and either allocated to a group that was killed at peak lactation (2 wk in lactation; 28 females per line), or a group that was killed at weaning (3 wk in lactation; 28 females per line). Data on lactating females were compared with data on nonreproductive females at 65 d of age (30 females per line), as published earlier by Rauw et al. (2001). Measurements at different physiological stages were made on different animals.

In the period between weaning (at 3 wk of age) and mating of the dams and sires that were used in the present experiment, the animals were housed in pairs with mice of the same sex and the same line. During mating, males were left with the females for 1 wk and were then removed. The mice were housed in 30 cm x 12.5 cm x 12.5 cm cages bedded with sawdust. Animals had free access to pellet concentrate (Kraftför R3, Lactamin AB, Stockholm, Sweden) and water. The food contained 12.6 kJ of ME/g and 21% crude protein, according to the supplier. The light was left on throughout the day (24 h).

Dam body weight (DBW), litter weight (LW), and litter size (LS) were measured at parturition, at peak lactation (2 wk in lactation), and at weaning (3 wk in lactation). At peak lactation and at weaning, DBW, LW, and LS as a percentage of the values at parturition (DBW%, LW%, and LS%, respectively) were calculated. Litter size at parturition included stillborn pups.

Body Composition
Body composition was measured individually at peak lactation and at weaning. Animals were denied access to food 10 h before killing but had free access to water; animals were killed with CO₂ according to accepted procedures. The mice were weighed before and after this procedure. Dead animals were stored at -20°C. Samples were prepared by boiling carcasses individually in closed glass jars that were put in boiling water for 10 min. Subsequently, carcasses were minced individually in a kitchen blender (Group Moulinex, Paris la Défense Cedex, France). Minced samples were stored at -20°C. Total N was estimated by the Kjeldahl method; total protein content was calculated as N x 6.25. Total lipid was estimated by ether extraction pretreated with HCl.

The absolute protein mass was calculated as the protein content in a 1-g sample multiplied by the BW of the dead mouse; absolute lipid mass was calculated in a similar manner. Percentage of protein was calculated by expressing the absolute protein mass as a percentage of the BW of the live mouse; lipid percentage was calculated in a similar way.

Data Analysis
The SAS program (SAS Inst., Inc., Cary, NC) was used for statistical analyses of all traits. The model that was used for analyzing the data was:

(1)

where µ is the overall mean, L_i is the effect of line i (control, selected), PS_j is the effect of physiological stage j (adult, parturition, peak lactation, weaning), (L * PS)_ij is the effect of line i by physiological stage j, e_ijk is the error term of animal k; e_ijk ~ NID(0, ²_e). All traits tested with this model are denoted by Y_ijk measured on animal k of line i and physiological stage j: DBW, LW, LS, DBW%, LW%, LS%, absolute lipid mass, absolute protein mass, lipid percentage, and protein percentage.

Initially, "age" was included as a covariate in the model. Because the effect of "age" was not significant for any of the comparisons, it was excluded from the analysis.

	Results

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Average dam weight at parturition was 37.0 g in the C-line and 53.2 g in the S-line (± 0.44 g; P < 0.0001). This was higher (35 and 37%, respectively) than live BW of the group of virgin females originating from the same generation at 65 d of age (P < 0.0001). Litter size at parturition was 10.6 (± 0.28) in the C-line and 21.4 (± 0.54) in the S-line (P < 0.0001); percentage stillborn was 1.67 (± 0.59) and 1.83 (0.52), respectively (P = 0.84).

The average live DBW, LW, LS, DBW%, LW%, and LS% at peak lactation and at weaning in the C- and S-line are given in Table 1. Females of the S-line had higher DBW than C-line females both at peak lactation and at weaning. However, DBW% at peak lactation and at weaning was very similar in both lines. Litters of the S-line were heavier than C-line litters both at peak lactation and at weaning. However, C-line litters increased more in weight relative to litter birth weight than S-line litters. Litter size, but also mortality rate, was higher in the S-line than in the C-line. Mortality rate in the S-line appeared to be higher from parturition to peak lactation than from parturition to weaning, but the results were not based on the same animals.

Table 3 presents phenotypic correlations, adjusted for the effect of line, physiological stage and line by physiological stage, between absolute lipid mass, absolute protein mass, lipid percentage, protein percentage, and DBW, LW, and LS. Heavier females had a higher absolute lipid and protein mass and a lower protein percentage. Females with heavier litters had a higher absolute protein mass. Females with larger litters had a lower absolute lipid mass, a higher absolute protein mass, and a lower lipid percentage. Females with a higher absolute lipid mass had a higher absolute protein mass.

	Discussion

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Rauw et al. (2001) showed that, at 65 d of age, BW of S-line females was 41% higher than that of C-line females. At parturition, BW in the C- and S-lines was about 35% higher than at 65 d of age. In spite of the larger size and weight of S-line litters, BW from parturition to peak lactation (DBW%) also increased to a similar proportion in the C- and the S-lines and arrived at a similar and lower proportion from parturition to weaning. Several studies reported that selection for high litter size might result in higher mature BW as a correlated effect (e.g., De la Fuente and San Primitivo, 1985; Narayan and Rawat, 1986). This suggests that S-line dams have a larger body size as a correlated response to selection for litter size in order to produce and support their larger litters during gestation and lactation. This hypothesis is supported by the results of Bandy and Eisen (1984). They observed that females selected for high LS and low BW had greater litters but a lower lactational performance than the control line. The question is, does body size in the S-line increase in proportion to the increase in LS, allowing the production of litters of a size that are similarly proportional to their body size, and allowing them to support their litter to a similar extent as C-line females?

Calculation of maternal capacity, which is the total litter weight at birth (in kg) divided by maternal virgin weight (A, in kg) to the 0.83th power (Taylor and Murray, 1987a,b), can be used to test whether S-line dams produce litters to a similar proportion of their body weight as C-line dams. When the average mature asymptotic virgin body weight in the C- and the S-lines is assumed to be 0.0300 and 0.0409 kg, respectively (which is the average of the estimates in these lines by Rauw et al., 2000b; 2002), then the maternal capacity is 0.315 in the C-line and 0.513 in the S-line (P < 0.0001). This indicates that selection for high LS at birth has increased the maternal capacity in the S-line as a correlated effect: S-line females produce larger litters relative to their body size than C-line females.

At parturition, peak lactation, and at weaning, S-line dams were about 45% heavier than C-line dams. This is considerably higher than that found by Eisen and Durant (1980), who observed a BW that was approximately 20% higher at parturition and at 12 d in lactation in female mice selected for high litter size compared to a control line. In that study, selected females originated from the 17th generation of selection and the average was taken of females with standardized LS of 8, 12, and 16 pups, which may account for the difference found between the studies. Several studies have established that daily milk yield is proportional to mature virgin BW to the 0.73th power (Taylor, 1973; Taylor and Murray, 1987a). Body weight was positively and highly correlated with absolute protein mass, which suggests that heavier lactating dams have a higher absolute milk production. This indicates that S-line females produce more milk than do C-line females (absolute protein mass is significantly higher) because of their larger body size.

Whereas the relationship between lipid percentage and protein percentage was strong and negative for virgin females (r = -0.75 when adjusted for line; Rauw et al., 2001), the correlation in lactating females is low and nonsignificant. In virgin animals, an increase in lipid percentage results in a decrease in protein percentage when ash and water mass remain constant: relatively fatter animals are less lean. An explanation for the observation that this was not the case in lactating animals may be that a rising protein content of the milk is accompanied by increasing fat levels (Oftedal, 1984). Indeed, the positive phenotypic correlation between absolute protein and lipid mass shows that an increase in absolute protein mass was accompanied by an increase in absolute lipid mass. Animals with relatively higher milk production will have higher protein, fat, and water contents, and a relatively lower ash content.

In both lines, although significant in the S-line only, the absolute protein mass was lower at weaning than at peak lactation. This can be explained by the fact that pups start to eat solid food after peak lactation allowing for a reduction in dam milk production (Rauw et al., 2002). In both lines, absolute lipid mass was 57% lower in females at peak lactation than in virgin females, suggesting that the degree to which body stores were mobilized was similar in both lines. Absolute lipid mass was lower at weaning than at peak lactation in the S-line and higher at weaning than at peak lactation in the C-line. Although these differences were not significant (P = 0.06 in the C-line and P = 0.70 in the S-line), the results suggest that C-line females regained body condition after peak lactation.

Dams of the C-line managed to increase the LW about four times up to peak lactation, whereas S-line dams increased their LW only three times. Average pup weight (LW divided by LS) at peak lactation was very similar in the C- and S-lines (about 7.4 g), but because of the larger body size of the S-line, the degree of maturity (BW as a percentage of mature virgin BW) was lower in S-line pups than in C-line pups. An increase in LS must be compensated for by a decrease in individual birth weight in order for the maternal capacity to remain at a constant level. The expected degree of maturity is calculated by maternal capacity divided by the product of LS (in kg) and A^0.17 (Taylor and Murray, 1987a, b). Because A equals 0.0300 and 0.0409 kg in the C- and the S-lines, respectively, the degree of maturity is estimated to be 5.41% in the C-line and 4.20% in the S-line (P < 0.0001). This is in very close agreement with earlier observations by Rauw et al. (2002): 5.67% in the C-line and 4.27% in the S-line (P < 0.0001). Pups of the S-line in the study of Rauw et al. (2002) were about 35% less mature than C-line pups up to weaning. Animals with a lower degree of maturity have a lower fitness: preweaning mortality rate was considerably higher in the S-line than in the C-line.

Summarized, S-line females compared to C-line females produced larger litters relative to their own body weight, as indicated by the higher maternal capacity. The results suggest that they produced more milk because of their larger body size and that they had a worse body condition at weaning. Their pups were less mature at birth and remained less mature up to weaning. Therefore, preweaning mortality rate was considerably higher.

Rauw et al. (2002) showed that S-line females had a significantly lower RFI from parturition to peak lactation and from peak lactation to weaning than C-line dams; after weaning, RFI was higher in the S-line than in the C-line. When RFI is not adjusted for body composition, as was the case in the study of Rauw et al. (2002), part of the observed differences between individuals in RFI may be attributable to differing proportions of protein and lipid in the body (Luiting, 1990). Maintenance of body fat requires little energy because it is metabolically relatively inactive, whereas body protein is continually degraded into amino acids and resynthesized. Estimated energy costs of fat and protein turnover are 2 to 3% (Katz and Rognstad, 1976) and 15 to 25% (Mac Rae and Lobley, 1986) of basal energy expenditure, respectively. Therefore, animals with a relatively high lipid content will have lower RFI than animals with relatively high protein content.

Differences in body composition may influence RFI during lactation when, for example, the extent to which body reserves are mobilized and/or the milk composition differ between the lines. Rogowitz and McClure (1995) observed that the milk produced by lactating cotton rats (Sigmodon hispidus) with large litters was dilute and had a lower energy content per dry mass than did the milk produced by animals supporting small litters. Body tissue mobilization, milk yield, and milk composition were not measured in the present study. However, the results show that both lipid and protein percentage were similar in C- and S-line females at peak lactation. At weaning, lipid percentage was lower and protein percentage higher in the C-line than in the S-line, but this cannot explain the observation that RFI after weaning was higher in the S-line.

In conclusion, body size in S-line females increased as a correlated effect of selection for high litter size at birth, allowing for larger litters and higher milk production. However, BW in the S-line did not increase proportionally to the increase in litter size, which is shown by the higher maternal capacity: S-line dams produced larger litters relative to their own BW. This may explain the observation by Rauw et al. (2002) that lactating S-line females had a lower residual food intake, which suggests that they use a relatively larger part of their food intake to support their litter than C-line females. Although this has not been measured directly, the results of the present study do not indicate that, up to peak lactation, S-line females mobilized relatively more body stores than C-line females or that they had a relatively higher milk production. It seems that C-line females had a better body condition after peak lactation than S-line females. Therefore, S-line females produced more offspring but at a greater cost to their own metabolism. This process was insufficient to supply offspring with adequate resources, resulting in reduced pup development and increased pre-weaning mortality rates.

In contrast with the mice in the present study, lactating sows lose BW during the lactation period, even under ad libitum feeding conditions (Noblet et al., 1998). Over the last few decades, (re)production levels of sows have been highly increased, whereas at the same time, sows in commercial production systems originate from genetically improved strains of lean pigs that have a decreased food intake capacity (Whittemore, 1996). Also, modern dairy cows have considerably lower food consumption than milk energy output in early lactation. Therefore, the initial production is achieved by a substantial mobilization of body reserves. It is only after 2 mo or more postpartum that a positive energy balance is regained (Knight, 2001). It is therefore expected that the negative resource balance in lactating modern livestock species is more negative than that modeled by mice in the present study.

	Implications

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Female mice that originate from a line selected for high litter size at birth produced larger litters relative to their body weight than an unselected control line. Apparently, milk production was not increased in proportion to their litter size and they were not able to support their litter as well as unselected control mice, resulting in reduced pup development and increased preweaning mortality rates. This implies that response to selection for high litter size leads to dams that produce larger litters than they can energetically support. In animal breeding, selection procedures must be considered that include selecting for the processes that support the litter (e.g., milk production and maintenance of the resource balance), or improvements will be necessary in the environment.

	Footnotes

 
¹ This study has been supported by a grant from the Norwegian Research Council, project No. 114258/111 and by the S. and M. Berges Forskningsfond. K. Kjus is gratefully acknowledged for her help in providing and maintaining the mice of the present study. Professor K. Hove and A. Haug are gratefully acknowledged for their suggestions on the method for obtaining the body composition samples. The Laboratory for Analytical Chemistry (LAK) in Aas, Norway, is acknowledged for the chemical analysis of the samples.

Received for publication May 22, 2002. Accepted for publication January 8, 2003.

	Literature Cited

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