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PubMed2002

Prenatal diagnosis of female pseudohermaphroditism associated with bilateral luteoma of pregnancy: case report.

Female pseudohermaphroditism associated with luteoma of pregnancy (LP) is a rare condition characterized by varying degrees of masculinization of a female fetus. We describe a case, diagnosed at 13 weeks gestation. Transvaginal ultrasound at 5 weeks of gestation revealed a normal intrauterine gestational sac and an enlarged maternal right ovary. Re-examination at 13 weeks showed a fetus with male external genitalia. Cytogenetic investigation on amniotic fluid revealed a normal female karyotype 46,XX. Follow-up sonography confirmed the previous assignment of male external genitalia and a second amniocentesis was negative for the SRY gene. High levels of androgens were found in the maternal blood. A diagnosis of female pseudohermaphroditism associated with bilateral LP was made. A healthy girl was born by Caesarean section with complete masculinization of external genitalia (Prader V). Histology confirmed a bilateral LP. To the best of our knowledge this represents the first case of prenatal diagnosis of female pseudohermaphroditism associated with LP and demonstrates the feasibility of diagnosis by sonography from 13 weeks gestation. This is also the first case described of Prader V masculinization associated with LP.

Adult↗
PubMed2002

Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study.

Testosterone plays a major role in male sexual development. Exposure of females to testosterone in utero can induce masculine characteristics such as anovulation, increased anogenital distance (AGD), absence of nipples, retention of male-like tissues, and agenesis of the lower vagina. In addition, high levels of androgens during fetal development can lead to toxic effects such as reduced litter size and viability. The study of the effects of testosterone administration during sexual differentiation provides a foundation for understanding the effects of environmental androgens on fetuses, a sensitive subpopulation. In the current study, we investigated the ability of a range of concentrations of testosterone propionate (TP) administered prenatally to masculinize female and alter male offspring, and measured maternal and fetal T levels. Pregnant Sprague-Dawley rats were dosed by sc injection on gestational day (GD) 14-19 (GD 1= day of plug) with either corn oil (vehicle; 0.1 ml/rat) or with 0.1 ml of TP solution at 0.1, 0.5, 1, 2, 5, or 10 mg/0.1 ml. Parturition was delayed at 2, 5, and 10 mg TP, litter size was reduced at 5 and 10 mg TP, and pup weight was significantly reduced in both sexes at 0.5 mg TP and higher doses. Viability of offspring was unaffected at any dosage level. Androgenic effects seen at 0.5 mg TP in females included increased AGD at weaning and adulthood, reduced number of areolas and nipples, cleft phallus, small vaginal orifice, and presence of prostate tissue. This dose of TP elevated maternal T levels 10x but had no effect on fetal T levels. At 1 mg TP and above, female AGD on postnatal day (PND) 2 (or postcoital day 24 [gestation length = 22(1/2)]) was increased; areolas and nipples were virtually eliminated; levator ani muscle, bulbourethral glands, and seminal vesicles (2 mg TP and above) were present; none of the females developed a vaginal orifice and many females in the 1 and 2 mg TP dose groups developed a greatly distended, fluid-filled uterus after puberty. Maternal T levels at 1 mg TP were elevated 30x, and female fetal T levels showed an 80% increase. Male offspring displayed a reduced AGD and body weight on PND 2 at 0.5 mg TP and higher doses. These effects were not evident by weaning and male offspring displayed no malformations. We conclude that gestational administration of 0.5 and 1 mg TP masculinizes female offspring without greatly affecting pup viability or pregnancy of the dam. This study provides a useful model for in utero testing of environmental androgens for their potential to induce developmental abnormalities.

Abnormalities, Drug-Induced↗
PubMed2005

The ontogeny of the urogenital system of the spotted hyena (Crocuta crocuta Erxleben).

Studies were conducted to elucidate the importance of androgen-mediated induction of the extreme masculinization of the external genitalia in female spotted hyenas. Phallic size and shape; androgen receptor (AR) and alpha-actin expression; and sex-specific differences in phallic retractor musculature, erectile tissue, tunica albuginea, and urethra/urogenital sinus were examined in male and female fetuses from Day 30 of gestation to term. Similar outcomes were assessed in fetuses from dams treated with an AR blocker and a 5alpha-reductase inhibitor (antiandrogen treatment). Clitoral and penile development were already advanced at Day 30 of gestation and grossly indistinguishable between male and female fetuses throughout pregnancy. Sex-specific differences in internal phallic organization were evident at Gestational Day 45, coincident with AR expression and testicular differentiation. Antiandrogen treatment inhibited prostatic development in males and effectively feminized internal penile anatomy. We conclude that gross masculinization of phallic size and shape of male and female fetuses is androgen-independent, but that sexual dimorphism of internal phallic structure is dependent on fetal testicular androgens acting via AR in the relevant cells/tissues. Androgens secreted by the maternal ovaries and metabolized by the placenta do not appear to be involved in gross masculinization or in most of the sex differences in internal phallic structure.

Androgen Antagonists↗
PubMed1992

Role of prostaglandins in the testosterone-dependent wolffian duct differentiation of the fetal mouse.

Recent observations from this laboratory indicated a role of prostaglandin E2 (PGE2) in masculine differentiation of the external genitalia of the fetal mouse, induced by fetal testosterone. In this communication, we further investigated the role played by PGE2 in the testosterone-induced differentiation of the internal genital tract (Wolffian duct) of the fetal mouse. Using in vitro organ culture bioassay of Wolffian duct differentiation, we determined the effect of a PG-depleting agent, namely, anti-PGE2 antibody, and of inhibitors of PG synthesis for their ability to prevent Wolffian duct differentiation in the presence of testosterone. We demonstrated that anti-PGE2 antibody inhibited Wolffian duct differentiation in a dose-dependent manner in embryonic male explants containing fetal testes. At 1:10 dilution, the antibody inhibited the appearance of the entire Wolffian duct as well as growth of the specimen. At 1:100 dilution, however, only development of the Wolffian duct was prevented, as indicated by the absence of regions of the Wolffian duct or by the presence of epithelial disintegration throughout the ductal lumen. The antibody at 1:1000 dilution produced no significant effect on the appearance of the Wolffian duct. PGE2 (10 micrograms/ml) replacement in the medium prevented Wolffian duct disintegration induced by anti-PGE2. We next determined whether the testosterone-dependent Wolffian duct differentiation requires ongoing PG synthesis within the reproductive tract and analyzed the effects of the compounds inhibiting PG synthesis at the level of phospholipase A2 (PLA2) namely, cortisone and dexamethasone-and of those inhibiting at the level of cyclooxygenase-namely, aspirin and indomethacin. We have demonstrated that both PLA2 and cyclooxygenase inhibitors inhibited Wolffian duct differentiation in the male explant, i.e., in the presence of testis. These compounds also prevented the appearance of the Wolffian duct in female explants induced by exogenous testosterone. PGE2 added in the medium blocked the anti-masculinizing effects of PG synthesis inhibitors both in the male and female specimens. Thus, it appears that PG synthesis plays a role in the testosterone-induced masculine differentiation of the Wolffian duct.

Animals↗
PubMed1991

Gender-related behavior development in females exposed to diethylstilbestrol (DES) in utero: an attempted replication.

This report concerns the role of prenatal hormones in normal and abnormal psychosexual differentiation. Several studies indicate that perinatal treatment of infrahuman female mammals with diethylstilbestrol (DES) masculinizes certain features of their brain and behavior. Accordingly, the authors have hypothesized that prenatal exposure to DES may also masculinize the gender-role behavior of girls and women. A previous study suggested that prenatally DES-exposed women show decreased interest in parenting. The authors failed to replicate these findings in a different sample despite the use of similar methodology. Post-hoc analysis shows that the assessment devices would have detected masculinization if it were present. The implications of these findings for an understanding of psychosexual development are discussed.

Adolescent↗
PubMed2003

Hormonally active agents in the environment and children's behavior: assessing effects on children's gender-dimorphic outcomes.

BACKGROUND: Early sex hormone exposure contributes to gender-dimorphic behavioral development in mammals, including humans. Environmental toxicants concentrated in contaminated sport fish can interfere with the actions of sex steroids. METHODS: This study developed an outcome variable by combining gender-dimorphic behaviors that differentiates boys and girls. Offspring of participants in the New York State Angler Cohort Study (NYSACS) were targeted in a parent-report postal survey. Instruments were selected based on findings of gender differences in the general population. RESULTS: A linear discriminant function model incorporating three gender behavior scales correctly classified the sex of 97.7% of children (252 boys and 234 girls) from a random NYSACS sample. The discriminant function was cross-validated by correctly classifying the sex of 98.4% of children (457 boys and 425 girls) from the remaining NYSACS cases and 97.6% of children (154 boys and 142 girls) from an independent school sample. Within-sex stepwise multiple regression analyses revealed that masculine behavior increased among boys with age and with the number of years of maternal sport fish consumption. In girls, older age and previous live-born siblings were associated with more masculine behavior, whereas feminine behavior increased with the duration of breast feeding. These associations were replicated in an independent sample. CONCLUSIONS: A linear discriminant function effectively transformed the binary classification of sex (male-female) to a bipolar continuum of gender (masculinity-femininity). Findings from this study are consistent with the hypothesis that environmental contaminants contribute to shifts in gender-role behavior. Future investigations will need to account for competing explanations of this effect.

Adult↗
PubMed2004

The relationship between sexual dimorphism in human faces and fluctuating asymmetry.

Previous studies have found both support and lack of support for a positive relationship between masculinity and symmetry, two putative signs of mate quality, in male faces. We re-examined this relationship using an explicit measure of facial fluctuating asymmetry, as well as other measures of asymmetry, and measures of facial masculinity/femininity. We also used ratings of these traits for faces. Further, we examined the relationship between facial sexual dimorphism and body asymmetry. We found no significant correlations between facial masculinity and any of our measures of asymmetry or ratings of symmetry in males. Facial femininity was not consistently associated with facial symmetry in females, but was associated with body symmetry. Therefore, for females, but not males, facial femininity and body symmetry may reflect similar aspects of mate quality. We also examined the relationships between trait ratings and measurements. Our results provide validation of our ability to measure aspects of asymmetry that are perceived to be symmetrical, and aspects of sexual dimorphism that are perceived as feminine in females and masculine in males.

Adolescent↗
PubMed2004

Concordant preferences for opposite-sex signals? Human pheromones and facial characteristics.

We have investigated whether preferences for masculine and feminine characteristics are correlated across two modalities, olfaction and vision. In study 1, subjects rated the pleasantness of putative male (4,16-androstadien-3-one; 5alpha-androst-16-en-3-one) and female (1,3,5 (10),16-estratetraen-3-ol) pheromones, and chose the most attractive face shape from a masculine-feminine continuum for a long- and a short-term relationship. Study 2 replicated study 1 and further explored the effects of relationship context on pheromone ratings. For long-term relationships, women's preferences for masculine face shapes correlated with ratings of 4,16-androstadien-3-one and men's preferences for feminine face shapes correlated with ratings of 1,3,5(10),16-estratetraen-3-ol. These studies link sex-specific preferences for putative human sex pheromones and sexually dimorphic facial characteristics. Our findings suggest that putative sex pheromones and sexually dimorphic facial characteristics convey common information about the quality of potential mates.

Adolescent↗
PubMed2006

Facial and bodily correlates of family background.

It has been suggested that absence of the father during early childhood has long-reaching effects on reproductive strategy and development of offspring. This paper reports two studies designed to investigate the physical characteristics of daughters associated with father absence. Study 1 used a facial averaging method to produce composite images of faces of women whose parents separated during their childhood (who were 'father absent'), women whose parents remained together, but had poor quality relationships and women whose parents were together and had good quality relationships. Images were then rated by male and female judges. Father absence and poor parental relationships were associated with apparent facial masculinity and reduced attractiveness in daughters. Poor parental relationships were also associated with reduced apparent health. Study 2 compared family background with body measurements and found that father absence or a poor quality relationship between parents were associated with body masculinity (high waist-to-hip ratio) and increased weight-for-height and adiposity. These results highlight the possibility of physical masculinization being associated with purported father absence 'effects'.

Adolescent↗
PubMed2006

Reproductive strategy, sexual development and attraction to facial characteristics.

Sexual reproduction strategies vary both between and within species in the level of investment in offspring. Life-history theories suggest that the rate of sexual maturation is critically linked to reproductive strategy, with high investment being associated with few offspring and delayed maturation. For humans, age of puberty and age of first sex are two developmental milestones that have been associated with reproductive strategies. Stress during early development can retard or accelerate sexual maturation and reproduction. Early age of menarche is associated with absence of younger siblings, absence of a father figure during early life and increased weight. Father absence during early life is also associated with early marriage, pregnancy and divorce. Choice of partner characteristics is critical to successful implementation of sexual strategies. It has been suggested that sexually dimorphic traits (including those evident in the face) signal high-quality immune function and reproductive status. Masculinity in males has also been associated with low investment in mate and offspring. Thus, women's reproductive strategy should be matched to the probability of male investment, hence to male masculinity. Our review leads us to predict associations between the rate of sexual maturation and adult preferences for facial characteristics (enhanced sexual dimorphism and attractiveness). We find for men, engaging in sex at an early age is related to an increased preference for feminized female faces. Similarly, for women, the earlier the age of first sex the greater the preference for masculinity in opposite-sex faces. When we controlled sexual dimorphism in male faces, the speed of sexual development in women was not associated with differences in preference for male facial attractiveness. These developmental influences on partner choice were not mediated by self-rated attractiveness or parental relationships. We conclude that individuals assort in preferences based on the rapidity of their sexual development. Fast developing individuals prefer opposite-sex partners with an increased level of sexually dimorphic facial characteristics.

Adolescent↗
PubMed1999

Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3.

The tra-2 gene of the nematode Caenorhabditis elegans encodes a predicted membrane protein, TRA-2A, that promotes XX hermaphrodite development. Genetic analysis suggests that tra-2 is a negative regulator of three genes that are required for male development: fem-1, fem-2, and fem-3. We report that the carboxy-terminal region of TRA-2A interacts specifically with FEM-3 in the yeast two-hybrid system and in vitro. Consistent with the idea that FEM-3 is a target of negative regulation, we find that excess FEM-3 can overcome the feminizing effect of tra-2 and cause widespread masculinization of XX somatic tissues. In turn, we show that the masculinizing effects of excess FEM-3 can be suppressed by overproduction of the carboxy-terminal domain of TRA-2A. A FEM-3 fragment that retains TRA-2A-binding activity can masculinize fem-3(+) animals, but not fem-3 mutants, suggesting that it is possible to release and to activate endogenous FEM-3 by titrating TRA-2A. We propose that TRA-2A prevents male development by interacting directly with FEM-3 and that a balance between the opposing activities of TRA-2A and FEM-3 determines sex-specific cell fates in somatic tissues. When the balance favors FEM-3, it acts through or with the other FEM proteins to promote male cell fates.

Animals↗
PubMed2000

Androgyny and creativity: a study of the relationship between a balanced sex-role and creative functioning.

The relationship between creativity and androgyny was studied in 163 women and men with the Creative Functioning Test (CFT) and the Bem Sex Role Inventory (BSRI). A 2 (femininity: high/low) x 2 (masculinity: high/low) x 2 (sex) ANOVA was conducted on subjects' CFT scores. A significant interaction effect between femininity and masculinity was found showing that subjects high on both femininity and masculinity (androgynous) and low on both scales (undifferentiated) reached higher CFT scores than female-typed and male-typed subjects. Further, a significant three-way interaction including sex of subject indicated that the former two-way interaction was accounted for by men only.

Adult↗
PubMed1997

Self as the feminine principle.

In analytical psychology, ego is associated with consciousness and the masculine principle. Although the feminine principle generally characterizes the unconscious, it was not assigned a psychic structure equivalent to the ego. This paper proposes a model of the psyche where self and ego are the major modes of psychic experience. The self as the 'being' mode represents the feminine principle and functions according to primary process; the ego represents 'doing', the masculine principle and secondary process. Feminine and masculine principles are considered to be of equal significance in both men and women and are not limited to gender. Jung's concept of the self is related to the Hindu metaphysical concepts of Atman and Brahman, whose source was the older Aryan nature-oriented, pagan religion. The prominence of self in analytical psychology and its predominantly 'feminine' symbolism can be understood as Jung's reaction to the psychoanalytic emphasis on ego and to Freud's 'patriarchal' orientation. In Kabbalah, a similar development took place when the feminine principle of the Shekinah emerged in a central, redemptive role, as a mythic compensation to the overtly patriarchal Judaic religion. In the proposed model of the psyche neither ego nor self represents the psychic totality. The interplay of both psychic modes/principles constitutes the psyche and the individuation process.

Ego↗
PubMed1984

Abortion outcome as a function of sex-role identification.

The present study investigated the relationship between sex-role identification and abortion outcome in 120 women receiving 1st trimester abortions. The sex-role concept dimension was measured both ty self-attributions of sex-role traits (as measured by the Bem Sex-Role Inventory) and by lifestyle (career vs. homemaker) trait attbibutions. Psychological and physiological aspects of abortion outcome were included: slighlty more than 7% of scores were in the symptomatic range, similar to percentages found in previous studies. Both Androgyny (r = -.42, p.001) and Masculinity (r = -.23, p.05) were found to be related to positive abortion outcome. Androgyny was more strongly related, which suggests that a balance of masculine and feminine traits, at least for women in the post-abortion situation, is prefereable to high Masculinity scores alone. Congruence between one's self-image and one's image of a career woman was also found to be related to abortion outcome (r = .31, P.01). In attempting to differentiate between the upper and lower 10% of the distribution of abortion outcome, only 2 variables, Androgyny and self-career congruence, survived parameter criterion, and accounted for 32% of the variance.

Abortion, Induced↗
PubMed1998

The implications for academic attainment of perceived gender-appropriateness upon spatial task performance.

BACKGROUND: Male superiority in spatial ability has traditionally been used as an explanation for the male domination of 'spatial' disciplines such as mathematics, science and computing. Data are presented which show the degree of male domination of these disciplines at a range of academic levels. AIMS: To evaluate the effect of describing a spatial ability test either as a measure of spatial ability (traditional format) or as a measure of empathy, upon male and female performance. Psychological gender is also assessed to evaluate the role of masculinity and femininity upon performance. METHOD: Eighty-four sixth form students were presented with the Group Embedded Figures Test in the assessment's traditional format and as a measure of 'empathy'. Levels of masculinity and femininity were also assessed using the Bem Sex Role Inventory. RESULTS: Whilst the description of the nature of the assessment did not affect male performance, female performance' varied significantly as a function of test description. Females only underperformed when the test was described as a measure of spatial ability. Additionally, those high in masculinity were found to outperform those high in femininity. CONCLUSIONS: The results suggest that 'apparent' sex differences in spatial ability are more accurately described as psychological gender differences which determine the motivation to attempt the assessments. COMMENT: The implications for genderised activities (such as computing) within education are discussed.

Achievement↗
PubMed2002

Prevention of latently expressed CYP2C11, CYP3A2, and growth hormone defects in neonatally monosodium glutamate-treated male rats by the N-methyl-D-aspartate receptor antagonist dizocilpine maleate.

Neonatal administration of monosodium glutamate (MSG) can produce latently expressed defects in drug metabolism and growth hormone secretion as well as stunted growth and obesity. Instead of secreting growth hormone in the masculine episodic profile, plasma hormone levels are generally undetectable in affected adult male rats. Moreover, male-specific isoforms of cytochrome P450 (P450; e.g., CYP2C11 and CYP3A2), whose combined levels comprise the bulk of the total hepatic P450 in adult male rats, are similarly undetectable in these animals. Since "signaling elements" in the masculine episodic growth hormone profile are solely responsible for the elevated characteristic male-like expression levels of CYP2C11 and CYP3A2, suppression of the isoforms in the MSG-treated rats appeared to be caused by the simple absence of the hormone from the circulation. However, the reported failures of restored physiologic masculine growth hormone profiles to correct the P450 defects suggested the occurrence of direct MSG-induced liver damage independent of the well known hypothalamic lesions produced by the amino acid. Concurrent administration of dizocilpine maleate (MK-801), a selective and highly potent noncompetitive N-methyl-D-aspartate receptor antagonist of glutamate, completely prevented the adverse effects of neonatal MSG treatment on P450 expression, growth hormone secretion, and growth parameters, indicating that the amino acid-induced defects are solely a result of neuronal (i.e., hypothalamic) damage produced at the time of MSG exposure. The irreversibility of the P450 damage is described as resulting from secondary defects initially induced by the neuronal lesions.

Animals↗
PubMed1991

The effects of peripubertal testosterone on ethylmorphine demethylase activity in adult rats testectomized neonatally.

The physiologic activity of ethylmorphine demethylase (EMDM) is 2.5 times greater in adult male rats than in females. Defeminization, effected neonatally by testicular androgens, causes 65% of the increase while masculinization causes the rest. Castration of the intact adult does not alter the defeminized activity of the enzyme but abolishes its masculinized activity. Testosterone restores the latter. Adults that are not defeminized, because of neonatal castration, have enzymes unresponsive to testosterone. Thus, defeminization seems necessary for the expression of masculine activity. This was studied by castrating males at birth (day 1) and implanting capsules of testosterone propionate on day 35. On day 71, the activity had increased 4.4-fold to physiologic levels, compared with rats receiving no steroid (1.9 nmol.min-1.mg-1). Removal of the implant on day 71 decreased the activity on day 84 to that of the no-steroid rats. Thus, defeminization is neither caused by androgen in peripubertal rats nor needed to effect full physiologic activity of the enzyme. The activation of EMDM by peripubertal testosterone may reflect its regulation of growth hormone; first, testosterone (days 35-71) failed to increase enzyme activity in males hypophysectomized on day 35; second, growth hormone infused (5 micrograms.h-1) over days 71-76 blocked the activation, actually decreasing activity 3.7-fold; third, the activity induced by testosterone was further increased (26%) by growth hormone release-inhibiting hormone (5 micrograms.h-1, days 71-76).

Androgens↗
PubMed1999

The orthodox view of brain sexual differentiation.

The standard view of sexual differentiation of the brain, derived primarily from work with mammals, is that the same steroidal signal which permanently masculinizes the body early in life, androgen, also permanently masculinizes the nervous system. This oversimplified view overlooks the rich diversity of mechanisms produced by natural selection. We review the mechanisms underlying sexual differentiation of what may be the simplest mammalian model, the spinal nucleus of the bulbocavernosus (SNB), a system that is intimately associated with sexual differentiation of the periphery. Indeed, in many instances, early androgen can permanently masculinize the SNB system but, surprisingly, these early influences may depend to some extent on social mediating factors. Furthermore, in adulthood, androgen continues to affect the SNB system in diverse ways, acting on several different loci, indicating a life-long plasticity in even this simple system. Finally, there is evidence that adult androgens interact with social experience in order to affect the SNB system. Thus the SNB system displays a far richer array of interactions than the standard view of sexual differentiation would predict. Examination of other systems and other species, as depicted in the following reports, reveals a far more complicated, and far more interesting perspective on how the brains and behaviors of males and females diverge.

Amygdala↗