Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats.
Prenatal maternal stress in rats and mice can demasculinize and feminize the sexual behavior of adult male offspring. Causal mechanisms are unknown, but one attractive hypothesis is that stress activation of maternal adrenal glucocorticoid secretion is the responsible agent. To test this hypothesis, pregnant rats were exposed to a variety of substances which enhance glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams and a positive stress control group (restraint under bright lights three times daily). All treatments reduced maternal weight gain, DEX most potently. No treatment altered litter size, stillbirths, or sex ratio, but DEX reduced weight at birth, an effect still seen at postnatal day 85. DEX, CORT, and stress reduced male adrenal weight at birth, while DEX and CORT altered sexual differentiation as measured by anogenital distance. Stress impaired adult male sexual performance but not the lordosis quotient following exposure of animals to stud males. DEX affected both measures. No other treatment had any significant effect on sexual behavior. No treatment altered plasma LH levels, either basal or in response to an estrogen challenge in adult gonadectomized males. In adulthood there was no treatment effect on stress reactivity, measured behaviorally or by plasma glucocorticoids. Correlational analysis revealed that weight gain during pregnancy was the single best predictor of subsequent sexual performance. It is concluded that prenatal dexamethasone exposure demasculinizes and feminizes male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)
Holson
R R
RR
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Gough
B
B
Sullivan
P
P
Badger
T
T
Sheehan
D M
DM
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000633:toxicity*; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000523:psychology*
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003345:Corticosterone