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Intermedin attenuates LPS-induced inflammation in the rat testis.

Li L, Ma P, Liu Y, Huang C, O WS, Tang F, Zhang JV - PLoS ONE (2013)

Bottom Line: In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2).The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture.Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Gene and Cell Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen City, China.

ABSTRACT
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

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Histological examination of the rat testes and epididymis after LPS treatment or LPS and IMD cotreatment compared with saline control.(A) LPS-treated testes 6 h after injection, showing accumulation of immature germ cells (indicated by arrows) in the seminiferous tubule lumen, which was not observed in the IMD-cotreated testis. (B) LPS-treated testes 72 h after injection, showing increased inter cellular gaps (indicated by arrows) due to disruption of cell-cell contract and/or loss of cells in the seminiferous epithelium, which was not observed in the IMD-cotreated testis. (C) LPS-treated epididymis 72 h after injection, showing large numbers of round immature germ cells (indicated by arrowheads) in the epididymal lumen, which was not observed in the IMD-cotreated epididymis. (D) Quantitive presentation of the detached round immature germ cells in the epididymal lumen by counting five random fields under 20X magnification. Data were expressed as mean ± SEM; * P<0.05 by Student t-test for (D); For (A), (B), and (C), representative sections of n = 5–7 rats with similar results.
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pone-0065278-g004: Histological examination of the rat testes and epididymis after LPS treatment or LPS and IMD cotreatment compared with saline control.(A) LPS-treated testes 6 h after injection, showing accumulation of immature germ cells (indicated by arrows) in the seminiferous tubule lumen, which was not observed in the IMD-cotreated testis. (B) LPS-treated testes 72 h after injection, showing increased inter cellular gaps (indicated by arrows) due to disruption of cell-cell contract and/or loss of cells in the seminiferous epithelium, which was not observed in the IMD-cotreated testis. (C) LPS-treated epididymis 72 h after injection, showing large numbers of round immature germ cells (indicated by arrowheads) in the epididymal lumen, which was not observed in the IMD-cotreated epididymis. (D) Quantitive presentation of the detached round immature germ cells in the epididymal lumen by counting five random fields under 20X magnification. Data were expressed as mean ± SEM; * P<0.05 by Student t-test for (D); For (A), (B), and (C), representative sections of n = 5–7 rats with similar results.

Mentions: Histological examination of the testes and epididymis sections revealed the disruptive effects of LPS on testicular morphology. Compared with saline control, LPS-treated testes at 6 h after injection showed an accumulation of immature germ cells in the lumen (lumina) of some seminiferous tubules. Such an accumulation was not observed in the IMD-cotreated testes (FIG.4A). LPS-treated testes 72 h after injection showed an increase in inter-cellular gaps, due to the disruption of cell-cell contact or loss of cells in the seminiferous epithelium (FIG.4B), accompanied by large numbers of round, immature germ cells in the epididymal lumen (FIG.4C); this was not found with the IMD cotreatment (FIG.4B&C). Counting five random fields under 20X magnification showed a significant increase in the number of sloughing immature germ cells in LPS-treated epididymis compared with saline control, and this increase was eliminated with IMD cotreatment (FIG.4D).


Intermedin attenuates LPS-induced inflammation in the rat testis.

Li L, Ma P, Liu Y, Huang C, O WS, Tang F, Zhang JV - PLoS ONE (2013)

Histological examination of the rat testes and epididymis after LPS treatment or LPS and IMD cotreatment compared with saline control.(A) LPS-treated testes 6 h after injection, showing accumulation of immature germ cells (indicated by arrows) in the seminiferous tubule lumen, which was not observed in the IMD-cotreated testis. (B) LPS-treated testes 72 h after injection, showing increased inter cellular gaps (indicated by arrows) due to disruption of cell-cell contract and/or loss of cells in the seminiferous epithelium, which was not observed in the IMD-cotreated testis. (C) LPS-treated epididymis 72 h after injection, showing large numbers of round immature germ cells (indicated by arrowheads) in the epididymal lumen, which was not observed in the IMD-cotreated epididymis. (D) Quantitive presentation of the detached round immature germ cells in the epididymal lumen by counting five random fields under 20X magnification. Data were expressed as mean ± SEM; * P<0.05 by Student t-test for (D); For (A), (B), and (C), representative sections of n = 5–7 rats with similar results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672160&req=5

pone-0065278-g004: Histological examination of the rat testes and epididymis after LPS treatment or LPS and IMD cotreatment compared with saline control.(A) LPS-treated testes 6 h after injection, showing accumulation of immature germ cells (indicated by arrows) in the seminiferous tubule lumen, which was not observed in the IMD-cotreated testis. (B) LPS-treated testes 72 h after injection, showing increased inter cellular gaps (indicated by arrows) due to disruption of cell-cell contract and/or loss of cells in the seminiferous epithelium, which was not observed in the IMD-cotreated testis. (C) LPS-treated epididymis 72 h after injection, showing large numbers of round immature germ cells (indicated by arrowheads) in the epididymal lumen, which was not observed in the IMD-cotreated epididymis. (D) Quantitive presentation of the detached round immature germ cells in the epididymal lumen by counting five random fields under 20X magnification. Data were expressed as mean ± SEM; * P<0.05 by Student t-test for (D); For (A), (B), and (C), representative sections of n = 5–7 rats with similar results.
Mentions: Histological examination of the testes and epididymis sections revealed the disruptive effects of LPS on testicular morphology. Compared with saline control, LPS-treated testes at 6 h after injection showed an accumulation of immature germ cells in the lumen (lumina) of some seminiferous tubules. Such an accumulation was not observed in the IMD-cotreated testes (FIG.4A). LPS-treated testes 72 h after injection showed an increase in inter-cellular gaps, due to the disruption of cell-cell contact or loss of cells in the seminiferous epithelium (FIG.4B), accompanied by large numbers of round, immature germ cells in the epididymal lumen (FIG.4C); this was not found with the IMD cotreatment (FIG.4B&C). Counting five random fields under 20X magnification showed a significant increase in the number of sloughing immature germ cells in LPS-treated epididymis compared with saline control, and this increase was eliminated with IMD cotreatment (FIG.4D).

Bottom Line: In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2).The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture.Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Gene and Cell Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen City, China.

ABSTRACT
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

Show MeSH
Related in: MedlinePlus