Intrauterine position modulates maternal behaviors in female mice

Intrauterine position (IUP), the proximity of a fetus relative to same and opposite sex fetuses, is a reliable predictor of the direction and intensity of social and regulatory behaviors in adult male and female mice. In the present experiment, female Rockland-Swiss (R-S) mice who had resided in utero between two females (OM) and females who had resided between two males (2M) were compared with respect to five indices of maternal behavior: Spontaneous parental responses exhibited toward neonates; nestbuilding during pregnancy; aggression during pregnancy; aggression during lactation; and reproductive/lactation performance. There was no significant difference between 0M and 2M females in their spontaneous parental responses toward neonates or their level of nestbuilding behavior during pregnancy. However, when tested for aggression during pregnancy and lactation, 2M females exhibited aggression on a greater number of test days during pregnancy than did 0M females. Also, during pregnancy and lactation, 2M females displayed more lunges and attacks toward adult male intruders than 0M females. Although 0M females tended to have larger litters than 2M females, the animals did not differ with respect to any other measure of reproductive/lactation performance. Intrauterine position, therefore, modulates some aspects of maternal behavior but apparently not others.     

Psychosocial maternal stress during pregnancy: effects on reproduction for F0 and F1 generation laboratory rats

The impact of daily social maternal stress on reproduction parameters was studied in F0 and F1 generation female Long-Evans rats. Chronic maternal stress was induced in pregnant females (F0 females) by 2 h social confrontation with a dominant female throughout pregnancy. Social stress of F0 females was associated with lower maternal body mass investment in litters. While maternal stress did not cause a decline in the F0 female mass, it resulted in reduced litter sizes and lower litter masses. The individual body mass of offspring from stressed (= prenatally stressed offspring, PS) and control F0 generation mothers (= prenatal control offspring, PC) did not differ at birth. However, PS offspring grew faster during lactation and were therefore heavier than PC offspring at weaning. Reproduction parameters of F1 generation females were determined until an age of 180 days. Investigation revealed that PS females did not differ from PC females in any reproduction parameter assessed, except for higher PS offspring body mass at birth. It was also observed that a higher percentage of PS females gave birth outside the core breeding period during the light (= inactive) period. This study shows that exposure to a relatively mild social stressor during pregnancy alters female reproduction in rats. However, there was no indication of higher infant mortality which is often associated with severe laboratory stress. We argue that the reduced litter sizes in stressed F0 mothers represent an adaptive strategy from an evolutionary point of view.     

Effects of stress during pregnancy on maternal behavior in mice

The effects of stress experienced during pregnancy and raising stressed offspring on maternal behavior were investigated in Swiss-Webster mice. Dams were either stressed or not stressed during pregnancy, and raised either prenatally stressed or nonstressed cross-fostered pups. Maternal behaviors such as grooming, nursing, pup retrieval and maternal aggression were assessed during the first 4 days after birth. Nonstressed dams raising stressed pups and stressed dams raising nonstressed pups groomed and nursed their pups significantly less than did control dams (stressed dams raising stressed pups and nonstressed dams raising nonstressed pups). Nonstressed dams raising stressed pups were also the slowest to retrieve both the first and last pup in retrieval tests. Nonstressed dams raising nonstressed pups were significantly less aggressive than other dams. In contrast, stressed dams raising stressed pups exhibited high levels of nursing and grooming, retrieved their pups rapidly and were very aggressive towards an intruder. These results indicate that raising stressed pups, or experiencing stress during a pregnancy can have significant effects on maternal behaviors. Stressed dams raising stressed pups exhibit maternal care comparable to that of nonstressed dams raising nonstressed pups at least for nesting/nurturing behaviors, and show increased levels of aggression and pup retrieval.     

Effects of social stress and intrauterine position on sexual phenotype in wild-type house mice (Mus musculus)

Wild-type house mice were used to test the effect of intrauterine position on anogenital distance (AGD) and to verify whether crowding stress would masculinize female pups, developing at all intrauterine positions, as has been demonstrated in CF-1 mice stressed by restraint, heat, and light. Stress of crowding was documented by comparing aggressive behavior, litter birth weights, and plasma corticosterone levels among females in different densities. AGDs were recorded from pups born to females housed from day 12 to 19 of gestation either individually with their mate (nonstressed) or in one of two group-housed densities. Female pups from nonstressed dams positioned between two males in utero (2M females) had longer AGDs than females positioned between two females (0M females). AGDs of males from nonstressed dams did not differ on the basis of intrauterine position. Group-housed pregnant females in the higher of two densities had female pups with longer AGDs than female pups of other dams. However, variance in female pup AGD was no different among dams in different densities. These results extend to the wild house mouse previous findings in albino mice that intrauterine position influences sexual phenotype. In addition, social stress can induce masculinization of female pups in wild mice as physical stress has been shown to do in albinos. This suggests that intrauterine position effects and their modification by crowding stress can potentially influence the dynamics of wild house mouse populations.     

Prenatal stress eliminates differential maternal attention to male offspring in Norway rats

Maternal licking behavior was observed in 20 Long-Evans rat dams on two consecutive days. Stimulus pups were male and female foster pups from dams that were either housed with 5 adult males during the last trimester of pregnancy (stressed) or housed alone (unstressed). Unstressed male pups received significantly more maternal licking than their female siblings, but prenatally stressed males and females received similar levels of maternal licking, comparable to that directed to unstressed females. In a second study, urine collected from prenatally stressed male pups elicited significantly less investigation from dams in a choice test than urine from age-matched unstressed males. It is concluded that the chemosignals which stimulate dams normally to provide more maternal attention to male than female neonates are deficient in prenatally stressed males. The results raise the possibility that differential maternal care may mediate some effects of prenatal stress on behavioral development in males.     

Activation of aggression in female rats by normal males and by castrated males with testosterone implants

Female hooded rats were continuously housed with an intact male, a castrated male with subcutaneous testosterone implants, or two other females. At weekly intervals over a 10-week period, the cagemate(s) and pups were removed and aggression by the female toward an unfamiliar female intruder was observed over a 15-min period. On the 11th week each female was subjected to this intruder test in an unfamiliar cage. On the 12th week, a final test was conducted in each female's living cage with a male rather than a female as the intruder. The aggressive behaviors recorded were attacks, bites, on-top, and piloerection. Females housed with normal males displayed a significant increase in aggression prior to parturition. Their aggressiveness persisted through the 10th test with peaks at parturition and the start of lactation. Females housed with castrated males also displayed significant increases in aggression but without the peaks associated with parturition and lactation. Their aggressiveness also persisted throughout the test period. Females housed with other females showed a small increase in aggression over weeks. All groups showed virtually no aggression in the unfamiliar cage. All females displayed some aggression toward a male intruder but the level of aggression was highest in maternal females. The results demonstrate that aggression qualitatively similar to that displayed following parturition and during lactation can be elicited in nulliparous females.     

Serum corticosterone in fetal mice: sex differences, circadian changes, and effect of maternal stress.

The serum concentration of corticosterone was examined in control and stressed pregnant female mice (Mus domesticus) as well as male and female fetuses due to our interest in the behavioral effects of material stress on offspring in mice. Pregnant females were restrained under flood lights (2 sessions/day, 45 min/session) from Day 13-17 of pregnancy. On Day 17 of pregnancy a significant increase in maternal serum corticosterone was exhibited 1 h after the onset of a stress session, and serum corticosterone did not return to baseline until 16 h later. We also observed a significant increase in serum corticosterone in male fetuses during the first 4 h after maternal stress, while no significant change in serum concentration of corticosterone was observed in female fetuses throughout 24 h after maternal stress. Daily variation in serum concentration of corticosterone was also determined at 4-h intervals in pregnant mice and their fetuses from Day 16-18 of pregnancy. Pregnant females maintained on a 12 L:12 D cycle exhibited peak serum corticosterone concentrations at and just before the onset of the darkness. Daily fluctuations in serum concentrations of corticosterone in male and female fetuses reflected the pattern observed in the mothers. A sex difference in serum corticosterone in fetuses was observed at some, but not all times of the day, with the difference being greatest during the dark phase of the mother's light:dark cycle.     

Prepartal chronic stress increases anxiety and decreases aggression in lactating female mice.

The effects of two types of prepartal chronic stress on maternal behavior, anxiety, and maternal aggression during lactation were assessed in female outbred Swiss mice. Two groups (n = 18 each) were subjected to 10 consecutive daily sessions of restraint stress (RS) or novel environment stress (NES) from Day 4 to Day 14 of pregnancy. A third group (n = 18) was left undisturbed during pregnancy (controls, C group). All females underwent a maternal behavior test (10-min observation after separation and reunion with the pups) on Postpartum Day (PD) 1, an anxiety test (a light-dark conflict test) on PD 6, and a maternal aggression test (5-min exposure to an unfamiliar adult male) on PD 7. NES and RS groups tended to show higher amounts of maternal care. Anxiety increased in the stressed females compared with controls, whereas the opposite was true for maternal aggression. In the RS group, anxiety was negatively correlated with maternal aggression. These results suggest that chronic stress may have produced neuronal and endocrine alterations in the dams, which may have led to increased avoidance of aversive stimuli. The results also support the hypothesis that, in lactating mice, anxiety is inversely related to the probability of displaying intense forms of aggression.     

Litter deficits of socially stressed and low status hamster dams

The effects of maternal social stress, induced by pairing pregnant females, and social status, measured by agonistic behavior within pairs, on pup development was investigated in hamsters. Using litters from untreated first pregnancies as a control, 40 dams were housed either alone or paired with another dam during their second pregnancy. Within a pair, the dam with more aggressive and fewer defensive responses than the other was considered dominant. Compared to their first unpaired litters, second litters of paired dams were smaller in number. Comparisons among second litters showed that paired dams, especially submissive dams, had fewer pups than unpaired dams. It was concluded that both maternal social stress and low status increase intrauterine mortality.     

Prenatal stress modifies behavior in offspring of bank voles (Clethrionomys glareolus)

The aim of the present study was to investigate the effect of prenatal stress on behavior of adult bank vole males and females. Pregnant females were submitted to stress by short encounters of two females at the same stage of pregnancy, to crowded condition by transfer to a cage with four to five nonpregnant females, or stressed by immobilization. The stressors were applied on Days 13, 14, and 15 of pregnancy. The results indicate that prenatal stress influenced adult offspring behavior tested in the presence of the same sex, as compared to controls. Females and males differ in their reactions to stress. Prenatal stress decreased the nonaggressive behavior of females but males did not change their amicable approaches toward males. In bank vole males, prenatal social or immobilization stress increased aggression, but females made more attacks only after prenatal stressing by immobilization. This indicates that in bank vole females classical stressor involved different mediators from those associated with prenatal social stresses. Our results indicate that prenatal stress in bank voles decreases the social activity of female offspring and increases aggression in male offspring. Social stress applied to females in late pregnancy may increase the number of aggressive males in a population.     

Prenatal stress affects the rate of sexual maturation and attractiveness in bank voles

Field studies reveal that bank vole females' mobility and aggression increase during pregnancy. Here we investigated the reaction of pregnant females to social stress evoked by short but frequent meetings with another female at the same stage of pregnancy. The stress neither evoked pregnancy termination nor affected pregnancy duration but had a long-term effect on the reproductive activity of the offspring. Prenatal stress reduced the rate of sexual maturation of voles as estimated at the age of 20 days. Uterine weights of prenatally stressed females and testes weights of prenatally stressed males were significantly lower than in offspring born to nonstressed mothers. Olfactory signals are known to be important in the sexual preferences of bank voles. Adult prenatally stressed females were more attractive to other adult females than were nonstressed animals. For bank vole males, however, prenatal stress decreased the attractiveness of females; adult males selected nonstressed females over stressed partners, by odor. This study shows that prenatal conditions evoked by short but frequent encounters with another pregnant female lead to delayed puberty in females and males, and decrease sexual attractiveness in adult offspring. These two negative effects may significantly limit the reproduction of prenatally stressed offspring.     

Low temperatures during early development influence subsequent maternal and reproductive function in adult female mice

Challenging conditions early in development can have enduring effects into adulthood. The effects of low temperatures were examined on subsequent sex-specific morphology (anogenital distance [AGD]), maternal care, and reproductive performance in adult female mice. Dams (F0) were maintained either in (1) standard laboratory room temperatures (21 +/- 2 degrees C) or (2) low temperatures (10 +/- 2 degrees C) throughout gestation. Their progeny (F1) either remained in the temperature condition in which they were conceived or were switched to the other temperature condition at 2 days of age until weaning. Reproductive performance and maternal behaviors were assessed in adulthood. F0 dams that were maintained in low temperatures bore larger litters as compared to F0 animals housed in standard temperatures throughout their pregnancy. In contrast, mean litter size was reduced for all groups of F1 females that experienced low temperatures. Infant mortality was elevated in litters of F1 females that were exposed to low temperatures both before and after birth. Prenatal exposure to low temperatures was associated with reduced responsiveness towards the nursing young and decreased maternal aggression in F1 animals. Prenatally treated F1 females had longer, male-like AGDs on Day 2 following birth compared to animals not subjected to experimental manipulations. Our results indicate that exposure to low temperatures during early development impairs reproductive function and is associated with important fitness costs as evidenced by reduced offspring survival. Our findings also suggest that chronic low temperatures experienced only after birth may have less deleterious effects than exposure to a combination of pre- and postnatal or prenatal treatments alone.     

Intermale and maternal aggression in adult rats tested at different ages

In Experiment 1, rat colonies consisting of two males and one female were established when the animals were either 100, 200, or 300 days old. All colony members were reared from weaning in small, stable isosexual groups prior to colony formation. Males that were 200 days old engaged in significantly more fighting at colony formation, and, three weeks later, were more likely to wound an intruder during a 24 hr aggression test than either younger or older animals. These findings demonstrate that colony aggression in male rats varies markedly as a function of age when reared under housing conditions that are employed in most laboratories. In Experiment 2, colony females were individually housed after their second pregnancy and their response to a male intruder was evaluated for a 24 hr period after nine days of lactation. Maternal aggression occurred at all ages, indicating that age may be of lesser importance in nest defense of females than intermale conflict. However, maternal aggression was ineffective in preventing the destruction of a high proportion of the litters by intruders in the three maternal age groups.     

Changes in responsiveness to newborn pups in pregnant,nulliparous golden hamsters

Virgin female hamsters were mated and tested once daily for maternal retrieving behavior beginning on days 0, 5, 9, 13, 15, of the 16 day gestation period to determine if responsiveness toward newborn pups changes as pregnancy proceeds. Upon initial exposure to 3 newborn pups, only a small percentage of early-to-mid-pregnant females exhibited maternal retrieving behavior spontaneously. In contrast, over half of the 15 day pregnant females displayed retrieving during the first test. Despite the high frequency of initial pup-directed aggression and cannibalism, maternal retrieval was induced in the majority of the females in all groups by repeated daily exposure to 3 newborn pups. However, no significant differences were observed in the number of pup exposure periods required to induce maternal retrieving in 0, 5, and 9 day pregnant females. It is concluded that the high level of maternal responsiveness observed in the parturient hamster develops somewhat abruptly during late pregnancy. In this respect, the pattern observed in the hamster differs from the more gradual increase in maternal responsiveness reported in mid-to-late-pregnant mice and rats.     

The effects of intrauterine position on competition and behavior in the mouse

The purpose of the present study was to examine the effect of intrauterine position on: (1) competition for limited food resources when the animals were previously deprived of food; (2) social preference for a male during various phases of the estrous cycle; and (3) social and sexual behavior when the animals were provided with like-treated females or receptive females, respectively. Females developing in utero between two males (2M females) and females developing between two females (0M females) were different on only one measure recorded during the competition for limited food, i.e., gaining control of the food pellet, with the 0M females outcompetiting the 2M females. When given a choice between a male or a female neither 2M or 0M females in estrus showed a preference for the male. The results also indicated that 2M females were significantly more aggressive and more likely to show male sexual behavior when compared to 0M females.     

Prenatal stress feminizes juvenile play patterns in male rats.

Sexually dimorphic rough-and-tumble play patterns were compared in male and female rats derived from control mothers and mothers stressed from days 14-21 of pregnancy. Animals were weaned into groups of 8 consisting of 2 males and 2 females from each treatment. Play in the home cage was recorded at 25, 28, 31, 34, 37 and 45 days of age and was most intense on day 31. The overall level of play was significantly higher in control males than in females or stressed males. Control males showed higher levels of the pinning component of rough-and-tumble play than females or stressed males. No play partner preferences were detected in any group. In adulthood, a higher percentage of stressed than control males displayed the female lordotic pattern. No deficits in ejaculatory behavior occurred in the stressed males. Since maternal stress alters patterns of plasma testosterone in male fetuses, the data suggest that the sexual differentiation of social play begins during prenatal ontogeny in the rat. The present results show that sexually dimorphic behaviors displayed before puberty are incompletely masculinized in prenatally stressed males, a finding similar to that reported for a number of adult behaviors.     

Suppression of adult copulatory behaviors following LiCl-induced aversive contingencies in juvenile male rats

Sexually immature juvenile male rats received an injection of .3 M (20 ml/kg) lithium chloride (LiCl) during each of 8-10 pairings (spaced at 2-3-day intervals) with an estrous female. Approximately seven weeks later, these males displayed fewer copulatory behaviors in pairings with estrous females than saline control rats. Noncontingent .3 M LiCl injections administered to juvenile males did not affect adult copulatory behaviors. Males that were either group or individually housed during the retention interval displayed comparable suppression, which suggests that copulatory suppression does not represent a generalized aversion to social interactions with another animal. Males housed during the retention interval in an environment that contained the odors of estrous females also displayed suppression comparable to that of males housed in the absence of such odors. This suggests that the associations that mediate copulatory suppression are not elicited solely by the odor cues of estrous females. These data demonstrate that LiCl-induced aversive contingencies in juvenile male rats subsequently suppress adult copulatory behaviors.     

Effects of siblings on reproductive maturation and infanticidal behavior in cooperatively breeding Mongolian gerbils

Mongolian gerbils living with their natal families undergo delayed reproductive maturation while helping to rear their younger siblings, whereas those housed away from their natal families may mature earlier but often respond aggressively to unfamiliar pups. We tested whether cohabitation with pups contributes to reproductive suppression and inhibition of infanticidal behavior, using young males and females housed with (1) their parents and younger siblings (pups), (2) parents without pups, (3) mixed-sex littermate groups, or (4) mixed-sex groups of unrelated peers. Maturation in males was inhibited by cohabitation with the parents, while maturation in females was further suppressed in the presence of pups. Males in all housing conditions showed little aggression towards unfamiliar pups, whereas females were usually infanticidal unless housed with pups. Aggression toward pups was especially pronounced in females that were pregnant or undergoing ovulatory cycles. Thus, cohabitation with younger siblings may intensify reproductive suppression and inhibit infanticidal behavior in female gerbils, whereas male gerbils exhibit parentally induced reproductive suppression and low rates of infanticide even in the absence of younger siblings.     

Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep

Experimental elevation of maternal testosterone (T) from 30 to 90 days of gestation leads to intrauterine growth retardation (IUGR) and increased prepubertal growth rate in female lambs. This study tested the hypothesis that prenatal T treatment during mid-gestation alters the trajectory of the fetal insulin-like growth factor (IGF)–insulin-like growth factor binding protein (IGFBP) system to promote IUGR and subsequent postnatal catch-up growth in female lambs. Plasma IGF-I and IGFBPs were measured by radioimmunoassay and Western ligand blot, respectively, on 65, 90 and 140 days (d) of gestation, at birth, ∼5 months (prepubertal, the catch-up growth period), and ∼9.5 months (postpubertal). Northern blot analysis was used to measure hepatic mRNA content of IGF system components during fetal stages. At fetal 65 d, plasma protein and hepatic mRNA content of IGFBP-1, an inhibitor of IGF bioactivity, was elevated in prenatal T-treated fetuses although body weight did not differ. There was a transient increase in plasma IGF-I and IGFBP-3 concentrations at fetal 90 d in prenatal T-treated fetuses. Hepatic IGF-I mRNA and plasma IGFBP-3 content were reduced by 140 d when body weight was reduced in prenatal T-treated fetuses. Plasma IGFBP-2 content was significantly reduced in prenatal T-treated newborns, but by 4 months these females had significantly higher circulating IGF-I and IGFBP-3 concentrations and faster growth rates than control females. After puberty, plasma IGF-I remained elevated in prenatal T-treated females. These findings provide evidence that prenatal T excess programmes the developmental trajectory of the IGF/IGFBP system in female sheep to reduce IGF bioavailability during IUGR and increase IGF bioavailability during prepubertal catch-up growth.     

Prenatal stress affects mother-infant interaction in Norway rats

Pregnant Long-Evans rats were stressed by crowding, and subsequent mother-infant interactions were described after cross-fostering. Prenatally stressed pups elicited less maternal licking from unstressed foster dams than controls, and previously stressed dams licked unstressed foster pups less than controls. No other differences in mother-infant interactions were detected. Adult offspring reared by foster dams that were stressed during pregnancy were more active in an open field than controls, but prenatally stressed and unstressed animals reared by control dams did not differ. Thus, stress during pregnancy can alter the maternal behavior of stressed dams, and the differential maternal stimulation can affect adult open-field behavior. Because prenatally stressed pups elicit different maternal care, cross-fostering does not eliminate the possibility that maternal stimulation may mediate some prenatal stress effects.