EFFECTS OF POSTNATAL LITTER SIZE ON REPRODUCTION OF FEMALE MICE 1

Transcription

1 EFFECTS OF POSTNATAL LITTER SIE ON REPRODUCTION OF FEMALE MICE 1 R. E. Nelson 2 and O. W. Robison North Carolina State University, Raleigh 2767 SUMMARY A group of 8 dams weaned 588 female mice to be mated and allowed to reproduce. These females were assigned at birth to be reared in a litter of eight or 14 mice. Such litters were intended to represent postnatal environments equivalent to small and large litters. However, average litter sie was approximately 15 mice in this line and comparisons were more correctly those between small and average litter sies. A slight bias, genetically in favor of females raised in large litters, was noted due to allotment. A sample of 123 females was slaughtered at 1 days of pregnancy and 325 were allowed to litter. Body weights at 12, 21 and 42 days were positively correlated with each other and with reproductive traits. Weights at 12, 21 and 42 days were consistently larger (P.1) for females raised in small litters. Sexual maturity (days to vaginal opening) was negatively associated with weights to 42 days. Mice raised in litters of eight were earlier maturing (2.11 days) and reached maturity at heavier weights (1.61 g). These differences (P.1) indicate that age at maturity could not be completely explained by weight differences. An advantage (P.5)in corpora lutea numbers (.3) was found for females from small litters. The advantage for number of embryos at 1 days of pregnancy was only.48 and was not significant. Females from small litters had.31 and.23 more mice born and mice born alive, respectively, but these differences were not significant. Heritability estimates for litter sie born, numbers born alive and litter weight were.34,.48 and.64, respectively, when calculated for females from small litters. The corresponding Paper No. 475 of the Journal Series of the North Carolina Agricultural Experiment Station, Raleigh. 2Present address: Kleen Leen Inc., Cedar Rapids, Iowa. estimates were.4,.4 and.36 for females reared in litters of 14. Strong indications of a negative relationship between litter environment and genetic potential to reproduce were noted. A major component of this relationship was mediated through weight up to 42 days. Improvement of reproductive traits through control of litter environment may be indicated. (Key Words: Postnatal Environment, Litter Sie, Reproduction, Female Mice.) INTRODUCTION Improvement of reproductive traits through selection is a difficult task. Litter sie has been relatively stable within breeds of swine for many years. Attempts at increasing litter sie have been unsuccessful but the potential for increased production has kept interest in its improvement high. The laboratory mouse is a species that can be used to explore means of genetically improving litter sie in the pig. Whether or not findings of experiments using the mouse can be directly applied to swine is not completely known. However, characteristics of littering, mothering behavior and suckling competition are similar. Taking advantage of these similarities may greatly increase the efficiency of studying swine reproduction. Cox et at. (15) found postnatal maternal influence to be the single most important factor determining body weight through weaning in mice. The importance of these maternal components in growth traits has been supported by Rutledge et al (172), Eisen (17), E1ksh et at. (167) and Young et al (165). LaSalle and White (175) and Nagai (175) pointed out the important positive association between weight gain and subsequent reproduction and maternal influence. Since weights and gains of the mouse and pig are very important to increased reproductive performance, environmental factors involved with mothering ability and litter sie that reduce gains would be deleterious. Eisen (173) 824 JOURNAL OF ANIMAL SCIENCE, Vol. 42, No. 4

2 POSTNATAL LITTER SIE ON REPRODUCTION IN MICE 825 and Revelle and Robison (173) have suggested that the covariances between direct genetic and maternal effects were large and negative in mice and swine, respectively. Females born into large litters with potential to be good mothers and bear large litters are subjected to an adverse environment of competition for milk and attention. This antagonism could be a major component in keeping heritability of reproductive traits low and contribute to the lack of improvement through selection. This study was initiated to investigate the effects of postnatal environment, mediated through divergent litter sies, on the subsequent reproduction of females. MATERIALS AND METHODS Second parity female mice were used as the dams in this study. These mice were taken from a randombred control line (ICR) maintained in the mouse colony of the North Carolina State University Animal Science Department. The females were randomly mated to contemporary males and allowed to litter. Upon littering, two dams were paired randomly as long as age differecnes between their offspring did not exceed 24 hours. Litter weights and offspring numbers were recorded at birth. The offspring within each pair were then reallotted to the dams so that a litter of eight and a litter of 14 mice were formed. These litters contained approximately equal numbers of mice from each dam. Female offspring were used preferentially in these allotments with males filling out the litters to the desired sie. Litter weights of the newly formed groups were taken at this time. Individuals were toe clipped at 12 days and individual weights were recorded at 12, 21 and 42 days. Male and female mice were weaned and separated at 21 days. Females were placed in groups of four per cage. Age at vaginal opening was used as a measure of the onset of puberty. At 6 weeks of age, these females were placed with unrelated contemporary males and information on their reproductive performance was recorded. A portion of these females was slaughtered at 1 days of pregnancy for observation of corpora lutea and embryo numbers. Analyses were by least squares procedures as described by Harvey (175). These chiefly consisted of fitting the following model: Yijk~ =/t + a i + bij + c k + (ac)ik + (bc)ij k + eijk ~, where Yijk~ = the individual observation made for a given dependent variable, /~ the overall mean, a i = the random effect of the i th pairing, bij = the random effect of the jth genetic dam within the i th pairing, Ck = the fixed effect of the k th litter sie as reared, (ac)ik and (bc)ij k = the interaction effects and eijkq = the random component. This model yielded analyses of variance as shown in table 1. In many cases, interactions were not significant and were pooled with error. Daughter-dam regressions, within litter sie as reared, yielded heritability estimates for number born, number born alive and litter birth weight. RESULTS AND DISCUSSION A total of 588 female mice were weaned from 8 dams in this study. Means and standard deviations of traits associated with their birth and subsequent allotment are shown in table 2. The values are presented for each litter sie as reared. No significant differences in number born, number born alive and litter weight as born were detected between females raised in litters of eight or 14 mice. There was an indication that females allotted to large litters TABLE 1. ANALYSIS OF VARIANCE Source df E(MS) Pairs i-1 Genetic mothers/pairs.~ (j--l) Litter sie as reared 1~-1 Pair litter sie as reared a (i-1)(k-1) Genetic mother litter sie as ]~ (j-1)(k-1) reared/pair i Error remainder Ge 2 + KBaGM/P 2 + K o'~ 2 a e 2 + K7 ~GM/P (72 e + K4OGMxLS/P 2 + Ksop 2 S + K6 (~S a e K2aGMxLS/P + K3apxLS K~ OGMxLS/P awhen significant, this term was used as error in testing litter sie as reared.

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4 POSTNATAL LITTER SIE ON REPRODUCTION IN MICE 827 were born in slightly larger litters and any bias was genetically in their favor. Not all mice could be carried to term but weight and vaginal opening measurements taken from all females agree well with the random sample data for those slaughtered and those allowed to litter. Least squares means and standard errors of weights up to 6 weeks of age, days to vaginal opening and weight at vaginal opening are presented in table 3. Females raised in litters of eight mice had consistently larger (P.1) weights up to 42 days. The magnitude of this advantage was only 2.52 g at 42 days vs 3.2 g at weaning (21 days), indicating some compensatory gain. Monteiro and Falconer (166) indicated similar compensatory growth after weaning. Days to vaginal opening showed (P.1) earlier onset of puberty (2.11 days) for mice in small litters. Body weights at vaginal opening were smaller for females from large litters indicating that puberty was not strictly weight dependent. Despite being older, females raised in litters of 14 mice were lighter at vaginal opening. Therefore, maturity could not adequately be measured by weight. It should be pointed out that age at vaginal opening is an index of puberty but is not identical with first estrus. Falconer (155) inferred that the effect of mothering ability on the individual was made up of a component related to anatomical development and sie as well as a component involved in physiological efficiency. A sample of 123 pregnant females was slaughtered on the 1th day of pregnancy. The information obtained from these mice is presented in table 4. Body weights followed the same trends established for all females (table 3). Days to vaginal opening, however, were more divergent between litter sies (3.3 days). An advantage of.3 corpora lutea (P.1) was found for females from small litters. Embryo numbers at 1 days of pregnancy showed a similar trend between the litter sie groups but the magnitude of the difference was only one-half that for CL (.48) and was not significant. Land and Falconer (16) found heritabilities for ovulation rate of.22 and.31 in nulliparous and primiparous female mice, respectively. Increased ovulation rate due to selection did not result in significant increases in litter sie under natural conditions. Some correlated response in litter sie was found when selection was made in lines where females were superovulated. Bradford (168, 16) also D [-.1.1 ii d ~ ~ ~.~ on~ ~'~ ~ ~ ~,, ~ O

5 828 NELSON AND ROBISON selected for ovulation rate and embryo survival to 16 days under natural and superovulation conditions. Ovulation rate lines responded to selection but litter sie was not increased. Increased survival rates were improved through selection and subsequent litter sies increased. Bradford stated that selection for litter sie increased ovulation rate but not the reverse. Litter information was obtained from 325 females and is presented in table 5. Again, weights and vaginal opening traits showed results comparable to the entire group of females. No significant differences in reproduction were found for females raised in litters of eight or 14 mice. Advantages of.31 mice born and.23 mice born alive were not significant. It should be pointed out that females in the foundation groups littered approximately 15 mice (table 2). This was not taken into consideration in determining the large litter sie to be studied. The competition of 14 mice per litter probably was not sufficient to evoke measurable deleterious effects. Comparisons should more correctly be viewed as those between small and average litter sies. Table 6 contains the phenotypic correlations estimated among the various traits. These are partial correlations calculated after adjustment for the effect of litter sie as reared. Weights to 42 days were all positively correlated. Weight at 42 days showed less association with 12- and 21-day weights than the 12-, 21-day weight correlation. Days to vaginal opening was negatively correlated with these weights with faster growing mice maturing earlier. Weight at vaginal opening had a positive association with weight characteristics up to 42 days and a correlation of.6 with days to vaginal opening. This indicates that even though rapid growth to weaning and large weights at that point reduced days to puberty, females reaching maturity slowly were also reaching heavier weights. Monteiro and Flaconer (166) found age at vaginal opening to be attained at approximately the same weight over widely varying ages. However, Synenki et al. (172) found that mice growing more rapidly to a constant age (7 days) also mature earlier. The partial correlations of this study suggest that management procedures for increasing gain might decrease the age at vaginal opening and increase litter sie. Days to vaginal opening was significantly associated with reproductive performance only when measuring offspring litter weight. This was probably due to females being at least 6 r~,v.1 ~4 ii oo g, ~ "O O "O

6 POSTNATAL LITTER SIE ON REPRODUCTION 1N MICE 82 b. O O M m u M E- k) > C > F- d~ " ' ' 1 ' " ~ mo o E It.E d II ~Su. -~ o N ~,,~'~ ~.~ ~-o ~.~, ~ k~ weeks of age prior to mating. Weight at vaginal opening was positively associated with corpora lutea and embryo numbers but this association was smaller for littering traits. Corpora lutea and embryo numbers were correlated with all weights. Offspring number and offspring alive had similar but smaller correlations with these weights. Rahnefeld et al (166) estimated the genetic correlation between postweaning gain and litter sie to be.8. Selection for postweaning gain increased litter sie by. mice per generation for 2 generations. Hanrahan and Eisen (174) estimated a genetic correlation of.58 for these traits in the randombred population that provided females for this study. Bradford (171), however, doubled weight gain between 21 and 42 days in 23 generations of selection to find litter sie unchanged. Ovulation rate was increased but embryo survival decreased. Falconer (165) estimated heritability of litter sie to be.56 and suggested litter standardiation. Eisen (17) found a heritability of.24 for this trait in standardied litters. Bradford (168) selected two lines for litter sie using standardied litters (1 mice) to get realied heritabilities of.13 and.44. Falconer (16) reported realied heritability estimates for litter sie of.8 in upward selection and.23 in downward selection lines. In this study, danghter-dam regressions for 165 females raised in small litters and 16 females raised in large litters yielded heritability estimates for litter traits. Heritabilities from females raised in litters of eight mice were.34,.48 and.65 for number born, number born alive and litter weight, respectively. Heritabilities measured from females raised in litters of 14 mice were.4,.4 and. 36 for the respective traits. Heritabilities such as these could explain some of the negative response to selection that Falconer (155) reported for litter sie in the initial generation. The environment that selected females were exposed to at suckling had a deleterious effect on their reproductive performance. Revelle and Robison (173) also found heritability of litter sie estimates for swine to be different when calculated within small (.2), medium (.1) and large (-.13) litters. This is a strong indication of large negative covariances between direct and maternal effects. Reproductive performance of the female mouse may be more responsive to selection when litter sie, during rearing, is controlled.

7 83 NELSON AND ROB1SON Results presented are actually based on comparisons of females raised in small and average litter sies. Litters of 14 mice probably do not place stress on the individual mouse at an intensity found in litters chosen under selection. Certainly, potential litter sies for selection in these mice would be somewhat above 15 mice per litter. These females were not mated until at least 6 weeks of age which gave considerable time for all females to mature. Despite these complications, many differences were noted between the litters of eight and 14 mice and may be indicators of the environmental influences associated with this trait. The regression of reproductive traits studied on weaning weights showed weight to be very important. The results are in good agreement with Revelle and Robison (173) who showed only small differences in litter traits of females from small and average litters. They also showed similar delays in puberty when litter sies increased. Heritability estimates are very strong indicators of potential improvement through selection. This avenue for improvement should be explored further and utilied if present. LITERATURE CITED Bradford, G. E Selection for litter sie in mice in the presence and absence of gonadottopin tteatmenl Genetics 58:283. Bradford, G. E. 16. Genetic control of ovulation rate and embryo survival in mice. I. Response to selection. Genetics 61:5. Bradford, G. E Growth and reproduction in mice selected for rapid body weight gain. Genetics 6: 4. Cox, D. F., J. E. Legates and C. Clark Cockerham. 15. Maternal influence on body weight. J. Anim. Sci. 18:51. Eisen, E. J. 17. Maternal effects on litter sie in mice. Can. J. Genet. Cytol. 12:2. Eisen, E. J Direct and maternal genetic responses resulting from selection for 12-day litter weight in mice. Can. J. Genet. Cytol. 15:483. El Oksh, H. A., T. M. Sutherland and J. S. Williams Prenatal and postnatal maternal influence on growth in mice. Genetics 57:7. Falconer, D. S Patterns of response in selection experiments with mice. Cold Sp. Harbor Symposia on Quant. Biol. 2:178. Falconer, D. S. 16. The genetics of litter sie in mice. J. Cell. Comp. Phy~ 56:143. Falconer, D. S Maternal effects and selection response. In S. J. Geerts ed. Genetics Today, Proc 11th Intern. Congr. Genet. Pergamon Press, New York. Hanrahan, J. P. and E. J. Eisen Genetic variation in litter sie and 12-day weight in mice and their relationships with post-weaning growth. Anim. Prod. 1:13. Harvey, W. R Least-squares analysis of data with unequal subclass numbers. USDA, ARS H-4. Laad, R. B. and D. S. Falconer. 16. Genetic studies of ovulation rate in the mouse. Genet. Res. 13:25. LaSalle, Timothy J. and John M. White Characteriation of response to selection for growth and maternal ability in laboratory mice. J. Anim. Sci. 4:48. Monteiro, L. S. and D. S. Falconer Compensa: tory growth and sexual maturity in mice. Anim. Prod. 8:17. Nagai, Jiro, C. G. Hickman and G. R. BAIT Selection index based on the nursing ability of the mother and the mature weight of the offspring in mice. J. Anim. Sci. 4:5. Rahnefeld, G. W., R. E. Comstock, Madho Singh and S. R. NaPucket Genetic correlation between growth rate and litter sie in mice. Genetics 54:1423. Revelle, T. J. and O. W. Robison An explanation for the low heritability of litter sie in swine. J. Anita. Sci. 37:668. Rutledge, J. J., O. W. Robison, E. J. Eisen and J. E. Legates Dynamics of genetic and maternal effects in mice. J. Anim. Sci. 35:11. Synenki, R. M., E. J. Eisen, G. M~/trone and O. W. Robison Thyroid activity in lines of mice selected for large and small body weight. Can. J. Genet. Cytol. 14:483. Young, C. W., J. E. Legates and B. R. Farthing Prenatal and postnatal influences on growth, prolificacy and maternal performance in mice. Genetics 52:553.