LH receptor induction and ovulation rate in mice selected for litter size and body weight

Female mice from lines which had undergone long-term single trait and antagonistic index selection for litter size and body weight were analysed for ovulation rate and LH receptor induction. Compared to randomly selected controls, selection for large litter size increased ovulation rate (60%; P less than 0.001) and decreased LH receptor induction per microgram ovarian DNA (87%; P less than 0.01). Selection for large body weight increased ovulation rate (18%; P less than 0.001), but did not lead to a significant correlated response in LH receptor induction. Index selection for large litter size and small body weight increased ovulation rate (14%; P less than 0.01) and decreased LH receptor induction (72%; P less than 0.01), while index selection for small litter size and large body weight did not significantly alter either ovulation rate or LH receptor induction. LH receptor quantities in testes of males from the 5 lines did not exhibit the among-line profile which was observed in ovaries of females. These results confirm the role of ovulation rate in mediation of the positive genetic correlation between litter size and body weight in mice. Increased ovulation rate in mice selected for large litter size may be due to mechanisms associated with LH receptors as well as factors related to growth. In contrast, increased ovulation rate in mice selected for large body weight may be due exclusively to factors related to growth.     

Genetic variation in spontaneous ovulation rate and LH receptor induction in mice

Selection for litter size (Line S1) and for post-weaning body weight gain (Line G) increased spontaneous ovulation rate in mature females by 69 and 73%, respectively, over that of randomly bred control mice (Line C). Inbreeding from S1 mice with selection for litter size produced highly inbred lines with elevated ovulation rates. Inbreeding from Line C mice produced a 21% divergence among lines, but did not depress the mean ovulation rate. Crosses of these lines revealed little heterosis in ovulation rate. LH receptors were induced by treating females from 22 days of age with diethylstilboestrol for 4 days and FSH for 2 days. The in-vitro binding of 125I-labelled hCG per microgram DNA decreased 56% in response to selection for litter size and increased 57% in response to selection for body weight gain, indicating high susceptibility of this trait to genetic change. Inbreeding from Line C mice produced a 135% divergence amongst lines, but did not depress the mean LH receptor induction. Body weight had significant effects on ovulation rate and LH receptor induction. These results show that selection for litter size and for rapid post-weaning body weight gain increases ovulation rate, but we suggest that different mechanisms are involved in these responses.     

Changes in the kinetics of follicular growth in response to selection for large litter size in mice

The present study examined a randomly selected control line (C) and a large litter size-selected line of mice (S1) to determine changes in the kinetics of follicular growth that have occurred in response to selection for large litter size. For each follicle type (FT), the number of healthy and atretic follicles, length of components of granulosa cell cycle, follicular growth rate, and follicular flux were determined microscopically from serially sectioned ovaries of Lines C and S1 mice. Selection for litter size significantly increased the number of small and medium, and some large follicle-size classes. While selection for litter size did not change the overall incidence of atresia at proestrus, it did decrease the incidence of atresia in the large Type 7 follicles by 19%. Selection for litter size also increased ovarian weight at proestrus. Selection for litter size increased the rate of growth through FT 3a, 5a, and 5b, and reduced the time required for follicles to grow from primordial to Graafian follicles from 39.1 days in Line C to 33.4 days in Line S1. Selection for large litter size also increased the flux of follicles through follicle Types 3a to 5b by 72%, and through follicle Types 6 and 7 by 21%. Genetic variation was found in many aspects of the kinetics of follicular growth.     

Effects of three methods of selection for litter size in mice on pre-implantation embryonic development.

Characteristics of preimplantation embryonic development to Day 3.5 of gestation were evaluated in lines of mice after 21 generations of selection for litter size or components of litter size. Selection criteria were direct selection for number born (LS), selection on an index of ovulation rate and the proportion of ova shed that resulted in fully formed pups (IX), selection for number born in unilaterally ovariectomized females as an indication of uterine capacity (UT), and an unselected control (LC). Comparison of the average distributions of embryonic stage of development on the left side of the uterus showed that selection (average effect of LS, IX, and UT vs. LC) tended to advance (p = 0.07) the average stage of embryonic development at Day 3.5 and shift the distribution (p = 0.10) by increasing the frequency of expanded blastocysts and decreasing the frequency of pre-morula embryos. A similar shift in the distribution on the right side of the uterus was not statistically significant. Selection decreased (p = 0.06) variability in developmental stage among embryos within the right uterine horn. These selection criteria evaluated in the mouse appear to have changed the frequencies of genes that affect some determinants of average stage of embryonic development and uniformity of development within a uterine horn at Day 3.5 of gestation.     

Is the reproductive potential of wild house mice regulated by extrinsic or intrinsic factors?

Abstract The regulation of reproductive performance in small mammals may be determined by extrinsic or intrinsic parameters. In a large‐scale, replicated field experiment we monitored the seasonal fluctuation in food availability and tested the effects of food addition on the reproductive performance of wild house mice (Mus domesticus) in south‐eastern Australia. Ovulation rates and litter size increased during spring and peaked in October/November. Ovulation rate was consistently higher than litter size by approximately 1.2 embryos (19%). None of the extrinsic parameters measured (food quality and quantity, mouse abundance) had an impact on reproductive performance. The addition of food did not prevent the mid summer decrease in ovulation rates nor did it alter the difference between ovulation rates and litter size. While the number of previous pregnancies did not affect reproductive performance, the age of mice did: older mice tended to have higher ovulation rates than younger mice. The effect of age‐dependent changes in ovulation rates on population growth rates of house mice seemed to be of limited importance. We conclude that the reproductive output in wild house mice is determined by ovulation rates and not by litter size. The regulation of ovulation rates through an intrinsic factor (age) seems evident but the importance of food availability and house mouse abundance for ovulation rates is low.     

Direct responses in males and correlated responses for reproduction in females to selection for testicular size adjusted for body weight in young male lambs

Selection based upon testicular diameter adjusted for body weight at 6, 10 and 14 weeks of age was used to produce two lines of sheep, with either high or low testicular size. Ten generations of selection were carried out and the estimate of the realized heritability of the selection criterion was 0.53 +/- 0.01. There were significant positive correlated responses to selection for testicular diameter at 6, 10 and 14 weeks of age, but the correlated responses in body weight at these ages were negative. In mature females, there were significant negative correlated responses to selection in premating body weight in the 1st, 2nd and 3rd breeding season and in the day of the first oestrus in the 2nd breeding season. Litter size per ewe mated had a small positive correlated response to selection in the second breeding season. This latter response appeared to be due to a positive correlated response in fertility, ewes from the High-line having a significantly higher probability of conceiving to a single mating than those from the Low-line. There was no significant correlated response in ovulation rate or litter size per ewe lambing and the genetic correlation between these traits and the selection criterion is likely to be close to zero. This may be due to the adjustment for body weight used, but it is possible that, in any event, body weight in young rams may be a better predictor of female ovulation rate than testicular diameter. These results do not rule out the possibility that testicular size in rams older than those selected would provide a good predictor of genetic merit for female ovulation rate.     

Genetic control of survival of frozen mouse embryos

Lines of mice selected for increased litter size (L+), increased body weight (W+), or randomly (K) were used to study genetic variation in embryo cryosurvival in response to standard cryopreservation protocols. A total of 60528-cell embryos from 400 females were used in two studies. In Study 1, embryos from L+, W+, and K were frozen by slow-cool and ultrarapid (direct-plunge) methods to evaluate effects of selection on cryosurvival and genotype X freezing method interaction. Post-thaw survival (PTS) was measured as percentage of recovered embryos developing in vitro to blastocyst per donor female. Nonfrozen control embryos developed similarly for each line. Within slow-cool freezing, lines differed (W+ greater than K, W+ = L+, L+ = K; p less than 0.05); no differences were observed within the ultrarapid freezing. However, line X method interaction effects on PTS were not significant. In Study 2, reciprocal crosses were made between L+ and K and between W+ and K. Hybrid and pure line embryos were frozen by slow-cooling. Control embryos developed similarly for all genotypes. Selection lines did not differ for overall PTS. However, hybrid embryos from L+ dams were superior to those from K dams (84 vs. 61%; p less than .001). No overall embryo heterosis was observed. Differences were not significant among embryo genotypes or treatments for cell number or in vivo survival. These results demonstrate significant correlated responses in embryo post-thaw cryosurvival due to selection, and implicate both maternal and embryonic genomes as controlling mouse embryo cryosurvival.     

Correlated responses to artificial body size selection in growth, development, phenotypic plasticity and juvenile viability in yellow dung flies

Most life history traits are positively influenced by body size, whereas disadvantages of large body size are poorly documented. To investigate presumed intrinsic costs of large size in the yellow dung fly (Scathophaga stercoraria; Diptera: Scathophagidae), we established two replicates each of three body size laboratory selection lines (small, control and large; selection on males only), and subjected flies of the resulting extended body size range to various abiotic stresses. Response to selection was symmetrical in the small and large lines (realized h(2) = 0.16-0.18). After 24 generations of selection body size had changed by roughly 10%. Female size showed a correlated response to selection on male size, whereas sexual size dimorphism did not change. Development time also showed a correlated response as, similar to food limited flies, small line flies emerged earlier at smaller body size. At the lowest larval food limit possible, flies of all lines emerged at the same small body size after roughly the same development time; so overall phenotypic plasticity in body size and development time strongly increased following selection. Juvenile mortality increased markedly when food was extremely limited, large line flies showing highest mortality. Winter frost disproportionately killed large (line) flies because of their longer development times. Mortality at high temperatures was high but size-selective effects were inconsistent. In all environments the larger males suffered more. Initial growth rate was higher for males and at unlimited food. Small line individuals of both sexes grew slowest at unlimited larval food but fastest at limited larval food, suggesting a physiological cost of fast growth. Overall, extension of the natural body size range by artificial selection revealed some otherwise cryptic intrinsic juvenile viability costs of large size, mediated by longer development or faster growth, but only in stressful environments.     

Environmental networks,compensating life histories and habitat selection by white-footed mice

Summary Analysis of 6 years' data on a population of free-living white-footed mice documents both phenotypic and environmental control of litter size. Litter size was positively correlated with maternal body size. Maternal size depended upon both seasonal and annual variation. Paradoxically, the proportion of small versus large litters varied among habitats independently of the effects of body size. The result is an influence of habitat on life history that yields patterns of reproduction and survival opposite to the predictions of demographic theory. The habitat producing the largest litters had a relatively high ratio of adult/juvenile survival. Litter size was small in the habitat where the adult/juvenile survival ratio was smallest. All of these anomalous patterns can be explained through density-dependent habitat selection by female white-footed mice. Life-history studies that ignore habitat and habitat selection may find spurious correlations among traits that result in serious misinterpretations about life history and its evolution.     

Restricted selection index in mice designed to change body fat without changing body weight: correlated responses

Summary Correlated responses were studied in lines of mice selected for eight generations based on the criterion of a restricted selection index. Two replicate lines were selected in each treatment as follows: HE, high epididymal fat pad weight (EF) with zero change in body weight (BW) at 12 weeks of age; LE; low EF with zero change in BW; and RS, randomly. Correlated responses showed considerable variation between replicates, suggesting that genetic drift was important. Further, correlated responses for most traits were relatively small, probably because of low selection intensity. The HE line responded as expected in component traits of the restricted index. Associated compositional traits in HE responded as predicted since traits correlated with adiposity increased and hind carcass weight did not change significantly. Feed intake increased and feed efficiency (weight gain/feed intake) decreased in HE, as predicted. In contrast, the LE line did not respond in component traits as predicted since EF did not decrease and BW increased. Consequently, LE exhibited little change in traits associated with adiposity, but hind carcass weight, feed intake and feed efficiency increased. Of the correlated responses scored for fitness traits (littering rate, number of days from pairing of mate to littering, litter size and preweaning pup survival rate), significant effects were found for decreased littering rate in LE and increased prenatal survival rate in HE. In summary, correlated responses to restricted index selection generally agreed with expectation when responses in component traits of the index were considered.The research reported in this publication was funded by the North Carolina Agricultural Research Service (NCARS), Raleigh, NC 27695-7643, USA. The use of trade names in this publication does not imply endorsement by the NCARS, nor criticism of similar ones not mentioned     

Effects of Population Size and Selection Intensity on Correlated Responses to Selection for Postweaning Gain in Mice

Correlated responses to selection for postweaning gain in mice were studied to determine the influence of population size and selection intensity. Correlated traits measured were three-, six- and eight-week body weights, litter size, twelve-day litter weight, proportion infertile matings and two indexes of reproductive performance. In general, the results agreed with observations made on direct response: correlated responses in the body weight traits and litter size increased as (1) selection intensity increased and (2) effective population size increased. Correlated responses in the body weight traits and litter size were positive in the large population size lines (16 pairs), as expected from the positive genetic correlation between these traits and postweaning gain. However, several negative correlated responses were observed at small population sizes (one and two pairs). Within each level of selection intensity, traits generally associated with fitness tended to decline most in the very small populations (one and two pairs) and in the large populations (16 pairs) for apparently different reasons. The fitness decline at the small effective population sizes was attributable to inbreeding depression. In contrast, it was postulated that the fitness decline at the large effective population size was due to selection moving the population mean for body weight and a trait positively correlated genetically with body weight (i.e., percent body fat) away from an optimum.     

Mammalian reproductive strategies: A generalized relation of litter size to body size

Summary A generalized relationship of litter size to mammalian body size was predicted by a graph model. The model was used to generate hypotheses explaining specific features of variation in gestation time, relative litter weight, birth weight, and reproductive capacity. The predictions were tested by means of data from the literature.Mammals were assumed to maximize neonatal survival of offspring to the limits allowed by litter weight per female body weight. Gestation time correlated negatively with the foetal growth rate of relative litter weight. Gestation time did not correlate with the foetal growth rate of individual offspring.Relative litter weight correlated negatively with adult body weight. This relationship was explained by the higher assimilation rate per unit weight relative to metabolic rate in small mammals.Birth weight correlated positively with body weight. However, small mammals produce larger offspring than predicted by the linear relationship of birth weight to body weight in large mammals. There is obviously a minimum birth weight which cannot be decreased without special arrangements for parental care.The prediction of the relationship of litter size to body size was derived from the relations of relative litter weight and birth weight to body weight. In small mammals (less than 1 kg) litter the correlation was negative. When litter size was compared with body length, the correlation was positive in small mammals (less than 30 cm) and negative in large mammals. In both sets of data there was a negative overall correlation between litter size and body size.Reproductive capacity, defined as the number of offspring per season, correlated negatively with life-span.     

The influence of parity and maternal preimmunization on fetal survival in mice

It is known that as parity increases, cell-mediated immunity to paternal antigens increases in mice. The article reports an experiment designed to compare the results of normal parity with artificial immunization simulating maternal sensitization to paternal antigens in mice. Virgin females were immunized at weekly intervals by intraperitoneal injections of 50 mcl of heparinized blood from males with whom they would eventually be mated. The immunized virgins and multiparous females were mated for 4 to 6 weeks after their last injection or litter. The total and live litter size increased with immunization; the total size with natural parity also increased though the live litter size slightly decreased with parity. The mean fetal death rate was relatively the same for both groups. Fetal weight increased with parity but not change was observed in placental weight. Both fetal and placental weight did not change with immunization. There was no increase in the expected number of male fetuses. The increased litter size in the immunized group may be due to increased ovulation rates.     

Caterpillars selected for large body size and short development time are more susceptible to oxygen‐related stress

Recent studies suggest that higher growth rates may be associated with reduced capacities for stress tolerance and increased accumulated damage due to reactive oxygen species. We tested the response of Manduca sexta (Sphingidae) lines selected for large or small body size and short development time to hypoxia (10 kPa) and hyperoxia (25, 33, and 40 kPa); both hypoxia and hyperoxia reduce reproduction and oxygen levels over 33 kPa have been shown to increase oxidative damage in insects. Under normoxic (21 kPa) conditions, individuals from the large‐selected (big‐fast) line were larger and had faster growth rates, slightly longer developmental times, and reduced survival rates compared to individuals from a line selected for small size (small‐fast) or an unselected control line. Individuals from the big‐fast line exhibited greater negative responses to hyperoxia with greater reductions in juvenile and adult mass, growth rate, and survival than the other two lines. Hypoxia generally negatively affected survival and growth/size, but the lines responded similarly. These results are mostly consistent with the hypothesis that simultaneous acquisition of large body sizes and short development times leads to reduced capacities for coping with stressful conditions including oxidative damage. This result is of particular importance in that natural selection tends to decrease development time and increase body size.     

Influence of early pregnancy on reproductive rate in lines of mice selected for litter size

Summary The influence of male-induced early puberty on female reproductive rate was determined in three lines of mice differing in litter size and body weight. The lines originated from a single base population and had undergone 20 generations of selection for the following criteria: large litter size at birth (L⁺), large litter size and small 6-week body weight (L⁺W^–), or small litter size and large 6-week body weight (L^–W⁺). Females were paired with a mature intact male of the same line at 3, 5 or 7 weeks of age. Mean mating age, averaged over lines, was 26.5 ± .3, 38.3 ± .3 and 52.7 ± .3 days. Exposure to a mature male accelerated female sexual maturation in each line. When contrasted with their sibs mated at a later age, early-pregnant females from each line exhibited a decline in one or more component of reproductive performance, suggesting that the physiological state of the very young female was not optimum for normal pregnancy. In comparisons of early and later mating ages, all three lines showed a decreased littering rate at first mating, number born alive, and individual birth weight of progeny adjusted for litter size; L⁺ and L⁺W^– mice showed an increased perinatal mortality rate; L⁺ and L^–W⁺ had a reduction in litter size at birth. When the L⁺, L⁺W^– and L^–W⁺ lines were compared with an unselected strain and a line selected for high postweaning gain in similar experiments, a genotype by environment interaction was apparent since all lines did not respond in a similar manner to early mating. The line ranking for litter size at birth for each age at male-exposure was L⁺>L⁺W^–>L^–W⁺, despite the significant line by age interaction. When litter size was adjusted by covariance for body weight at mating, the significant effects of age at male-exposure and line by age interaction were eliminated. All fertile females were remated after they had weaned their first litter to obtain information on litter size in parity two. Line differences in litter size at birth and number born alive were uniform across parities. An age by parity interaction was evident since the decreased fecundity at younger ages of male exposure in the L⁺ and L^–W⁺ litters of parity one was not evident in parity two. Litter feed efficiency during first parity gestation was defined as litter birth weight divided by either cumulative feed intake of the dam from mating to parturition (GEI) or cumulative feed intake from weaning to parturition (GEII). The ranking of lines for GEI and GEH was L⁺> L⁺W^–>L^–W⁺, but when feed efficiency was adjusted for littering rate, L⁺W^– and L^–W⁺ were not significantly different. With regard to age at mating, the ranking for GEI (7 wk > 5 wk > 3 wk) was reversed from GEII (3 wk >5 wk > 7 wk) and these significant differences were maintained after adjustment for littering rate.Paper No. 6302 of the Journal Series of the North Carolina Agricultural Research Service, Raleigh. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Research Service of the products named, nor criticism of similar ones not mentionedOn leave at the Institute of Animal Genetics, West Mains Road, Edinburgh EH9 3JN, Scotland. Supported, in part, by an Underwood Fund Fellowship, Agricultural Research Council, and an Edinburgh University Biological Fellowship in the Department of Genetics     

Is there a relationship between prion protein genotype and ovulation rate and litter size in sheep?

The identification of an association between polymorphisms of the prion protein (PrP) gene and susceptibility to scrapie has enabled the development of breeding programmes to increase natural resistance to scrapie. It is, however, imperative to identify if such selection would affect important reproduction and production traits. The objective of this study was to determine if there is a relationship between polymorphisms at codons 136, 154 and 171 of the PrP gene and ovulation rate or litter size in sheep. Data were collected from a mixed-aged flock of Belclare ewes, over a 9-year period. Ovulation rate was determined annually using laparoscopy by counting the number of corpora lutea at each of two consecutive oestrous cycles, one immediately before and one after mating (2418 records from 366 ewes). Litter size was recorded at parturition (875 records from 353 ewes). The five common PrP alleles were present in the population and 14 PrP genotypes were represented among the animals studied. There was no significant overall effect of PrP genotype on ovulation rate or litter size and pairwise comparisons among genotypes did not reveal any significant differences for either trait. These data suggest that breeding programmes based on selection for specific polymorphisms of the PrP gene will not influence ovulation rate or litter size, at least in the breed studied.     

Selection on predicted breeding value for milk production delays ovulation independently of changes in follicular development, milk production and body weight

Two studies were conducted to investigate the effect of selection on predicted breeding value (PBV) for milk production, and its associated metabolic and endocrine milieu, on follicular development and ovulation in the postpartum period. A total of 71 cattle from lines selected to differ in their PBV were used in two consecutive years. In Study 1 the first ovulation and commencement of normal luteal function occurred significantly earlier in low (L) line cows than high (H) line cows. In Study 2 average daily milk production during the study period did not differ (P>0.10) between cows in either the H (=31.0+/-1.5kg/day) or L (=30.2+/-1.7kg/day) PBV lines although, 305 days milk production was significantly different (P<0.01; H=6880+/-164kg versus L=5795+/-317kg). As in Study 1, first ovulation postpartum in Study 2 occurred earlier (P<0.01) in the L (day 19) versus the H line (day 28). Circulating concentrations of glucose and insulin were significantly lower, whilst concentrations of GH and BOHB were higher in cows from the high PBV line. No differences in gonadotrophin concentrations were seen between lines. Both changes in body weight and patterns of follicle development did not differ between lines. By day 15 postpartum all cows had follicles of all three-size categories (small, medium-sized and large). Small (P<0.07) and medium-sized follicle numbers increased (P<0.01) with day postpartum. However, the inclusion of predicted changes in body weight as a covariate in the analysis, demonstrated that changes in number of small and medium-sized follicles were associated with changes in body weight. In conclusion, selection on PBV for milk production is associated with a longer interval from parturition to first ovulation, independent of changes in follicular development, milk production and body weight implicating other factor(s) associated with genetic selection.     

Bayesian inference of genetic parameters and selection response for litter size components in pigs.

Three contemporary lines were formed from the progeny of 50 French Large White sows. In the first line, gilts were selected for ovulation rate at puberty. In the second line, they were selected for prenatal survival of the first two parities, corrected for ovulation rate. The control constituted the third line. Ovulation rate at puberty was analyzed using an animal model with a batch effect. Prenatal survival was analyzed with a repeatability animal model that included batch and parity effects. Flat priors were used to represent vague previous knowledge about parity and batch effects. Additive and residual effects were represented assuming that they were a priori normally distributed. Variance components were assumed to follow either uniform or inverted chi-square distributions, a priori. The use of different priors did not affect the results substantially. Heritabilities for ovulation rate ranged from 0.32 to 0.39, and from 0.11 to 0.16 for prenatal survival, depending on the prior used. The mean of the marginal posterior distribution of response to four generations of selection ranged from 0.38 to 0.40 ova per generation, and from 1.1 to 1.3% of the mean survival rate for average survival per generation.     

Unrearable litters and prenatal reduction of litter size in the common marmoset (Callithrix jacchus).

It is widely believed that common marmosets (Callithrx jacchus) typically give birth to twins under natural conditions. In captivity, however, births of triplets or even larger litters are common, although parents rarely succeed in rearing more than two offspring. The traditional interpretation is that captive conditions, notably the ready availability of food, have led to increased reproductive output, perhaps involving a higher ovulation rate. The present paper provides evidence, combined from ultrasound examinations between ovulation and birth and hysterotomies conducted during the late embryonic and early fetal phase, that the litter size can be progressively reduced during pregnancy without spontaneous abortion. There is an unusually long lag phase prior to the onset of embryonic growth in common marmosets; the fetal stage does not begin until day 80 of the 144-day pregnancy. Reduction in litter size occurs during embryonic stages (up to day 80), and continues into the fetal stages. These results indicate that the common marmoset is adapted for flexible modification of litter size between ovulation and birth. The high incidence of triplet births in captive colonies may therefore be an expression of an adapted natural developmental process under artificial circumstances.