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Cited by 45Hypothalamic control of reproductive hormonesInflammatory Bowel DiseaseSperm and Testicular Function

Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

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Deboer, Mark D, Li, Yongli·2011·Pediatric Research
DOI 10.1203/pdr.0b013e3181ffee6cPMC PMC3039692
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Abstract

In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

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  • California mice have a slower pace of development compared to other rodents.

    “California mice are an ideal species for studying sex differences in stress responses (44) and have a slower pace of development compared to other rodents (45, 46).”

    From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [46]

    The Materials and Methods section identifies the study animals as C57BL6 mice, and the Abstract addresses delayed puberty following induced colitis. A search for California mice and comparative developmental pace found no passage in our copy addressing that claim. (LLM, conf=0.76)

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  1. [1]Ballinger AB Savage MO Sanderson IR Delayed puberty associated with inflammatory bowel disease Pediatr Res 2003 53 205 210 12538776
  2. [2]Brain CE Savage MO Growth and puberty in chronic inflammatory bowel disease Baillieres Clin Gastroenterol 1994 8 83 100 8003745
  3. [3]Paganelli M Albanese C Borrelli O Civitelli F Canitano N Viola F Passariello R Cucchiara S Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease Inflamm Bowel Dis 2007 13 416 423 17206686
  4. [4]DeBoer MD Barnes BH The importance of treatment regimens and pubertal status for growth in IBD J Pediatr 2009 154 936 937 19446107
  5. [5]Bousvaros A Sylvester F Kugathasan S Szigethy E Fiocchi C Colletti R Otley A Amre D Ferry G Czinn SJ Splawski JB Oliva-Hemker M Hyams JS Faubion WA Kirschner BS Dubinsky MC Challenges in pediatric inflammatory bowel disease Inflamm Bowel Dis 2006 12 885 913 16954808
  6. [6]Ahima RS Prabakaran D Mantzoros C Qu D Lowell B Maratos-Flier E Flier JS Role of leptin in the neuroendocrine response to fasting Nature 1996 382 250 252 8717038
  7. [7]Smith JT Acohido BV Clifton DK Steiner RA KiSS-1 neurones are direct targets for leptin in the ob/ob mouse J Neuroendocrinol 2006 18 298 303 16503925
  8. [8]Farooqi IS Leptin and the onset of puberty: insights from rodent and human genetics Semin Reprod Med 2002 20 139 144 12087499
  9. [10]Kaminski BA Palmert MR Genetic control of pubertal timing Curr Opin Pediatr 2008 20 458 464 18622205
  10. [11]Azooz OG Farthing MJ Savage MO Ballinger AB Delayed puberty and response to testosterone in a rat model of colitis Am J Physiol Regul Integr Comp Physiol 2001 281 R1483 R1491 11641119
  11. [12]DeBoer MD Li Y Cohn S Colitis causes delay in puberty in female mice out of proportion to changes in leptin and corticosterone J Gastroenterol 2010 45 277 284 20072791 PMC2850610
  12. [13]Adair LS Gordon-Larsen P Maturational timing and overweight prevalence in US adolescent girls Am J Public Health 2001 91 642 644 11291382 PMC1446647
  13. [14]Kaplowitz PB Link between body fat and the timing of puberty Pediatrics 2008 121 S208 S217 18245513
  14. [15]Lee JM Kaciroti N Appugliese D Corwyn RF Bradley RH Lumeng JC Body mass index and timing of pubertal initiation in boys Arch Pediatr Adolesc Med 2010 164 139 144 20124142 PMC4172573
  15. [16]Wirtz S Neufert C Weigmann B Neurath MF Chemically induced mouse models of intestinal inflammation Nat Protoc 2007 2 541 546 17406617
  16. [17]Kolho KL Huhtaniemi I Neonatal treatment of male rats with a gonadotropin-releasing hormone antagonist results in altered function of the pituitary-testicular axis in adult age Biol Reprod 1989 41 1084 1090 2696558
  17. [18]Korenbrot CC Huhtaniemi IT Weiner RI Preputial separation as an external sign of pubertal development in the male rat Biol Reprod 1977 17 298 303 889997
  18. [19]Marini M Bamias G Rivera-Nieves J Moskaluk CA Hoang SB Ross WG Pizarro TT Cominelli F TNF-alpha neutralization ameliorates the severity of murine Crohn's-like ileitis by abrogation of intestinal epithelial cell apoptosis Proc Natl Acad Sci U S A 2003 100 8366 8371 12832622 PMC166235
  19. [20]Bland JM Altman DG The logrank test BMJ 2004 328 1073 15117797 PMC403858
  20. [21]Simon D Puberty in chronically diseased patients Horm Res 2002 57 53 56 12065928
  21. [22]Wong SC Macrae VE McGrogan P Ahmed SF The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation J Pediatr Gastroenterol Nutr 2006 43 144 155 16877976
  22. [23]Feagins LA Kane SV Sexual and reproductive issues for men with inflammatory bowel disease Am J Gastroenterol 2009 104 768 773 19223893
  23. [24]Ito H Takazoe M Fukuda Y Hibi T Kusugami K Andoh A Matsumoto T Yamamura T Azuma J Nishimoto N Yoshizaki K Shimoyama T Kishimoto T A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease Gastroenterology 2004 126 989 996 15057738
  24. [25]Yamamoto M Yoshizaki K Kishimoto T Ito H IL-6 is required for the development of Th1 cell-mediated murine colitis J Immunol 2000 164 4878 4882 10779797
  25. [26]Sawczenko A Azooz O Paraszczuk J Idestrom M Croft NM Savage MO Ballinger AB Sanderson IR Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the −174 IL-6 G/C polymorphism in children Proc Natl Acad Sci U S A 2005 102 13260 13265 16150725 PMC1198995
  26. [27]Uno JK Kolek OI Hines ER Xu H Timmermann BN Kiela PR Ghishan FK The role of tumor necrosis factor alpha in down-regulation of osteoblast Phex gene expression in experimental murine colitis Gastroenterology 2006 131 497 509 16890604
  27. [28]Froicu M Cantorna MT Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury BMC Immunol 2007 8 5 17397543 PMC1852118
  28. [29]Bento AF Leite DF Claudino RF Hara DB Leal PC Calixto JB The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice J Leukoc Biol 2008 84 1213 1221 18653784
  29. [30]Walters TD Gilman AR Griffiths AM Linear growth improves during infliximab therapy in children with chronically active severe Crohn's disease Inflamm Bowel Dis 2007 13 424 430 17206672
  30. [31]Kalra PS Fuentes M Sahu A Kalra SP Endogenous opioid peptides mediate the interleukin-1-induced inhibition of the release of luteinizing hormone (LH)-releasing hormone and LH Endocrinology 1990 127 2381 2386 2226323
  31. [32]Rivier C Vale W Cytokines act within the brain to inhibit luteinizing hormone secretion and ovulation in the rat Endocrinology 1990 127 849 856 2115435
  32. [33]Nappi RE Rivest S Effect of immune and metabolic challenges on the luteinizing hormone-releasing hormone neuronal system in cycling female rats: an evaluation at the transcriptional level Endocrinology 1997 138 1374 1384 9075691
  33. [34]Huang BM Leu SF Yang HY Norman RL Testosterone effects on luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the mouse J Androl 2001 22 507 513 11330652
  34. [35]Sairam MR Krishnamurthy H The role of follicle-stimulating hormone in spermatogenesis: lessons from knockout animal models Arch Med Res 2001 32 601 608 11750736

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Authors
Deboer, M. D., & Li, Y.
Affiliations
University of Virginia (US)
ORCID
Deboer, Mark D
Venue
Pediatric Research
Publisher
Springer Science and Business Media LLC
Published
2011-01
Volume
69
Issue
1
Pages
34-39
ISSN
  • 0031-3998 (ISSN-L)
  • 1530-0447
DOI
10.1203/pdr.0b013e3181ffee6c
PMC
PMC3039692
OpenAlex
W2028766716
Cited by
45
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 8 · 2021: 2 · 2020: 1 · 2019: 4 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 4
FWCI
4.19
Type
journal article
Language
en
Open access
Locations
  • Pediatric Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Virginia
  • Pediatric Endocrine Society
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD060739)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
delayed puberty, inflammatory bowel disease, DSS-induced colitis, leptin, dietary restriction, body weight, follicle-stimulating hormone, testicular volume, colonic inflammation, cytokines, male mice, pubertal timing
MeSH terms
Analysis of Variance, Animals, Body Weight, Colitis, Enzyme-Linked Immunosorbent Assay, Follicle Stimulating Hormone, Humans, Male, Mice, Inbred C57BL, Puberty, Delayed, Radioimmunoassay, Testis, Testosterone, Dextran Sulfate, Leptin, Mice

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