Permanent changes in the functional development of accessory sex organs and in fertility in male mice after neonatal exposure to cyproterone acetate

ABSTRACT Male mice were injected daily with cyproterone acetate for 10 consecutive days during one of the four following periods: 1–10 days, 11–20 days, 21–30 days or 31–40 days. At all stages studied cyproterone acetate caused a significant reduction in the relative weights of epididymis, vas deferens, preputial gland and seminal vesicle in males killed 24 h after the last injection; the androgen content (testosterone + dihydrotestosterone) of the accessory sex organs was also reduced but the differences were not always significant. Cyproterone acetate treatment from 1 to 10 days resulted in a definitive reduction in the relative weights of all accessory sex organs studied and when injected from 11 to 20 days in epididymis and vas deferens. When cyproterone acetate was injected after 20 days of age, the inhibition of sexual organ weights was reversible and at adulthood organs were normally developed. Cyproterone acetate treatment induced a high percentage of infertile males only when injected from 1 to 10 days. Spermatogenesis, androgen levels in plasma and accessory sex organs, and sexual behaviour were not affected in sterile males. These results suggest that the functional development of accessory sex organs can be permanently affected by short-term neonatal exposure to endogenous androgens. J. Endocr. (1985) 104, 113–120

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Sexual maturation in male mice treated with cyproterone acetate from birth to puberty

Journal of Endocrinology ◽

10.1677/joe.0.1020103 ◽

1984 ◽

Vol 102 (1) ◽

pp. 103-107 ◽

Cited By ~ 7

Author(s):

Ch. Jean-Faucher ◽

M. Berger ◽

M. De Turckheim ◽

G. Veyssiere ◽

Cl. Jean

Keyword(s):

Seminal Vesicle ◽

Sexual Maturation ◽

Cyproterone Acetate ◽

Vas Deferens ◽

Male Mice ◽

Preputial Gland ◽

Early Stages ◽

Full Development ◽

Accessory Sex Organs

ABSTRACT Cyproterone acetate was administered every 2 days from 1 to 39 days of age to male mice which were killed 24 h or 20 days after the last injection. Cyproterone acetate caused a significant reduction in the relative weights of the epididymis, vas deferens, seminal vesicle and preputial gland, which was still evident at 60 days after birth. Testicular and epididymal androgens (testosterone and dihydrotestosterone) and circulating LH and FSH concentrations were equal to or higher than those of controls at 60 days. Cyproterone acetate did not inhibit spermatogenesis but all males were infertile. The results suggest that the peripheral effects of testosterone are necessary, during early stages of sexual maturation, in order to obtain subsequent full development of the accessory sex organs. J. Endocr. (1984) 102, 103–107

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Evidence for reversible and irreversible biochemical defects in accessory sex organs and kidney of neonatally androgenized male mice

Acta Endocrinologica ◽

10.1530/acta.0.1210121 ◽

1989 ◽

Vol 121 (1) ◽

pp. 121-128 ◽

Cited By ~ 3

Author(s):

G. Veyssiere ◽

Ch. Jean-Faucher ◽

M. Berger ◽

Cl. Jean

Keyword(s):

Protein Content ◽

Seminal Vesicle ◽

Vas Deferens ◽

Polyacrylamide Gel Electrophoresis ◽

Seminal Vesicles ◽

Protein Profiles ◽

Adult Mice ◽

Accessory Sex Organs ◽

Neonatal Administration ◽

Androgen Levels

Abstract. Studies were conducted to evaluate the effects of neonatal administration of supraphysiological doses of testosterone on the growth, hormone responsiveness, DNA and protein content, and protein profiles of the epididymis, vas deferens and seminal vesicles in adult mice. Results indicate that in androgenized males, testicular growth (DNA and protein content), circulating and organ androgen levels, and fertility were significantly depressed. The weights of the epididymis, vas deferens, seminal vesicle and kidney, but not that of the spleen, were significantly diminished subsequently to a reduction of protein (all organs) and DNA (epididymis, vas deferens) content. The efficacy of testosterone in promoting accessory sex organs and kidney growth, in adult castrated males, was persistently reduced in neonatally androgenized males. When assessed by DNA content, the response of all organs (except the seminal vesicle) was similar to that of controls, but it was significantly reduced from 16 to 43% when measured in terms of protein content. The protein profiles from seminal vesicles and vas deferens analysed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations which could be reversed by adult androgen therapy.

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CONCENTRATIONS OF LUTEINIZING HORMONE IN THE SERUM OF MALE MICE AFTER SHORT-TERM AGGRESSIVE INTERACTION

Journal of Endocrinology ◽

10.1677/joe.0.0850299 ◽

1980 ◽

Vol 85 (2) ◽

pp. 299-305 ◽

Cited By ~ 5

Author(s):

M. S. BARKLEY

Keyword(s):

Luteinizing Hormone ◽

Adult Male ◽

Sesame Oil ◽

Aggressive Interaction ◽

Male Mice ◽

Gonadal Function ◽

Short Term ◽

Organ Weights ◽

Gonadotrophin Secretion ◽

Strange Male

Adult male mice were castrated and implanted with silicone elastomer capsules containing either testosterone or sesame oil. Brief exposure to a strange male opponent depressed levels of LH in castrated animals treated with oil, but did not add to the suppressive effects of testosterone on the concentration of LH in serum. Accessory organ weights were not affected by brief aggressive encounters, nor were levels of testosterone in serum altered in response to repeated encounters with a submissive (olfactory bulbectomized) male opponent. The observation that exposure to a strange male conspecific suppressed secretion of gonadotrophin in the absence of gonadal androgen(s) suggests that stress-responsive, antigonadotrophic factors can inhibit pituitary-gonadal function. A mechanism whereby gonadotrophin secretion may be suppressed in the androgen-deprived state is discussed.

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Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens

Journal of Endocrinology ◽

10.1677/joe.0.1150241 ◽

1987 ◽

Vol 115 (2) ◽

pp. 241-246 ◽

Cited By ~ 18

Author(s):

Ch. Jean-Faucher ◽

M. Berger ◽

Ch. Gallon ◽

M. de Turckheim ◽

G. Veyssière ◽

...

Keyword(s):

Adult Male ◽

Cyproterone Acetate ◽

Growth Response ◽

Male Mice ◽

Renal Growth ◽

Kidney Size ◽

Female Mice ◽

Cellular Hypertrophy ◽

Renal Size ◽

Androgen Levels

ABSTRACT Kidneys of adult male mice are larger than those of females because of both cellular hyperplasia and hypertrophy. Administration of testosterone to adult female mice induced cellular hypertrophy but not hyperplasia, so that the weight of the kidney remained smaller than in male mice. The sexual dimorphism in kidney size is not congenital but programmed by neonatal endogenous androgens and expressed between 30 and 40 days of age. Treatment of newborn males with cyproterone acetate and of newborn females with testosterone induced female and male patterns of renal growth respectively. It appears that neonatal endogenous androgens are required to induce the characteristic cellular hyperplasia of the kidneys of male mice. Manipulation of androgen levels during neonatal and prepubertal life was found to affect the growth response of the kidney to androgens in adult male and female mice. J. Endocr. (1987) 115, 241–246

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Short-term exposure and long-term consequences of neonatal exposure to Δ9-tetrahydrocannabinol (THC) and ibuprofen in mice

Behavioural Brain Research ◽

10.1016/j.bbr.2016.04.001 ◽

2016 ◽

Vol 307 ◽

pp. 137-144 ◽

Cited By ~ 18

Author(s):

Gaëtan Philippot ◽

Fred Nyberg ◽

Torsten Gordh ◽

Anders Fredriksson ◽

Henrik Viberg

Keyword(s):

Neonatal Exposure ◽

Short Term ◽

Short Term Exposure ◽

Long Term Consequences

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Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-induced Weight Gain in Male Mice

10.1101/2020.12.04.412460 ◽

2020 ◽

Author(s):

E. Matthew Morris ◽

Roberto D. Noland ◽

Michael E. Ponte ◽

Michelle L. Montonye ◽

Julie A. Christianson ◽

...

Keyword(s):

Fatty Acid ◽

Weight Gain ◽

Energy Metabolism ◽

Energy Balance ◽

Fatty Acid Oxidation ◽

Positive Energy ◽

Acid Oxidation ◽

Male Mice ◽

Short Term

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.

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