Effects of Prenatal Testosterone on Sexual Behavior, Reproductive Morphology and LH Secretion in the Female Rat

Rhees, Reuben W.; Kirk, Blair A.; Sephton, Sandra E.; Lephart, Edwin D.

doi:10.1159/000111240

Cited by 100 publications

(61 citation statements)

References 17 publications

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“…Cultures from animals on P5, P7, P9 and P12 were investigated; the cultures from animals aged 4P15 did not stabilize satisfactorily. These ages were chosen to clearly separate the developmental stages of sexual differentiation known to occur during critical periods with often-abrupt limits 42 . Cultures were prepared using the roller tube method 43 .…”

Section: Methodsmentioning

confidence: 99%

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

et al. 2014

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The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-a. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

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Section: Methodsmentioning

confidence: 99%

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

et al. 2014

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“…From these results, since any endocrine disrupting activity of lindane is clearly weak, adverse effects might not have been expected in this study. A large number of investigations have shown effects of endocrine disruptors detected by examining AGD, nipple development, sexual maturation, estrous cycle, spermatogenesis, and sex organ weights (Aoyama and Suzuki, 2003;You et al, 2002;Ashby et al, 1997;Sharpe et al, 1995;Newbold et al, 1983;Yamasaki et al, 2005;Chamness et al, 1979;Clevenger et al, 1998;Gray et al, 1993Gray et al, , 1994Goldman et al, 1976;Rhees et al, 1997). Therefore, further studies using other chemicals, which have more definite endocrine disrupting activity, are considered necessary to establish the validity of the new protocol.…”

Section: Assessment Of the Test Methodsmentioning

confidence: 99%

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

et al. 2005

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-A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases in T3 and/or T4 in both sexes and generations at 300 ppm were presumed to be secondary changes associated with the induction of hepatic drug-metabolizing enzymes. Blood hormone analysis revealed no changes in sex hormones attributable to lindane in males or females. Hepatic drug-metabolizing enzyme activities were increased dose-dependently from 10 ppm in both sexes and generations, with the rise in BROD activity being the most prominent. There were also increases in MROD, EROD, T-6β-OH, and T4-UDP-GT activities (BROD >> EROD > MROD, T-6β-OH, T4-UDP-GT). This suggests that while lindane most strongly induces CYP2B, it also upregulates a number of other drug metabolizing enzymes, such as CYP1A, CYP3A, and UDP-GT. As for effects on reproductive function, lack of maternal behavior, including lactation and retrieval behavior, and consequent total litter loss were observed in F1 dams at 300 ppm. There were no effects of lindane on the estrous cycle, spermatogenesis, mating, fertility, pregnancy, or parturition. Neonatal toxicity was observed in bot...

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“…Individuals are particularly sensitive to organizational effects of certain hormones during critical developmental periods. Whereas perinatal exposure to androgens is essential for masculinization of males, numerous studies have shown that females exposed to androgens during the appropriate perinatal period can be masculinized in morphology, physiology, and behavior (Huffman and Hendricks 1981;Rhees et al 1997;Thornton and Goy 1986;vom Saal 1979).…”

Section: Role Of Androgens In Reproductive and Behavioral Developmentmentioning

confidence: 99%

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

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Ostby

VanDenburgh

et al. 2002

Environ Health Perspect

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In mammals, exposure to androgens early in development is essential for masculinization of the male reproductive phenotype. Male fetuses exposed to antiandrogens during perinatal life are permanently demasculinized in their morphology and physiology, whereas exposure to exogenous androgens permanently masculinizes females. In some litter-bearing species, proximity in utero of females to males can partially masculinize female siblings and alter their responsiveness to endocrine-disrupting compounds. However, in our strain of rat (CD-SD Charles River), intrauterine position does not significantly influence testosterone concentrations and anogenital distance of fetuses. In comparison, administration of testosterone propionate to pregnant females, at doses that doubled fetal female testosterone levels, did masculinize the reproductive system. Discovery of androgen-active chemicals in the environment has placed increased emphasis on describing the reproductive and behavioral effects of both natural and environmental androgens and antiandrogens. Recently, the effects of an antiandrogen, vinclozolin, on the brain and behavior were cited as a special concern by the U.S. Environmental Protection Agency in its risk assessment of this pesticide. In rats, one such behavior that is perinatally organized by androgens is social play. Males play more than females, and administration of exogenous androgens during the neonatal period alters the juvenile expression of this sexually dimorphic behavior. Vinclozolin is an androgen receptor antagonist that inhibits androgen-dependent tissue growth in vivo. We were interested in whether developmental exposure to vinclozolin could also alter androgen-dependent behaviors such as play. Neonatal male rats were injected on postnatal days (PNDs) 2 and 3 with corn oil, the pharmacologic antiandrogen flutamide (50 mg/kg), or vinclozolin (200 mg/kg). On PNDs 36-37 animals were observed for social play. Behaviors associated with general social activity such as sniffing and dorsal contact were unaffected by treatment. However, play behavior in males treated with flutamide or vinclozolin was significantly reduced, resembling levels of play characteristic of females rather than untreated males. Therefore, this study demonstrates that perinatal exposure to vinclozolin, an environmental antiandrogen, can alter androgen-dependent play behavior in the male rat.

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Effects of Prenatal Testosterone on Sexual Behavior, Reproductive Morphology and LH Secretion in the Female Rat

Cited by 100 publications

References 17 publications

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

Evaluation of a Two-Generation Reproduction Toxicity Study Adding Endopoints to Detect Endocrine Disrupting Activity Using Lindane

Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat.

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