Effects Of Intrauterine Position Research Articles

Effects of intrauterine position during gestation on specific endocrine and behavioral parameters that impact reproduction in domestic rabbits

Prior studies from others, performed in a different breed, reported that doe rabbits developing between two male siblings (2 M) during gestation display characteristics indicative of masculinization: larger anogenital distance (AGD), larger submandibular glands, and higher chinning frequency than females with zero (0 M) or one (1 M) contiguous brothers. Similar effects are provoked by injecting androgens to the pregnant doe suggesting that prenatal androgen exposure masculinizes female embryos. To further understand the scope of such masculinization we compared 0 M, 1 M, and 2 M females regarding behavioral, neuroendocrine, and somatic parameters, related or not to reproduction. IUP did not impact: body weight, sexual receptivity, mating-induced LH secretion, maternal nest-building, litter size, or milk output. At puberty: a) chinning frequency was: 0 M and males>1 M and 2 M; b) ambulation in open field was lowest in 1 M females and males. IUP effects on AGD were significant only on postnatal day 1: 0 M, 1 M, and males>2 M, in contrast to earlier study. Willingness to nurse at delivery was less frequent in 2 M than in 1 M and 0 M does and correlated with nursing occurrence across lactation. Does that did not nurse at parturition delivered fewer kits/min than those that nursed then, regardless of IUP. The duration of nursing bouts across lactation was significantly longer in the1 M and 2 M does that showed this behavior on postpartum days 1–20. Our findings indicate that IUP is associated with alterations in specific aspects of postpartum maternal behavior.

TRIENNIAL REPRODUCTION SYMPOSIUM: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A.

During critical periods in fetal life, there is an increased vulnerability to perturbations in endocrine function due to environmental factors. Small shifts in concentrations of hormones that regulate the differentiation of organs, such as estradiol and testosterone, can have permanent effects on morphology, enzymatic activity, and hormone receptors in tissues as well as neurobehavioral effects. These changes can lead to effects throughout life, including impacting the risk for various diseases (referred to as the Developmental Origins of Adult Health and Disease hypothesis). The intrauterine position phenomenon concerns the consequence for fetuses of randomly implanting next to embryos of the same or opposite sex. An intrauterine position next to males vs. females results in small differences in serum testosterone and estradiol during fetal life that are associated with marked effects on life history (such as lifetime fecundity) in both males and females born in litters (mice, rats, gerbils, rabbits, and swine) as well as human twins. Research with mice subsequently demonstrated that a very small experimental change in fetal serum estradiol levels altered organogenesis and caused permanent changes in organ function. Taken together, these findings led to the hypothesis that environmental chemicals that mimic or antagonize hormone action (e.g., endocrine disrupting chemicals) could also be causing harm at very low exposures (the "low dose" hypothesis) within the range of exposure of humans, domesticated animals, and wildlife. There is now extensive evidence from experimental laboratory animals, sheep, and humans that fetal exposure to very low (presumably safe) doses of the endocrine disrupting chemical bisphenol A (BPA), which exhibits estrogenic activity, can cause permanent changes that can increase the risk of a wide array of diseases. The reasons that federal regulatory agencies are ignoring the massive literature showing adverse effects of BPA and other endocrine disrupting chemicals are discussed.

Nurture: Effects of Intrauterine Position on Behaviour

Fetuses positioned next to littermates of the opposite sex may develop different sexually related traits and aggressive behaviour in later life. These effects of intrauterine position are due to hormonal transfer between fetuses. Testosterone from a male fetus that crosses the fetal membrane of an adjacent female fetus can affect molecular events in the female including modification of the steroid hormone receptors in hypothalamic neurons. The intrauterine environment may also account for the variability of laboratory animals and newborn human twins.

Testosterone treatment of pregnant rabbits affects sexual development of their daughters

The intrauterine position (IUP) may affect the sexual development of a female fetus in litter-bearing mammals. Females gestating between two males (2M) develop into masculinized adults compared to females without contiguous males (0M). Fetuses are known to secrete different types and amounts of steroid hormones during the prenatal period, and diffusing steroids may affect sexual differentiation of their neighbors, too. Exposure of elevated testosterone (T) levels generally results in masculinized anatomy and behavior in females of several rodent species. Our recent study showed that IUP-dependent masculinization is also present in the domestic rabbit, which shows large variation in sex related traits as adults. The aim of the present study was to test if the IUP effect in rabbits can be induced by exogenous testosterone treatment. By administering different doses of testosterone propionate (TP) to pregnant rabbits, and following anatomical and behavioral development of their female offspring, we obtained dose-dependent increase both in the anogenital distance (AGD) and chin-marking behavior of prenatal T exposed females. The effects of treatment corresponded to the variation due to intrauterine position in our previous study, namely, exposure to T of known external origin resulted in similar tendencies of masculinization in rabbit females as the in utero proximity to male siblings. Our results suggest that the IUP effects may have similar physiological bases across different mammalian taxa including Lagomorphs.

Digit Ratio (2D∶4D) Differences between 20 Strains of Inbred Mice

The second to fourth digit ratio (2D∶4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits. The story seems more complicated in laboratory mice. We have previously shown that there is no sex difference in the digit ratios of inbred mice, but found behavioral evidence to suggest that higher 2D∶4D is associated with more masculinized behaviors. Work examining intrauterine position effects show that neighbouring males raise pup digit ratio, suggesting again that higher digit ratios are associated with increased developmental androgens. Other work has suggested that masculinization is associated with lower digit ratios in lab mice. Here, we examine the fore- and hindlimb digit ratios of 20 inbred mouse strains. We find large inter-strain differences, but no sexual dimorphism. Digit ratios also did not correlate with mice behavioral traits. This result calls into question the use of this trait as a broadly applicable indicator for prenatal androgen exposure. We suggest that the inbred mice model presents an opportunity for researchers to investigate the genetic, and gene-environmental influence on the development of digit ratios.

Intrauterine Position Effects on Anogenital Distance and Digit Ratio in Male and Female Mice

Anogenital distance (AGD) and the ratio of the second (index) to fourth (ring) digit lengths (2D:4D) are two widely used indicators of prenatal androgen exposure. The former is commonly used in rodent models, while the latter is principally used in human studies. We investigated variation in these two traits in C57BL/6J mice to test the hypothesis that variation in these two traits reflect a common underlying variable, presumably testosterone exposure. AGD is a sexually dimorphic trait used to sex young rodents. This distance typically increases and becomes more male-like in female pups when their uterine neighbors are male. 2D:4D is sexually dimorphic in a number of species, including humans and other great apes. Lower digit ratios may be associated with greater exposure to androgens during fetal development in humans. We found the expected sexual dimorphism in AGD, but no significant sex difference in 2D:4D, and no correlation between 2D:4D and AGD. Gestating next to males increased a pup's 2D:4D ratio, but it had no effect on AGD. The lack of correlation between 2D:4D and AGDs in this mouse strain suggests that these two measures do not reflect a common influence of androgen exposure. The possible roles of temporal and localized effects of masculinization are discussed.

Measurement of the digit lengths and the anogenital distance in mice

In humans, research has demonstrated the ratio of the 2nd to 4th digit lengths (2D:4D) are: (i) sexually dimorphic with males having a lower ratio than females, the latter having near equidistant lengths [J. Manning, D. Scutt, J. Wilson, & D. Lewis-Jones, (1998). The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 13(11):3000–3004], and are theorized to be (ii) determined in utero during gestational development [J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 54(5):855–857], and (iii) correlated with prenatal androgen levels [J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: a new predictor of disease predisposition? Med Hypotheses. 54(5):855–857; J. Manning, R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of female beauty. Nature. 399:214–215; T. Williams, M. Pepitone, S. Christensen, B. Cooke, A. Huberman, N. Breedlove, et al., (2000). Finger-length ratios and sexual orientation: measuring people's finger patterns may reveal some surprising information. Nature. 404:455–456]. These phenotypes correspond to the hormonal effects of testosterone (i.e. androgens) in utero in both sexes. In mice, testosterone in utero is associated in males and females with the anogenital distance (AGD), a phenotype where AGD is greater in males and females contiguous with two males (2M) have a masculinized AGD phenotype whereas those juxtaposed to fewer males, one or zero (1M or 0M), have a more feminine phenotype, i.e. shorter AGD [F. vom Saal, & F. Bronson, (1980). Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development. Science. 208:597–599; R. Gandelman, F. vom Saal, & J. Reinisch, (1977). Contiguity to male foetuses affects morphology and behaviour of female mice. Nature. 266:722–724; A. Hotchkiss, & J. Vandenbergh, (2005). The anogenital distance index of mice ( Mus musculus domesticus): an analysis. Contem Top Lab Anim Sci. 44(4):46–48; C. Kinsley, J. Miele, C. Wagner, L. Ghiraldi, J. Broida, B. Svare, (1986). Prior intrauterine position influences body weight in male and female mice. Horm Behav. 20:201–211; S. Graham, R. Gandelman, (1986). The expression of ano-genital distance data in the mouse. Physiol Behav. 36(1):103–104; B. Ryan, & J. Vandenbergh, (2002). Intrauterine position effects. Neurosci Biobehav Rev. 26(6):665–678; J. Vandenbergh, & C. Huggett, (1995). The anogenital distance index, a predictor of the intrauterine position effects on reproduction in female house mice. Lab Anim Sci. 45(5):567–573]. Furthermore, in humans AGD is sexually dimorphic with neonate males having a greater distance than females [E. Salazar-Martinez, P. Romano-Riquer, E. Yanez-Marquez, M. Longnecker, M. Hernandez-Avila, (2004). Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environmental Health: A Global Access Science Source. 2004:3:(8) (doi:10.1186/1476-069X-3-8) [12]]. Recently, research has concluded that the digit lengths of mice have the same phenotypic pattern seen in humans, with the 2D:4D ratio being sexually dimorphic, i.e. lower in males and greater in females [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual dimorphism in digit-length ratios of laboratory mice. Anat Rec. 267(3):231–234; J. Manning, M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes. Med Hypotheses. 60(3):340–343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex difference in the digit length ratio in mice. Horm Behav. 39:325]. The following study was conducted to determine whether the digit length ratios in mice are correlated with a known in utero testosterone-dependent effect, the distance from the anus to the genital papilla, the AGD. The results of the experiment demonstrate that there is no correlation between AGD and the 2D:4D ratio in mice of either sex. Furthermore, no sexual dimorphism in the digit lengths was found as opposed to previous studies [W. Brown, C. Finn, & S. Breedlove, (2002). Sexual dimorphism in digit-length ratios of laboratory mice. Anat Rec. 267(3):231–234; J. Manning, M. Callow, & P. Bundred, (2003). Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes. Med Hypotheses. 60(3):340–343; W. Brown, C. Finn, & S. Breedlove, (2001). A sex difference in the digit length ratio in mice. Horm Behav. 39:325]. Although testosterone has been implicated in the digit length ratios, the present study would suggest that androgens do not have a causal relationship with testosterone-dependent phenotypes [J. Manning, D. Scutt, J. Wilson, & D. Lewis-Jones, (1998). The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 13(11):3000–3004; J. Manning, & P. Bundred, (2000). The ratio of 2nd to 4th digit length: A new predictor of disease predisposition?. Med Hypotheses. 54(5):855–857; J. Manning, R. Trivers, D. Singh, & R. Thornhill, (1999). The mystery of female beauty. Nature. 399:214–215]. The attribution of nature (i.e. genetic) and nurture (i.e. environment) in the development of life (i.e. resultant phenotype) is exceedingly complex and the correlation of one trait to another physical characteristic does not preclude there is a causal relationship.

Effect of intrauterine position on sex differences in the gabaergic system and behavior of rats

In multiparous species such as the rat (in this case the albino Wistar strain), steroid influence during fetal growth is affected by the relative intrauterine position of male and female fetuses and is stronger when the potential effects of contiguity and caudal position are combined. The effect of intrauterine position on gonadal steroid levels in neonatal and adult animals was examined using radioimmunoassay techniques. Since the organizing effect of prenatal steroids may influence the postnatal GABA content, HPLC was used to determine the gabaergic content in several hypothalamic and limbic areas in the adult rat. The effects of intrauterine position on adaptive behavior were examined by recording exploratory behavior (using the corridor and hole board tests) and intraspecific aggression (induced by isolation). Female pups influenced by males during development produced more testosterone. In adult males, those that developed closer to the cervix (and with no influence from other fetuses) produced more testosterone and less estradiol. The same animals also produced more hypothalamic GABA and showed greater exploratory capacity. No significant differences were seen between any experimental groups with respect to aggression. These results show increased variability between males with respect to adult exploratory behavior, and in the neurochemical and endocrine systems involved, due to intrauterine position during development. The effect of this physiological phenomenon on the structure of rodent populations is discussed.

Effects of intrauterine position on the behavior and genital morphology of litter‐bearing rodents

We review the literature describing hormonally mediated effects of intrauterine position on the genital morphology and reproductive behaviors of litter‐bearing rodents. We emphasize work carried out in our own laboratory in which male and female Mongolian gerbils served as subjects. The results of the studies we consider indicate that biologically significant aspects of the variance in morphology and reproductive strategy seen in all populations of adult rodents reflect variance in perinatal levels of exposure to gonadal hormones induced by intrauterine position. We conclude that studies of correlations between intrauterine position and adult characteristics provide opportunities to examine the impact of normal variation in perinatal exposure to hormones on adult mammalian phenotypes.

Effects of Intrauterine Position on the Metabolic Capacity of the Hypothalamus of Female Gerbils

Jones, D., F. Gonzalez-Lima, D. Crews, B. G. Galef, Jr. and M. M. Clark. Effects of intrauterine position on the metabolic capacity of the hypothalamus of female gerbils. Physiol Behav 61(4) 513–519, 1997.—The intrauterine position that a rodent fetus occupies relative to members of the same or opposite gender affects both its reproductive physiology and behavior when adult. Cytochrome oxidase histochemistry was used to assess regional differences in the oxidative metabolic capacity of the hypothalamus of female Mongolian gerbils that developed in utero between 2 female fetuses (n = 15) or between 2 male fetuses (n = 14). Cytochrome oxidase reactivity was measured densitometrically by experimenters unaware of subject intrauterine position. Gray-to-white matter ratios of optical density in 11 brain regions were used as a normalized index of metabolic capacity. Significant group differences in the metabolic capacity of the medial and the posterior parts of the anterior hypothalamus were revealed. Females that developed in utero between 2 male fetuses showed significant increases (19–22%) in cytochrome oxidase reactivity in these brain regions compared to that in females that developed between 2 female fetuses. The medial part of the anterior hypothalamus contributes to copulatory behavior, whereas the posterior part of the anterior hypothalamus may be involved in the control of pituitary gonadotropin secretion. Both these functions are influenced by intrauterine position during fetal life. To our knowledge, this is the first demonstration of metabolic changes in hypothalamic areas of the adult related to the differences in intrauterine position.

Urine marking and maternal aggression of wild female mice in relation to anogenital distance at birth

A series of experiments were conducted with wild house mice to verify the effect of intrauterine position on females' anogenital distance at birth (AGD) and to examine the relationships between a female's AGD, used as a bioassay of androgen exposure during fetal life, and her social behavior and reproductive success in adulthood. Experiment 1 showed that cesarean-delivered females that developed in utero between two males (2 M females) have significantly longer AGD's than females positioned between two females (0 M females). We then categorized naturally delivered females shortly after birth as having a long, medium or short AGD. In adulthood, these females were tested for their behavior towards unfamiliar pups, their rate of urine-marking in response to a variety of social stimuli, postpartum aggression and success in protecting their litters in response to male and female intruders. Adult females with different AGD's at birth did not differ either in their behavior toward pups or in their rate of urine marking. Conversely, males housed across a wire mesh partition from a long-AGD female deposited a higher number of urine marks than those exposed to a short-AGE) female. When tested after delivering a litter, long-AGD females displayed more tail-rattling (a component of agonistic behavior) towards intruders of both sexes in comparison to short-AGD females. These results are consistent with the hypothesis that females with a long AGE) are exposed to higher levels of Testosterone during fetal life than females with a short AGD. Although not related to AGD, other measures of maternal aggression were affected by postpartum day, sex of intruders and a female's infanticidal potential while a virgin.

Effect of intrauterine position on conceptus development, placental and endometrial release of progesterone and estrone in vitro, and concentration of steroid hormones in fetal fluids throughout gestation in swine

Twenty intact and 25 unilaterally hysterectomized-ovariectomized gilts were used to study the effect of fetal intrauterine position on conceptus development, concentrations of endogenous progesterone (P4) and estrone (E1) in the placenta and endometrium, and steroid hormone concentrations in amniotic and allantoic fluids during gestation. Gilts were hysterectomized at 40, 60, 80, or 100 d of gestation. Placental and endometrial tissues were pooled individually by the intrauterine position of the associated fetus and incubated separately, and concentrations of P4 and E1 in the medium were determined. Uterine status (intact or unilaterally hysterectomized-ovariectomized) did not affect any of the variables measured. Intrauterine position affected fetal and placental weights (P < 0.02 and 0.01, respectively) only at Day 40 of gestation. The weights of female fetuses bordered in utero by two males and their associated placentas were lower than those from other intrauterine positions. Intrauterine position had no effect on placental and endometrial P4 release or on E1, P4, and androgen concentrations in fetal fluids at any stage of gestation. At Day 100 of gestation, placentas associated with fetuses bordered by those of the same opposite sex (P < 0.01). This study indicates that intrauterine position in swine has a limited effect on conceptus development and on placental and endometrial steroidogenic activity.

Intrauterine position effects on sexually dimorphic asymmetries of Mongolian gerbils: Testosterone, eye opening, and paw preference

A series of experiments was undertaken to both discover and explore the causes of sexually dimorphic phenotypic asymmetries in infant and adult Mongolian gerbils. We found that (1) the order in which the eyes of individual gerbil pups opened varied with their gender; right eyes of female pups opened before left eyes, while left eyes of male pups opened before right eyes, and (2) the paw that adult gerbils held in the air while maintaining a species-typical tripedal stance varied with gender; female gerbils held their right paws in the air significantly more often than did male gerbils. Both order of eye opening and laterality of paw use while in a tripedal stance varied significantly as a function of the intrauterine position which subjects had occupied as fetuses. These data implicate exposure to testosterone as a mediator of the development of asymmetries exhibited by Mongolian gerbils.

Intrauterine position effects on steroid metabolism and steroid receptors of reproductive organs in male mice.

Mice differ in their adult reproductive characteristics as a function of whether they developed in utero between two male fetuses (2M males), which have higher testosterone levels, or between two female fetuses (0M males), which have higher estradiol levels. The present study was designed to further characterize biochemical parameters of 2M and 0M adult male mice. Activities of testicular steroidogenic enzymes, namely delta 5-3 beta-hydroxysteroid dehydrogenase/isomerase, 17 alpha-hydroxylase, and C17,20-lyase (C21SCC P450), were measured by means of radiometric assays and HPLC fractionation of substrate and products. Activity of 5 alpha-reductase in both seminal vesicle and prostate was measured by similar techniques. Estrogen and androgen receptor concentrations, which indicate capacity to respond to steroid hormones, were also examined in the accessory sex organs. For both seminal vesicle and prostate, 5 alpha-reductase activities were approximately 60% greater in 2M males than in 0M males, indicating greater capacity to form dihydrotestosterone from testosterone in organs from 2M mice. No significant differences were found in testicular steroidogenic enzymes between 2M and 0M animals, whereas the trend for all three activities was higher for 2M males than for 0M males. While no differences were found in estrogen receptor concentrations, 0M prostates had three times the concentration of androgen receptors (occupied receptors) compared to 2M prostates. Our findings suggest that intrauterine fetal position exerts a significant influence on subsequent adult androgen metabolism and androgen responsiveness in reproductive organs of adult male mice.

Blood flow in the uterine loop artery and loop vein is bidirectional in the mouse: Implications for transport of steroids between fetuses

In rodents, steroids are able to pass between fetuses. Although not previously examined in mice, we have provided evidence that blood flow in the uterine loop artery in rats is bidirectional and that steroids are transported between fetuses by diffusion via the uterine lumen, not via the uterine blood vessels of the mother. The direction of blood flow in the uterine loop artery and vein feeding each uterine horn in house mice was examined on day 17 of pregnancy. Dye was injected into the heart to determine the direction of blood flow in the uterine artery while injection of dye into individual placentae was used to determine the direction of blood flow in the uterine vein. Blood entered the loop artery from both the dorsal and caudal ends and was thus bidirectional. Venus blood flow from placentae was in a rostral direction from placentae in the rostral portion of a uterine horn and in a caudal direction from placentae in the caudal portion of a uterine horn. Comparison of anogenital distance and body weight at birth using a variety of classification schemes, based on different assumptions about the mechanism and direction of transport of steroids between fetuses, showed that the only scheme which accounted for variation in anogenital distance at birth in female mice was that which was based on the number of directly adjacent male siblings in utero. Taken together with recent findings in rats reported elsewhere, we conclude that blood flow in the uterine blood vessels is bidirectional, and steroids are transported between fetuses by diffusing through the amniotic fluid and across the fetal membranes of adjacent fetuses. We found that the common method of using the ratio of anogenital distance/body weight can lead to erroneous conclusions concerning intrauterine position effects on anogenital distance. Analysis of covariance tests whether variation in body weight contributes to differences in anogenital distance due to intrauterine position, and this method of analysis should be used in future studies.

The intrauterine position phenomenon and precopulatory behaviors of house mice

The effects of intrauterine position on two sexually dimorphic, precopulatory, reproductive behaviors, were investigated in male and female mice of three different genetic strains. The two behaviors were: (i) urinary odor preference and (ii) ultrasonic mating vocalizations. In addition, anogenital distance was measured both at birth and later in adulthood as a morphological index of masculinization. The intrauterine positions of individual mice relative to male and female siblings were classified according to two different classification schemes based upon hypotheses of interfetal steroid transfer: (i) the contiguity hypothesis which is based on diffusion of steroids within the uterus and (ii) the transvasculature hypothesis which posits the movement of fetal steroids via the maternal vasculature. In contrast to expectations, intrauterine position defined by either the contiguity hypothesis or the transvasculature hypothesis, did not have a consistent effect on urinary odor preferences, ultrasonic mating vocalizations, or anogenital distance in male and female house mice.

The effect of intrauterine position on the survival, reproduction and home range size of female house mice (Mus musculus)

In laboratory studies using albino house mice, a female's prior intrauterine position can affect many postnatal physiological, morphological and behavioral characteristics. Females flanked by males in utero (2M females) exhibit more aggressive dominance than females flanked by females (OM females). Thus, wild 2M females may be most successful during peak population densities when their aggressive nature would allow them to displace other females from limited resources. 2M and 0M females and males delivered by cesarean section were individually marked and released as young adults on two occasions onto a “highway island” (the area enclosed by exit and entrance ramps at an interchange) to determine whether 2 M females have a competitive advantage over 0 M females in the field. Males were included to create realistic population structure; their intrauterine position was not a treatment. Feeding stations afforded individuals an opportunity to exhibit their dominance by maintaining home-ranges at or near the stations. The populations were monitored by periodic live-trapping and reproductive success was determined using field body weights and by post-mortem examination for uterine implantation scars. Survival and capture rates were estimated, using a modified Jolly-Seber markrecapture program, for each of four intervals between trapping occasions over the course of 7 weeks. There were no overall differences in survivorship between 2M and 0M females, neither type of female was caught more frequently at feeding stations and they did not differ in measures of reproductive success. However, 2M females had significantly larger home-range sizes than 0M females and thus space use may be a trait “masculinized” by prior intrauterine position. Although there are a number of life-history characteristics that differ between 0M and 2M females in the laboratory that we did not test specifically in the field, our findings and other features of wild house mouse biology suggest that prior intrauterine position does not have a strong effect on survival and reproduction in the wild.

Stud males and dud males: intra-uterine position effects on the reproductive success of male gerbils

Sexually mature male Mongolian gerbils, Meriones unguiculatus, from known intra-uterine positions were each paired with a succession of nulliparous females. Those males that had matured in intra-uterine positions adjacent to two males (2M males) sired an average of 28% more young than did those males that had matured in intra-uterine positions between two females (2F males). In a second experiment, female gerbils chose between pairs consisting of one adult 2F male gerbil and one adult 2M male gerbil. When in induced oestrus (but not when in other hormonal states), the females spent significantly more time near 2M than near 2F males. Female gerbils in oestrus thus tended to affiliate with the more reproductively capable male in their vicinity.

The effects of intrauterine position on the degree of corpus callosum deficiency in two substrains of BALB/c mice

Measures of several intrauterine position variables as well as an index of abnormality of fetal commissure development (z score) were obtained for fetuses of two substrains of BALB mice, BALB/cWah1 and BALB/cWah2, known to differ as adults in the proportion of animals exhibiting deficient corpus callosum (about 55% & 20% respectively). The extent of midline commissure development at embryonic Day 17.5 for most strain 1 fetuses was significantly reduced compared to strain 2 fetuses of the same chronological age. The two substrains also differed with respect to mean litter size and mean body weight (strain 2 greater than strain 1 for both measures). The ovarian and cervical positions for strain 2 uteri were found to be the most favorable for body and placental growth; no such differences were evident in strain 1. In strain 2, fetuses in the left uterine horns showed lower z scores (more retardation) than littermates on the right side, but this difference was not evident in strain 1; no other right/left differences were found in strain 2 which could help to explain the right side advantage. None of the other position variables either separately or in combination was found to be important in predicting the z score index. Tests for randomness failed to provide evidence for nonrandom distribution of severely affected fetuses. We suggest that nongenetic variability resulting from stochastic events early in development and intrinsic to the fetus may be responsible for only certain BALB fetuses within a litter exhibiting the callosal anomaly.

Effect of intrauterine position and social density on age of first reproduction in wild-type female house mice (Mus musculus).

Effect of intrauterine position and social density on age of first reproduction in wild-type female house mice (Mus musculus).