Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat Part 2: Effects on reproductive parameters, on sex behavior, on memory retention and on hypothalamic expression of aromatase and 5alpha-reductases in the offspring.
The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted mixture of four indicator congeners (PCB 126, 138, 153 and 180) was injected subcutaneously to dams at the dose of 10 mg/kg daily from GD15 to GD19 and then twice a week till weanling. The results indicated that developmental PCB exposure produced important changes in the dimorphic hypothalamic expression of both aromatase and the 5alpha-Rs, which were still evident in adult animals. We observed that female puberty onset occurs earlier than in control animals without cycle irregularity, while testicular descent in males was delayed. A slight but significant impairment of sexual behavior and an important alteration in memory retention were also noted specifically in males. We conclude that PCBs might affect the dimorphic neuroendocrine control of reproductive system and of other neurobiological processes.
Colciago
A
A
Department of Endocrinology, Pathophysiology and Applied Biology, University of Milano, Italy.
Casati
L
L
Mornati
O
O
Vergoni
A V
AV
Santagostino
A
A
Celotti
F
F
Negri-Cesi
P
P
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D042944:Cholestenone 5 alpha-Reductase / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D052244:Endocrine Disruptors; D011078:Polychlorinated Biphenyls; D001141:Aromatase; D042944:Cholestenone 5 alpha-Reductase