In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood.
When administered to postpubescent male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could impair sexual differentiation of the central nervous system (CNS) and thereby alter male reproductive function. To examine this possibility, sexually dimorphic functions were assessed in male rats born to dams given TCDD (0.064, 0.16, 0.40, and 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation. Masculine sexual behavior was assessed at approximately 60, 75, and 115 days of age. When TCDD-exposed males were caged with receptive control females their mount, intromission, and ejaculation latencies were far longer than normal; these effects were dose-related and were statistically significant at maternal doses as low as 0.16, 0.064, and 0.16 micrograms TCDD/kg, respectively. The numbers of mounts and intromissions to ejaculation were slightly increased by TCDD, while copulatory rates [(mounts+intromissions)/min] were significantly decreased at the three highest maternal doses. Except for a modest increase at the higher doses, TCDD had little effect on the postejaculatory interval. Following assessment of their masculine sexual behavior, the males were castrated and 6 weeks later tested for feminine sexual behavior (lordosis). After being primed with estradiol benzoate and treated with progesterone, males displayed dose-related increases in lordosis quotient and lordosis intensity in response to being mounted by another male. These effects were statistically significant at maternal doses as low as 0.16 and 0.40 micrograms TCDD/kg, respectively. To determine if perinatal TCDD exposure alters the sexually dimorphic regulation of luteinizing hormone (LH) secretion, the LH secretory responsiveness of the hypothalamic/pituitary axis to ovarian steroids was assessed. In unexposed, gonadectomized female rats primed with estradiol benzoate, progesterone injection produced a surge in plasma LH concentrations, whereas in similarly treated control males, plasma LH concentrations were unaffected by progesterone. In castrated, estradiol benzoate-primed male rats that were perinatally exposed to TCDD, progesterone treatment produced dose-related increases in plasma LH concentrations that were statistically significant at the two highest maternal doses. We conclude that in utero and lactational exposure to small amounts of TCDD demasculinizes and feminizes male rats. These effects cannot be accounted for by TCDD-induced hypophagia, modest reductions in adult plasma androgen concentrations, possible nonspecific changes in motor activity, or possible reductions in penile sensitivity to sexual stimulation. The altered sexual behaviors and LH secretion were observed when nearly all TCDD had been excreted (as evidenced by uninduced hepatic ethoxyresorufin-O-deethylase activity).(ABSTRACT TRUNCATED AT 400 WORDS)
Mably
T A
TA
School of Pharmacy, University of Wisconsin, Madison 53706.
Moore
R W
RW
Goy
R W
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Peterson
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RE
D000367:Age Factors; D000818:Animals; D001942:Breast Feeding; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005262:Feminization; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008141:Lordosis; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D009747:Nutritional Physiological Phenomena; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D012723:Sex; D012733:Sex Differentiation / Q000187:drug effects*; D013997:Time Factors
D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D011374:Progesterone; D007986:Luteinizing Hormone