Ingeborg L. Ward

Prenatal Stress Feminizes and Demasculinizes the Behavior of Males

Male rats were exposed to prenatal or postnatal stress, or both. The prenatally stressed males showed low levels of male copulatory behavior and high rates of female lordotic responding. Postnatal stress had no effect. The modifications are attributed to stress-mediated alterations in the ratio of adrenal to gonadal androgens during critical stages of sexual differentiation. Specifically, it appears that stress causes an increase in the weak adrenal androgen, androstenedione, from the maternal or fetal adrenal cortices, or from both, and a concurrent decrease in the potent gonadal androgen, testosterone.

Activation of lordotic responding in female rats by suppression of serotonergic activity.

After systemic administration of several serotonergic antagonists, female rats that had been ovariectomized, adrenalectomized, and estrogen-primed showed lordotic responding. Lordosis could also be elicited after direct placement of serotonergic receptor blockers into hypothalamic sites known to contain serotonergic terminals. None of the treatments activated the soliciting component of the estrous behavior pattern of the female rat. It is postulated that the hypothalamus contains serotonergic terminals which suppress lordotic responding.

The prenatal stress syndrome: Current status☆

Exposure of female rats to stressors during the last week of pregnancy results in a selective feminization and demasculinization of adult sexual behaviors in the male offspring. No behavioral abnormalities are detectable in the female offspring, and reproductive morphological structures appear normal in both sexes. Existing data suggest that the mechanism mediating the so called Prenatal Stress Syndrome in male rats is an alteration in fetal testicular enzyme activity. This, in turn, leads to abnormal levels of testosterone, the hormone believed to masculinize sexual behavior potentials at critical stages of perinatal development. Specifically, the activity of the steroidogenic enzyme delta 5-3 beta-hydroxysteroid dehydrogenase in fetal Leydig cells and plasma titers of testosterone are low in prenatally stressed males on days 18 and 19 of gestation, a time when both of these substances reach maximal levels in control males. The implications of this model for sexual behavior differentiation in higher organisms is explored.

Maternal Stress Decreases Steroid Aromatase Activity in Brains of Male and Female Rat Fetuses

Steroid aromatase activity was measured in homogenates of combined hypothalamic and amygdaloid specimens obtained from 17- to 21-day-old male and female rat fetuses. The fetuses were obtained both fro

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.

Fetal testosterone surge: Specific modulations induced in male rats by maternal stress and/or alcohol consumption

Plasma testosterone (T) was measured in control male and female rats on gestational days 16, 17, 18, 19, and 20 and on days 17-20 in males from dams who were fed ethanol and/or were stressed during pregnancy. Circulating T in control males showed an earlier rise, yielding a longer period of prenatal T elevation, than was reported previously (Endocrinology 106 (1980)306). Compared to control males, exposure to alcohol-alone augmented T on days 18 and 19, stress-alone attenuated prenatal T, and the combination of stress and alcohol completely blocked the normal rise in T between days 17 and 18. When these prenatal alterations in T are viewed along with effects these same treatments have on the postparturient T surge (Horm. Behav. 41 (2002) 229), a possible explanatory mechanism emerges for the uniquely different behavioral patterns of sexual behavior differentiation induced in males by prenatal exposure to alcohol, stress, or both factors. Whereas the potential for feminine behavior is retained to the extent that either the prenatal or the neonatal T surge is attenuated, the male potential is more sensitive to reductions in the fetal surge and is maximally disrupted if both the prenatal and the postparturitional T surges are suppressed.

Effects of prenatal stress on avoidance acquisition, open-field performance and lordotic behavior in male rats ☆

Abstract Prenatal stress enhanced lordotic behavior potentials in male rats but did not feminize patterns of active avoidance acquisition or open-field performance. These results suggest that prenatal stress selectively feminizes some but not all behavior patterns shown to differentiate under the influence of perinatal gonadal hormones. In the rat, the critical period for the differentiation of active avoidance behavior appears to span prenatal and early neonatal ontogeny.

Male and female sexual behavior potential of male rats prenatally exposed to the influence of alcohol, stress, or both factors

Adult sexual behaviors were characterized in male rats prenatally exposed to ethanol, stress, or ethanol combined with stress; 60% to 75% of each group exhibited female-typical lordosis. A substantial proportion of males subjected to alcohol (44%) or to alcohol with stress (54%) failed to ejaculate. The adult genitalia and testicular size appeared normal in all groups. Either alcohol or stress can suppress fetal plasma testosterone. Thus, exposing pregnant dams to alcohol, particularly in association with stress, may alter the hormonal milieu of their male fetuses sufficiently to block full masculinization and defeminization of sexually dimorphic copulatory behavior potentials, but not anatomy. It appears that certain pharmacological and stressful factors can interact during fetal ontogeny to influence the process of sexual behavior differentiation.

Naltrexone blocks the effects of prenatal stress on sexual behavior differentiation in male rats

The male offspring of rats stressed three times daily during days 14-21 of pregnancy were more likely to show lordotic behavior when tested in adulthood than were control males. This feminization of sexual behavior was not observed if the mothers were injected with the opioid antagonist naltrexone before being stressed. These data suggest that endogenous opioids released under conditions of stress can alter the normal process of sexual behavior differentiation in the fetal male rat.

Prenatal stress and prepuberal social rearing conditions interact to determine sexual behavior in male rats

The two major categories of factors known to influence adult sexual behavior potentials are the relative amounts of androgen present during specific stages of perinatal ontogeny and adequate social stimulation during prepuberal development. The possible interaction between these two was evaluated by characterizing the ejaculatory and lordotic behavior potentials of prenatally stressed and control male rats that had been weaned at 16 days of age and raised either in total social isolation or with a same-age female, a control male, or a prenatally stressed male. The decrement in male sexual behavior produced by prenatal stress was attenuated by raising the male with either a female or a control male. Social isolation alone or in combination with stress resulted in severely deficient male behavior. Peripheral skin shock promoted ejaculatory behavior in many previously noncopulating prenatally stressed males raised with other stressed males, but it was ineffective in most isolated animals. The high lordosis potential characteristic of prenatally stressed male rats was slightly lower in the group with a female cagemate and was markedly decreased by social isolation. These results support and extend the finding by Dunlap, Zadina, and Gougis (1978) that prenatal hormonal events and prepuberal rearing conditions can interact to attenuate or accentuate the effects that either treatment alone has on the development of adult sexual behavior potentials.