Paradoxical effects of maternal stress on fetal steroids and postnatal reproductive traits in female mice from different intrauterine positions

We examined effects of maternal stress on prenatal serum concentrations of testosterone and estradiol and on postnatal reproductive traits in female mice from different intrauterine positions. On Day 18 of fetal life, control females positioned in utero between two male fetuses (2M females) had higher concentrations of testosterone and lower concentrations of estradiol in serum than control female fetuses located between two females (0M females). Control females positioned between a male and a female fetus (1M females) had intermediate levels of both hormones. Prior intrauterine position in control females accounted for differences in genital morphology (length of the anogenital separation) at birth and length of estrous cycles during adulthood. Maternal stress eliminated these postnatal differences due to prior intrauterine position: all 0M, 1M, and 2M female offspring of stressed mothers exhibited postnatal traits that were indistinguishable from those of control 2M females. Maternal stress resulted in an increase of over 1 ng/ml in serum testosterone in all female fetuses; the magnitude of the increase was similar for 0M, 1M, and 2M females. There was no effect of maternal stress on serum concentrations of estradiol in 0M and 2M female fetuses. Maternal stress resulted in a dramatic change in the postnatal traits of 0M females, whereas 2M females showed no change. Since the effect of maternal stress on sex steroids was similar among fetuses from different intrauterine positions but postnatal response to maternal stress varied by intrauterine position, other components of the endocrine system may mediate effects of maternal stress on these postnatal characteristics.     

Prior intrauterine position influences body weight in male and female mice

In two longitudinal studies, intrauterine location of male and female Rockland-Swiss mice relative to fetuses of the same and opposite sex dramatically influenced body weight. In one study, body weight of males and females that were located in utero between two female fetuses (OM animals) or between two male fetuses (2M animals) was assessed from birth to the time of weaning (25 days of age). The body weights of 2M females were indistinguishable from those of OM and 2M males on all but a few of the 25 postnatal days of life. Also, 2M females were significantly heavier than OM females from Postnatal Day 6 onward, and 2M males weighed significantly more than OM males from Postnatal Day 19 onward. In a second study, food intake and body weight of animals from different intrauterine locations were examined from 25 to 120 days of age. Regardless of prior intrauterine position, males were always heavier than females. However, prior in utero location modulated body weight in that 2M females were significantly heavier than OM females and 2M males were reliably heavier than OM males. Intrauterine position effects were observed in the absence of any appreciable influence of this variable on levels of food intake. Taken together, the results suggest that prior in utero location may influence metabolic set points involved in the regulation of body weight and fat storage.     

Long-term effects of accelerated or delayed sexual maturation on reproductive output in wild female house mice (Mus musculus)

The effects of acceleration and delay of puberty in female house mice on survival and reproduction were tested using 6 experimental groups: (1) control females mated at the time of first oestrus, (2) females mated at weaning, (3) females treated with male urine starting at weaning and mated at first oestrus, (4) females housed in groups and mated at first oestrus, (5) females housed alone, treated with urine from grouped females and mated at first oestrus, and (6) females housed alone and mated at 68 days of age. Females caged with males at weaning or treated with male urine and mated at puberty had lower rates of survival to 180 days of age, but did not differ in rates of fertility from mice in the other four treatments. Those females that were housed with males from weaning or treated with male urine also had smaller total numbers of litters, fewer total young, and smaller average litter sizes than did females for which the age of mating was delayed, by grouping or treatment with urine from grouped females, or by being held until age 68 days before mating. Control females mated at first oestrus generally were intermediate or did not differ from the male treatments on these dependent variables. There were no differences in the average number of female young/litter across the 6 treatments. However, females that were delayed in age of first mating had significantly more male young/litter than did females that were accelerated in their sexual development or control females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Social influences on reproductive development and fertility in female Djungarian hamsters (Phodopus campbelli).

Social influences on the sexual maturation of female Djungarian hamsters were investigated in two experiments. In the first experiment females were housed from weaning with an adult male, by themselves, or with a weanling sister. Maturation was accelerated in females housed with males as indicated by younger age at first ovulation, increased rates of ovarian and uterine growth, and lower LH levels at some ages. Maturation was delayed in females housed with sisters compared to those housed alone as measured by time of first ovulation and by lower estradiol levels at some ages. The most marked differences between groups occurred 8 to 12 days after weaning, suggesting that events during this period are particularly important in the social mediation of sexual maturation. In the second experiment the effects of reproductive suppression (caused by living with a sister) on the subsequent fertility of females housed with males were examined. If male-female pairs were housed in clean cages, no effects were observed; however, pairs housed in cages previously soiled by the female and her sister had fewer young surviving until 1 week of age despite no differences in the age of pregnancy onset or in the initial litter size. Thus, even cues present in unrenewed soiled bedding may have subtle but long lasting effects on reproductive function.     

Male influence on oestrous cycles in female woolly opossum (Caluromys philander)

Plasma progesterone concentrations and the occurrence of oestrous cycles were studied in isolated woolly opossums subsequently subjected to male influences during a 40-day period. Pairing (N = 48) or exposure to male urine (N = 15) resulted in all females exhibiting oestrous during the stimulation phase, providing evidence that the activation of ovarian activity in the woolly opossum involves pheromonal cues from males. The latency of occurrence of oestrous in stimulated females depended upon their sexual state before male stimulation. In anoestrous females, the mean latency was 20.7 +/- 0.9 days (N = 35), a value which agrees with the duration of the follicular phase. In females which first entered oestrous before male stimulation, the latency of induced oestrous was inversely correlated to the date of occurrence of the previous oestrous. The inter-oestrous interval was normal (38.1 +/- 1 days, N = 5) when females were in oestrous at the beginning of male stimulation. In contrast, the inter-oestrous interval was significantly shortened (28.7 +/- 2 days, N = 7) or lengthened (51.1 +/- 1.7 days, N = 16) depending on whether females were in the luteal or follicular phases at the beginning of male stimulation. During pairing several females became pregnant and gave birth 24 +/- 0.9 days (N = 13) after copulation. In the woolly opossum, the response to male influences involves mechanisms similar to those observed in eutherians and results in enhancement and synchronization of oestrous cycles in females. Pheromonal interactions could play an important role in synchronizing oestrous cycles in wild females during the dry season, a period when animals regroup to feed on spatially localized food resources.     

Oestrous cycle disruption in group-housed mice: evaluation of the involvement of tactile and pheromonal stimuli.

The role of tactile stimuli and pheromonal stimuli in the induction of oestrous cycle irregularities in mice was evaluated. In contrast to an adult regularly cycling female (the test female) housed in contact with 6 adult females, a test female housed in contact with 6 impuberal females failed to show disruption of oestrous cycle. Likewise, a test female housed in contact with bedding soiled by 6 group-housed adult females failed to exhibit disruption of oestrous cycle. By contrast, a test female housed in contact with 6 impuberal females on bedding soiled by 6 adult group-housed females exhibited a significant increase in the incidence of prolonged cycles. However, a test female housed with 6 impuberal females without direct contact with the bedding soiled by adult group-housed females exhibited a significant decrease in the incidence of prolonged cycles. The results suggest that tactile stimuli and pheromonal stimuli (probably present in the excrete of adult females) act synergistically in inducing cycle disruption. The findings further indicate that the female-originating pheromone involved in oestrous cycle disruption is non-volatile (not air-borne) and that it acts through contact.     

Social environment and reproduction in female pouched mice, Saccostomus campestris

Pouched mice were kept under controlled conditions of illumination (10D:14L) and temperature (22 +/- 2 degrees C). Age at vaginal opening, first oestrus and first conception did not differ significantly between juvenile females raised singly, in single-sex groups of 5, or with an adult male. After the introduction of a male, sterile cycles and/or matings before first conception were experienced by all females whether they were raised singly or in single-sex groups. Of 10 females raised with a male, 4 conceived at their first mating. Onset of puberty in juvenile females raised with an adult female was delayed, while in juvenile females raised with their families (mother, father and litter mates) only vaginal opening was delayed. However, when raised in family groups without the father, vaginal opening as well as first oestrus were delayed. Grouping of females after weaning, with or without a male, did not change the oestrous cycle pattern. Females in these groups cycled independently of each other and the females grouped with a male also mated and conceived independently of each other. Pregnancy was blocked in 7 of 8 females when the stud male was removed and a strange male was introduced. In females exposed to a succession of males, pregnancy was blocked up to 4 times.     

Effect of position in the uterus on the fetal weight of the 21st day of pregnancy in the unilaterally ovariectomized rat

Effects of intrauterine position of the fetuses on the weight of fetal sac, fetus and placenta were investigated on the 21th day of unilaterally (right) ovariectomized pregnant Wistar strain rats. Results were obtained as follows. 1. Litter size was negatively correlated with the mean weights of fetal sac and fetus. 2. The mean weights of male fetal sac and fetus were heavier than those of female ones, while there was no difference in the weight of placenta between male and female. 3. The mean weights of male fetal sac and fetus positioning ovarian end (OV) were lighter than those of ones at the other positions. And the highest frequency of the lightest weight of live fetuses was demonstrated at OV position. 4. The mean weights of male fetal sac and fetus positioning between two males (2M) were heavier than those of ones positioning not next to male (0M). And the mean weight of 2M female fetal sac was heavier than those of 0M one. 5. The mean weights of fetal sac and fetus positioning next to resorbed fetus were heavier than those of ones positioning not next to resorbed fetus.     

Characteristics of the oestrous cycle and influence of social factors in grey short-tailed opossums (Monodelphis domestica)

Characteristics of the oestrous cycle of grey short-tailed opossums were studied by vaginal smears. The period of oestrus was identified by a sudden proliferation of epithelial cells which lasted about 6 days (range 3-12 days), followed by a leucocytic infiltration. Oestrous cycle length showed a bimodal distribution of 14.4 days (5 cycles, range 11-17 days) and 32.3 days (10 cycles, range 28-39 days). Females housed with males showed more days of epithelial cell proliferation than did females housed alone, and oestrous periods tended to occur in synchrony, suggesting that social factors may influence the oestrous cycle in this species.     

The effects of oestrous condition and familiarity on the sexual behaviour of polecats (Mustela putorius and M. fur × M. putorius hybrids)

The effects of two factors on the sexual behaviour of polecats ( Mustela furo and M. putorius × M. furo hybrids) were investigated, in an indoor arena of 16 m², firstly the oestrous condition of the female and secondly the familiarity of the two individuals.
The initial approaches of a male polecat are similar irrespective of the oestrous condition of the female but his subsequent behaviour is dependent upon the female's response. Whereas males copulated with oestrous females they showed a wider repertoire of social acts and a greater number of changes of behaviour towards females which were not in oestrous. Unreceptive females elicited both sexual and aggressive behaviour from males.
Unfamiliar females provide a more powerful eliciting stimulus for the male's copulatory behaviour than do familiar females.     

Mating induces puberty in the female musk shrew.

Female musk shrews (Suncus murinus), lacking a behavioral estrous cycle, engage in copulatory behavior whenever tested; even during pregnancy, sexual activity can be displayed. Studies suggest that protracted sexual behavior has a functional significance in this species. Virgin females receiving a series of ejaculations over the course of several days are more likely to ovulate and subsequently deliver than animals given the same number of ejaculations over an interval of a few hours. After the virgin mating only one third of the ovaries placed in culture exhibit increased steroidogenesis. In the present set of studies, the hypothesis that the virgin mating induces the onset of puberty, in a manner similar to that in which male-related pheromones induce estrous in rodents, was tested. On the basis of gestational lengths it is evident that females mated three times (on Days 0, 4, and 8) became pregnant in the vast majority of cases as a result of the second and third matings. When the first and second matings were separated by 25 days, 82% of females ovulated in response to the second mating; less than one third of females mated only once ovulated. Finally females were housed across a screen from males, exposed to male urine, or housed alone prior to the virgin mating. In none of these cases did pre-exposure to male-related cues increase ovulation rates in response to the virgin mating. The results show that the virgin mating primes the neuroendocrine system in such a way that the pubertal ovulation can occur in response to subsequent mating.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of intrauterine and cervical manipulation on the equine oestrous cycle and hormone profiles.

Endometrial biopsy or endometrial biopsy and uterine culture taken on Day 4 after oestrus induced lysis of the corpus luteum (CL), resulting in a sharp decline in serum progesterone concentration and shortened the interoestrous interval in 8/12 and 32/33 oestrous cycles, respectively, during 2 experiments. Cervical dilatation 4 days after oestrus shortened the interoestrus interval in 5/10 and 0/5 oestrous cycles. Endometrial biopsy and culture on Days 1 and 3 after oestrus also induced CL lysis during 4 of 7 cycles. Total oestrogen (oestrone plus oestradiol) concentrations increased at the onset of the subsequent oestrus in mares biopsied on Day 4 of dioestrus or in control cycle oestrous periods. Endometrial biopsy also induced lysis of the CL in mares with persistent luteal function. It is postulated that intracervical or intrauterine manipulations during the luteal phase of the oestrous cycle may directly, or indirectly, stimulate the release of an endogenous luteolysin (prostaglandin) resulting in CL regression, followed by oestrus and ovulation in the mare.     

The oestrous cycle of the brown lemur, Lemur fulvus.

Examination of vaginal smears and observations of the colour and tumescence of the genitalia and discharge of mucus of 9 brown lemurs indicated that the oestrous cycle lasted for 30 days and that cycles occurred between September and July. The timing of cycles of females housed in visual isolation differed from that of females able to see other lemurs, indicating that the oestrous cycle in this species can be influenced by different housing conditions.     

Delay of sexual maturation in female house mice by exposure to grouped females or urine from grouped females

The experiments examined the timing, duration and possible enhancement effects of group contact on the delay of sexual maturation produced in prepubertal female house mice by urine from grouped females. One or three days of pheromone stimulation at specified ages during the first 2 weeks after weaning was not sufficient to delay puberty in females caged singly. However, pheromone treatment for 7 days, beginning during the first week after weaning, did significantly delay the onset of first vaginal oestrus relative to control females treated with water. Both the timing and duration of pheromone stimulation appear to be critical factors affecting pheromone-induced delay of sexual maturation. Mean ages at first oestrus for females housed with a group of 7 other females, for 3 or 7 days at specified ages during the first 2 weeks after weaning, did not differ from mean ages recorded with urine stimulation only. Contact with other females does not appear to alter or enhance the delay-of-maturation effect achieved with urine stimulation. In all these respects the maturation-delay pheromone of grouped female mice appears to differ from the puberty-accelerating pheromone of male mice.     

Presence of mother and unfamiliar female alters levels of testosterone,progesterone, cortisol,adrenocorticotropin, and behavior in maturing Guinea pigs

Although the guinea pig is characterized by precocial physical development and minimal active maternal care, studies suggest the presence of the mother can influence neuroendocrine and behavioral activity of offspring even well beyond weaning. Previous results may have been influenced by the procedure of housing weaned subjects with the mother to within 2 days of testing. The present study examined approximately 40-day-old guinea pigs housed apart from the mother for 0 (not rehoused), 2, or 10 days. Rehousing without the mother led to elevations in plasma testosterone (measured in males), progesterone (measured in females), cortisol, and adrenocorticotropin (ACTH) (both measured in males and females). Offspring housed without the mother for 10 days had the highest progesterone, cortisol, and ACTH levels. Testosterone elevations were observed in 2-day-, but not 10-day-, rehoused animals. Regardless of rehousing condition, 60 min isolation in a novel test cage elevated progesterone, cortisol, and ACTH, and reduced testosterone. These effects were all moderated if the subject was tested with the mother or another female. Sexual behavior toward the mother was observed frequently, but only in males housed apart from her prior to testing. Overall, males and females that had been housed apart from the mother interacted with her as they would an unfamiliar female. Our results corroborate previous findings, suggest the effect of housing apart from the mother on male testosterone is transitory, and indicate that continuous housing with the mother past weaning suppresses circulating progesterone in females and cortisol and ACTH in both sexes.     

The effect of pregnant and oestrous females on male testosterone and behaviour in the tammar wallaby

Tammar wallaby females (Macropus eugenii) are seasonally breeding marsupials with a post-partum oestrus after a highly synchronised birth period when testosterone concentrations rise in males. Chemical communication appears to be important for mating, as males show checking behaviour, sniffing the urogenital opening (UGO) and the pouch of females. This study investigates whether the presence of pregnant and oestrous females directly influences testosterone in males and if oestrous odours or secretion from the pouch or UGO are attractive. Concentrations of plasma testosterone were measured in males housed with pregnant and oestrous females during two consecutive cycles in the breeding season, and an artificially induced cycle in the non-breeding season. Males were also tested for their interest in swabs taken from the urogenital opening (UGO) or pouch of oestrous females. Testosterone increased sharply in males in the presence of pregnant and oestrous females during all cycles in both seasons, but there was no change when males were exposed to non-cycling females in lactational or seasonal diapause. Males had no preference for either oestrous or non-oestrous samples taken from the pouch or from the UGO from oestrous females. This study confirms that the increase in plasma testosterone in tammar males can be induced through the presence of pregnant and oestrous females, regardless of season and that the increase began when the females were in late-pregnancy. This confirms that the male's reproductive state is dependent on a signal from females and is not blocked through seasonal effects.     

Oestrous state dynamics in chemical communication by captive female Asian elephants

In many mammals, reproductive status is revealed through chemical cues in urine. The reproductive status of receivers may influence their interest in such signals. For social mammals that live in matrilineal groups, females may benefit by detecting the reproductive condition of herdmates. Responses to urine during oestrous cycles of senders and receivers are potential indicators of signal functions. We examined the chemosensory responses, first by four captive female Asian elephants,Elephas maximus , over their oestrous cycles to familiar follicular and luteal phase urine and second by 14 different female Asian elephants to unfamiliar conspecific follicular and luteal phase urine. We asked whether females could distinguish the reproductive state of another female as measured by their differential response to luteal- and follicular-phase urine. We further examined the influence of the receiver's reproductive status on response levels. Females responded more with specific tactolfactory trunk behaviours to follicular- than to luteal-phase urine, but only when the receiving female was in her follicular phase. Like their male conspecifics, Asian elephant females can detect changes in the reproductive state of conspecifics. The functional significance of this ability has yet to be determined but may be related more to the resource holding power of females in follicular phase than to a means for females to synchronize oestrous cycles. Such female-female communication may have important effects on social group dynamics. Copyright 2003 Published by Elsevier Science Ltd on behalf of The Association for the Study of Animal Behaviour.      

Mate Choice for Non-siblings in Wild House Mice: Evidence from a Choice Test and a Reproductive Test

Two experiments were designed to test whether wild house mice discriminate between olfactory cues from different kin and, if so, whether given preferences would relate to actual reproductive decisions. Experimental animals were mice born to the offspring of wild-caught house mice. Litter-mates stayed together until 60 d of age and were then housed individually. In a choice test, animals were placed in the middle of an arena with 4 openings which led to small cages containing bedding material from opposite-sex animals of known kinship (full-sib, cousin, unrelated) or clean material. Test animals (11 oestrous females, 11 males tested with oestrous females' bedding, 8 males tested with material from non-oestrous females) preferred conspecific to control bedding. Males tested with oestrous females' bedding significantly preferred unrelated to full-sib odours. In a second experiment, 34 males were each mated simultaneously to 3 females (sister, cousin, unrelated) and these groups were then housed together for 5, 10, and 15 d. Females were checked for litters during the next 20 d. Reproductive rate increased significantly in the 15 d cohabitation group, and significantly more cousin and unrelated females than sisters gave birth to a litter.     

Changes in episodic luteinizing hormone secretion leading to puberty in the lamb

In this study, we monitored episodic luteinizing hormone (LH) secretion throughout development in eight April-born ewe lambs to determine if a change in LH pulse patterns preceded first ovulation at puberty. LH pulses were measured in samples collected every 12 min for 6 h once in July, twice a month from 22 August to 2 October, and then weekly until puberty. Progesterone concentrations, measured in samples taken 3/wk, were used as an index of first ovulation, which occurred at 29.3 +/- 0.7 wk of age. LH pulse frequencies throughout most of this period ranged from 0 to 2 pulses/6 h, with no change over time. However, during the week prior to the first progesterone rise, there was a significant increase in pulse frequency to a level seen during the follicular phase in post-pubertal lambs. This increase in pulse frequency was evident in 7 of 8 lambs; pulses were not analyzed in the last lamb because samples were taken during the LH surge. In contrast, LH pulse amplitude did not increase prior to puberty. In fact, pulse amplitude declined linearly during the 3 wk before first ovulation and then increased during the follicular phase in post-pubertal animals. These results support the hypothesis that an increase in the frequency of episodic LH secretion is a key event leading to the onset of ovarian cycles in the lamb. Whether an increase in pulse amplitude is also necessary remains unclear. If so, it must occur just before the LH surge, since it was not detected in any samples taken before puberty in this study.     

Influence of pre- and post-copulatory pair contact on pregnancy success in Djungarian hamsters, Phodopus campbelli

Females housed with their mates for 3 or 4 days before mating took place (i.e. early in the oestrous cycle at the time of introduction to the mate) were significantly more likely to litter than were females housed with their mates for only 1 or 2 days before mating. The duration of post-copulatory pair contact had a complex effect on pregnancy success. While only 41% of females littered when they had 24 h of post-copulatory pair contact, females exposed to either longer or shorter durations of post-copulatory pair contact littered at significantly higher rates. Exposure to a strange male 24-48 h after mating did not produce a strange-male induced pregnancy block. The critical parameter responsible for the decrease in the number of females littering was the absence of the mate, irrespective of the presence or absence of a strange male. If this pattern of pregnancy block is adaptive for females, it seems probable that females in the wild require substantial levels of paternal investment by their mates.