Influences of prenatal and postnatal fraternity size on ovarian development in the mouse

An experiment was conducted to test effects of prenatal and postnatal fraternity size (size of litter in which an individual develops prenatally or is reared postnatally) on ovarian development in mice. Fraternity size treatments were created by standardizing sizes of prenatal and postnatal fraternities in which mice were gestated and reared. Prenatal fraternity size was standardized by surgery on Day 9 of gestation to 6, 10, and 14 fetuses. Postnatal fraternity size was standardized by randomly assigning pups to litters of 5, 10, or 15 pups within 24 h of birth. Female pups were killed at either 3 or 20 wk of age and right ovaries were prepared for histology. Follicles were classified by size and morphology, and numbers of follicles in each class were tabulated. Interaction of postnatal fraternity size and age was observed for number of antral follicles (p less than 0.05). Mice reared in small postnatal fraternities had more antral follicles at weaning (3 wk) and fewer antral follicles at maturity (20 wk of age) than mice reared in large postnatal fraternities. No effect of either prenatal or postnatal fraternity size on other follicle populations was observed (p greater than 0.20). Numbers of Type 2 (primordial), Type 3a, and Type 3b follicles changed with age (p less than 0.01); numbers of primordial follicles declined with age, but numbers of Type 3a and 3b follicles increased. A hypothesis of a negative association between postnatal fraternity size and number of antral follicles at 3 wk of age was supported, but a hypothesis of a positive association between fraternity size and number of primordial follicles was not supported.     

The effects of parity, litter size, season, and breeding protocol on the number of DBA/2J Ten mice available for weaning.

Data on the reproductive behavior of DBA/2J Ten mice, collected from October 1970 through March 1973 and utilizing a 2-female, 1-male breeding system, with the mice remaining together throughout their reproductive life indicates: a) Litter size tends to increase through the fourth litter, the first litter being much smaller than successive litters; b) Survival rates of litters with 2--4 pups increase with successive deliveries; c) Survival rates of litters with 5--9 pups are approximately the same regardless of parity; d) There is a circannual rhythm in the number of pups available for weaning da 21, which is attributable to changes in postnatal viability. Data collected using a breeding pen system, with isolation of females pre- and post-delivery (March 1973 to March 1974) indicates: a) There is a reduction in live litter sizes in later litters with this system; b) There is a large reduction in the proportion of pups surviving to weaning with this system when compared with the other breeding system.     

Effects of prenatal X-irradiation on the 14th-18th days of gestation on postnatal growth and development in the rat

Thirty-nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X-radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty-four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose-related weight reduction in term fetuses and offspring throughout the 86-day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose-related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose-related delay in appearance. These results indicate that fractionated exposure to X-radiation during the fetal period in the rat results in dose-dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long-range effects of prenatal exposure to ionizing radiation late in gestation.     

A reproductive study of Weiser-Maples guinea pigs]

The Weiser-Maples (WE) guinea pig strain was introduced by Backshire Co., Ltd. (USA) in 1977. We have been breeding WE strain guinea pigs for skin melanization research. The WE guinea pig colony produced 1271 pups in 417 litters from May 1978 through December 1983. Breeding date are shown below. The mean litter size was 3.05, the stillborn rate was 15.2%, the weaning rate for live-born pups was 93.5% and the sex ratio was 1.01. The average age at first vaginal membrane rupture was 31.4 days at which time body weight was 290.5g. The mean length of the first 7 estrous cycles was about 17 days, with no cyclical variation in length. The mean duration of gestation was 67.9 days. Duration of pregnancy varied with litter size. There was an inverse relationship between litter size and duration of pregnancy. Most of the pups were delivered alive in mid-pregnancy with a parturition range of 56 to 76 days. The probability of pup death depends on gestational length: the lowest incidence of mortality was seen in litters born at 70 days. The mortalities were related to litter size but not to parity. There was an inverse relationship between birth weight and litter size. In WE guinea pigs, the mean weight for a litter of 1 was 120 g; for a litter of 5, the mean body weight was 58g. Male body weights were slightly heavier than female at birth and at weaning age. The mean body weights are shown below, date of birth: female 88.3g, male 93.3g, weaning age (2 weeks): female 181.1g, male 198.8g and 30 weeks: female 758.7g, male 1018.0g. These date for WE guinea pigs are comparable to those of other strains.     

The effects of prenatal X irradiation on the appearance of reflexes and physiologic markers in the neonatal rat

Seventy pregnant adult Wistar strain rats were randomly assigned to 1 of 12 exposure groups; 9th or 17th day irradiation at the 0-, 0.1-, 0.2-, 0.4-, 0.6-, or 0.8-Gy dosage level. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter. A total of 508 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). A dose-response relationship for alterations in reflex acquisition and physiologic marker appearance was observed due to exposure above 0.2 Gy on the 17th day of gestation. Therefore, 0.2 to 0.4-Gy exposure may represent a threshold range for exposure on the 17th day using these postnatal parameters.     

Effects of litter size, age of young, and parity on foster mother behaviour in Rattus norvegicus

Maternal behaviour in the presence of newborn pups is determined by the age and size of the litter independent of parity of the mother, previous experience with different sized litters, and the number of days after delivery the measurements are taken. After fostering 10-day-old young, maternal behaviour is influenced by the age and size of the litter and also by the mother's previous experience with different sized litters.     

Reproductive patterns in the domestic dog--a retrospective study of the Drever breed

The aim of this study was to examine the differences, between seasons of the year, in the distribution of matings and whelpings, litter size, pup deaths, and sex ratio in domestic dogs. Furthermore, we wanted to examine the effects of age and parity of the bitch at the time of whelping on litter size, as well as the effect of litter size on gestational length. A final aim was to investigate the fertility and frequency of whelping problems in a private kennel of Drever dogs. Data from the Swedish Kennel Club (SKK) registry for the Drever breed during 1995-2006, comprising a total of 2717 litters, were analyzed together with more detailed data from a private, professional kennel of Drevers, with a total of 285 matings and 224 whelpings, during the same time period. The most matings took place during winter, and the fewest during summer; consequently, most whelpings occurred during the winter and spring seasons. Of the 285 mated bitches, 78.6% whelped, 6.25% experienced dystocia, and 5.36% underwent Cesarean section. The pup death rate was 7.6%. The largest litters were born during spring. Litter size was negatively correlated with duration of pregnancy (r=-0.18). Each pup more than average caused a shortening of the gestation by 0.25 days, and each pup less a corresponding lengthening. Bitches giving birth to their first litter after 4 years of age produced a smaller litter than younger bitches. Litter size decreased after 5 years in all bitches. The number of born pups at the private kennel increased from the first to the third parity, then decreased. The number of registered pups increased from the first to the second parity in the SKK data and from the second to the third parity in the data from the private kennel, then decreased. Mating a bitch only once resulted in a smaller litter size. None of the studied factors had any effect on the sex ratio of the pups. There were significant differences between males in whelping rate among the mated bitches, but no difference in mean litter size, which indicates a female problem rather than a male one. Available data suggest that the domestic dog is still under considerable seasonal influence, although modified by ambient and management factors.     

Genetic prenatal maternal effects on organ size in mice and their potential contribution to evolution

Two embryo transfer experiments were carried out in order to estimate the magnitude of prenatal maternal effects, independent of postnatal maternal factors, on the growth of internal organs and fat pads in mice. Reciprocal embryo transfers between the inbred mouse strains C3HeB/FeJ and SWR/J yielded three significant findings. First, all traits were not equally influenced by prenatal maternal factors. Genetic prenatal maternal factors, stemming from the genotype of the uterine mother, had a significant effect on testis weight, subcutaneous fat pad weight and epididymal fat pad weight in 21 day old progeny, but they had no effect on cranial capacity, an index of brain size, kidney weight, or liver weight. Prenatal litter size, defined as the sum of live and dead pups at birth, had a significant negative relationship with 21 day testis weight and kidney weight, and a significant positive association with subcutaneous and epididymal fat pad weights. Cranial capacity and liver weight at 21 days postnatally were not influenced by prenatal litter size. Second, the experiments demonstrated that there was ontogenetic variability in the strength of prenatal maternal effects. At 70 days of age, only subcutaneous fat pad weight was significantly influenced by genetic prenatal effects, and prenatal litter size had a significant negative relationship only with subcutaneous fat pad weight and body weight. Third, genetic prenatal effects had a significant influence on the among-trait covariances at 21 days postnatally, but not at 70 days. Because multivariate evolution involves covariances among characters, the latter results suggest that prenatal effects due to the mother's genotype can affect phenotypic evolution of mammals, especially for selection imposed early in life.     

Lifespan ontogeny of breeding and reproductive success in Mongolian gerbils

An analysis was made of demographic data collected from a colony of Mongolian gerbils (Meriones unguiculatus). The data on births of over 3800 gerbils provide evidence on several aspects of development and fecundity. Approximately 4% more females than males survived to weaning. Mean number of pups per dam per year was estimated to be 48.3, greater reproductive success than reported previously. The shortest period of gestation resulting in viable pups was 25 days. Implantation was delayed by the presence of suckling pups. When gestation was prolonged, there was a direct relationship between the number of pups being suckled concurrently and the length of the delay. Length of gestation did not affect the size of the subsequent litter. Female gerbils gave birth as early as 72 days of age. Gerbils continued to reproduce until after 2 years of age in some cases. There were fewer pups per litter born to older females, fewer pups per litter with increasing parity, and longer intervals between litters with increasing age.     

Effect of early fetal irradiation on the postnatal development of mouse.

BACKGROUND: An earlier study has shown that irradiation at the late fetal stage of Swiss albino mice disturbed postnatal growth and appearance of physiological markers. The present study was done to determine the effect of irradiation at the early fetal stage on the postnatal development of mouse. METHODS: Fourteen-day pregnant Swiss albino mice were exposed to 0.1-1.5 Gy of cobalt-60 gamma-rays. F1 pups were observed for < or = 6 weeks of age. Postnatal mortality, body weight and length, head length and width, tail length, and the time of appearance of physiological markers (pinna detachment, eye opening, fur development, vaginal opening and testes descent) were noted. RESULTS: There was no increase in congenital anomalies. Postnatal mortality and percentage of growth-retarded pups increased significantly at doses of 0.5-1.5 Gy. A significant delay in the appearance of all the physiological markers was also noted at these doses. Body length, head length, and tail length remained significantly lower than in the controls throughout the observation period at doses of 0.3-1.5 Gy, whereas body weight and head width showed such a persistent change only at > or = 0.5 Gy. CONCLUSIONS: The early fetal day 14 in mouse is sensitive to radiation-induced postnatal mortality and impairment of growth and temporal development of physiological markers, but not to induction of congenital anomalies. While mortality and physiological markers are not affected at <0.5 Gy, growth retardation appears to have a lower threshold of approximately 0.3 Gy.     

Difference in reproductivity and offspring growth between litter numbers in four strains of mice

As a means to improve mouse production, the differences among litter numbers in reproductivity, post-weaned growth and puberty of offspring were examined in 4 strains of mice, SHN/Mei, SLN/Mei, C3H/HeMei and GRS/AMei. Females were mated to be concurrently pregnant and lactating and reproductivity was recorded from the 1st to the 3rd litters. Some offspring of both sexes were weighed at 30, 40 and 50 days of age and vaginal opening was also checked in females. Pre-weaned growth of offspring differed little between litter numbers in all strains except GRS/A. Meanwhile, post-weaned growth of offspring was higher in the 2nd and 3rd litters than in the 1st litter of SHN and SLN, associated with a decreased rate of still-born pups. In C3H/He, post-weaned growth of offspring was higher in the 1st and 2nd litters and rearing rate decreased for the 3rd litter. In GRS/A, the 1st litter showed the greatest pre- and post-weaning growth rate of offspring. All findings indicate that in SHN and SLN strains the later litters are better for offspring production, while in C3H/He and GRS/A strains it is the earlier litters. The results stress the value of having information on reproductive characteristics of mouse strains for efficient offspring production.     

Do Laboratory Mouse Females that Lose Their Litters Behave Differently around Parturition?

Efficiency in laboratory mouse breeding is hampered by poor reproductive performance, including the loss of entire litters shortly after birth. However, the underlying mechanisms are not yet fully understood and establishing the cause of death in laboratory mouse pups can be complicated. Newborn mouse pups are generally hidden in nests, dead pups are often eaten by the female, and the widespread practice of leaving periparturient females undisturbed complicates inspection, which may delay the discovery of pup loss. In order to efficiently prevent problems with litter loss, it is important to find key factors for survival. We investigated differences in periparturient behavior between female laboratory mice whose pups survived until weaning and females whose entire litters were lost. Video recordings of 82 primiparous females of the C57BL/6 strain or knockouts with C57BL/6 background were used. The mice were observed from 24 h before until 24 h after parturition and female behaviors coded using a pre-established ethogram. The relationship between behavior and survival was analyzed using logistic models, where litter survival was regressed on the proportion of 30-s observations with at least one occurrence of the behavior. We found that females with surviving litters performed more nest building behavior during the last 24 h before parturition (p = 0.004) and spent less time outside the nest during the entire observation period (p = 0.001). Increased litter survival was also associated with more passive maternal behaviors and the female ignoring still pups less. Females that lost their litters performed more parturition-related behaviors, suggesting prolonged labor. The results indicate that maternal behavior plays a significant role in laboratory mouse pup survival. Complications at parturition also contribute to litter mortality.     

Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats

Postnatal early overnutrition (EO) is a risk factor for future obesity and metabolic disorders. Rats raised in small litters (SLs) develop overweight, hyperphagia, hyperleptinemia, hyperinsulinemia and hypertension when adults. As obesity is related to hyperleptinemia, leptin resistance and metabolic syndrome, we aimed to investigate body composition, plasma hormone levels, glucose tolerance and the leptin signaling pathway in hypothalamus from early overfed animals at weaning and adulthood. To induce postnatal EO, we reduced litter size to three pups/litter (SL), and the groups with normal litter size (10 pups/litter) were used as control. Rats had free access to standard diet and water postweaning. Body weight and food intake were monitored daily, and offspring were killed at 21 (weaning) and 180 days old (adulthood). Postnatal EO group had higher body weight and total and visceral fat mass at both periods. Lean mass and serum high-density lipoprotein cholesterol (HDL-C) were higher at 21 days and lower at 180 days. Small litter rats presented higher levels of globulins at both periods, while albumin levels were higher at weaning and lower at adulthood. There was higher leptin, insulin and glucose serum concentrations at 21 days old, while no glucose intolerance was observed in adulthood. Leptin signaling pathway was unaffected at weaning. However, postnatal EO induced lower JAK2 and p-STAT3, and higher SOCS3 expression in adult animals, indicating central leptin resistance in adulthood. In conclusion, postnatal EO induces obesity, higher total and visceral fat mass, lower HDL-C and central leptin resistance in adult life.     

Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii)

Background

Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10–12) and small (3–4) litter sizes, of Brandt''s voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China.

Methodology/Principal Findings

Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters.

Conclusions/Significance

These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.     

Prenatal epidemiology of spontaneous cleft lip and palate, open eyelid, and embryonic death in A/J mice.

Nongenetic bases of variability in the frequencies of spontaneous cleft lip and palate (CLP), open eyelid (OL), and fetal resorption were searched for in A/J mouse litters of prenatal ages 17-21 days post-VP and parities 1-7. The malformation rates did not decrease with advancing fetal age, and hence prenatal elimination does not account for the lower rates seen in newborns. Multivariate analysis indicated that the frequencies of CLP and resorption were inversely related to maternal age and directly related to litter size, and that the frequency of OL was related, directly, only to litter size; but that none were associated with maternal weight, parity, and several other variables. Regarding uterine location, the frequency of CLP was higher at the ovarian and cervical sites, OL higher at the cervical site, and resorption lower at the ovarian site, than elesewhere. CLP was significantly commoner in females, and OL commoner in males; also, since the percentage of males increased with parity, the frequency of CLP in males relative to that in females decreased with parity, and that of OL increased. Malformed offspring weighed less than normal ones; and the sex with the lower frequency of CLP or OL had the greater weight reduction. The results are discussed in relation to the frequency of malformations in human fetuses and newborns.     

A retrospective study of infant mortality of cotton-top tamarins (Saguinus oedipus) in captive breeding

Fifty of 156 (32%) colony bred cotton-top tamarins were stillborn, and 31 (20%) died within the first week after birth. The stillbirth rate was related to litter size and parity in captivity. A higher percent of single births were stillborn (69%) compared to those of twin births (26%) (p less than 0.005). A higher percent of infants born of the first litter in captivity (42%) were stillborn than those of subsequent litters (23%) (p less than 0.025). Stillbirths were not related to season of birth or sex of infant. Survival of live infants was unrelated to season of birth, sex, litter size, or number of litters.     

Effects of age and parity on litter size and offspring sex ratio in golden hamsters (Mesocricetus auratus)

Golden hamsters that were mated repeatedly from 55 days of age produced 6-12 litters. Litter size at birth rose between the 1st and 2nd litters, peaked on the 3rd, and declined steadily after the 5th litter. Offspring sex ratio (% male) at birth followed a similar pattern: increasing between the 1st and 2nd litters, remaining high through the 3rd, and becoming increasingly female-biased thereafter. Weaning success decreased sharply after the 6th litter and most dams failed to raise any young to weaning after the 9th litter. These sequential effects on litter size, offspring sex ratio and weaning success were also observed in females mated once at different ages, but they occurred considerably later in life, i.e. increasing parity hastened the effects of advanced age. These age- and parity-related changes in litter composition are consistent with the Trivers-Willard hypothesis that physiologically-stressed females would skew offspring sex ratios to favour daughters. However, since the observed changes in sex ratio were probably due to differential prenatal mortality, their adaptive significance is unclear.     

Swine generated by somatic cell nuclear transfer have increased incidence of intrauterine growth restriction (IUGR)

While somatic cell nuclear transfer (SCNT) has been successful in several species, many pregnancies are lost and anomalies are found in fetal and perinatal stages. In this study SCNT and artificial inseminations (AI) populations were compared for litter size, average birth weight, piglets alive at birth, stillborn, mummies, dead at the first week, intrauterine growth restriction (IUGR) and large for gestational age (LGA). Twenty-three SCNT litters (143 individuals) were compared to 112 AI litters (1300 individuals). Litter size average was 11.5 for AI and 6.2 for SCNT. Litter weight and average birth weight adjusted by litter size were significantly (p < 0.05) higher in AI than in SCNT litters. The SCNT population had a significant (p < 0.01) increase in the number of IUGRs per litter with LSmeans 7.2 +/- 1.4 versus 19.4 +/- 3.5 and means 8.0 +/- 10.8 versus 15.5 +/- 24.5 for AI and SCNT, respectively. Additionally, there was a trend for higher postnatal mortality and stillbirths in the SCNT population. These findings demonstrate that there are some differences between SCNT-derived and AI litters. SCNT-derived pigs are excellent models to study epigenetic factors and genes involved in IUGRs, and to develop effective means to improve fetal growth in humans and animals.     

Cross-generational effect of prenatal morphine exposure on neurobehavioral development of rat pups

Prenatal exposure to opiates can have devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. The present study was aimed at identifying cross-generational effects of prenatal morphine exposure in Sprague-Dawley rats. Pregnant rats were injected subcutaneously with either saline or morphine (10 mg/kg) twice daily during gestational days 11-18. Litter size, percentage of males and females, anogenital distances (AGDs), righting reflex, and body weight were assessed in prenatally morphine-exposed pups (first generation) and their offspring (second generation). Both prenatally morphine-exposed pups and offspring of prenatally morphine-exposed dams exhibited an increased latency to right. Additionally, second generation pups were slower in righting than first generation pups. During the early postnatal period the second generation pups weighed less than the first generation regardless of drug exposure. The AGDs of second generation male pups were decreased relative to the first generation. Our data provide important novel information about the trans-generational effects of maternal opiate abuse that may be useful for understanding/evaluating the teratogenic effects of prenatal opiate exposure.     

The effect of overfeeding the young in early postnatal ontogeny on brown fatty tissue

We studied the effects of overfeeding of neonatal Wistar rats on O2 consumption by the interscapular brown adipose tissue and DNA content in the tissue. The overfeeding was induced by reducing the litter size to two to three pups per dam compared with standard litters of five to ten pups. All animals were allowed free access to water and forage and were kept at 24 +/- 1 degrees C. Newborn and 16-day-old rat pups were used in the experiments. The body weight of overfed pups was significantly higher than that of standard fed pups (p < 0.001). There were no differences between groups of 16-day-old rats in the resting metabolic rate. The mass of dried brown adipose tissue relative to the body mass in overfed pups was lower than in the control pups (p < 0.01). O2 consumption in the rats from small litters was 35% higher (p < 0.001). DNA content (mg/g brown adipose tissue) in overfed rats was 35% lower as compared to the control pups (p < 0.001). These results indicate that overfeeding at the preweaning stage of life affects growth, cellularity, and thermogenic function of brown adipose tissue.