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Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice.

Hirano T, Kobayashi Y, Omotehara T, Tatsumi A, Hashimoto R, Umemura Y, Nagahara D, Mantani Y, Yokoyama T, Kitagawa H, Hoshi N - J. Vet. Med. Sci. (2014)

Bottom Line: Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group.The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC.In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.

ABSTRACT
Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.

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Related in: MedlinePlus

Representative histology and immunohistochemistry of the testis in the control andstress group mice. (A) In the control group, normal cell arrangements were present inthe seminiferous tubules. (B) In the stress group, multinucleated giant cells(arrowhead) and vacuolization were occasionally found in the thinned seminiferousepithelia. Sperm were seen in the lumen of seminiferous tubules in both groups. HEstaining. (C) Immunoreactivity for single-stranded DNA was rarely detected in thenuclei of the spermatogonia of the control group testes. (D) Aggregations ofssDNA-positive spermatogonia and spermatocytes were observed in the stress grouptestes. Bar=200 µm (inset: 50 µm). (E) The number ofssDNA-positive cells significantly increased in the stress group compared to that ofthe control group. Values are presented as the mean ± SD (n=6 mice each).*P<0.05.
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fig_003: Representative histology and immunohistochemistry of the testis in the control andstress group mice. (A) In the control group, normal cell arrangements were present inthe seminiferous tubules. (B) In the stress group, multinucleated giant cells(arrowhead) and vacuolization were occasionally found in the thinned seminiferousepithelia. Sperm were seen in the lumen of seminiferous tubules in both groups. HEstaining. (C) Immunoreactivity for single-stranded DNA was rarely detected in thenuclei of the spermatogonia of the control group testes. (D) Aggregations ofssDNA-positive spermatogonia and spermatocytes were observed in the stress grouptestes. Bar=200 µm (inset: 50 µm). (E) The number ofssDNA-positive cells significantly increased in the stress group compared to that ofthe control group. Values are presented as the mean ± SD (n=6 mice each).*P<0.05.

Mentions: Histological and immunohistochemical findings of testis and brain: In thecontrol group, the testes showed normal cell arrangement and spermatogenesis in theseminiferous tubules (Fig. 3AFig. 3.


Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice.

Hirano T, Kobayashi Y, Omotehara T, Tatsumi A, Hashimoto R, Umemura Y, Nagahara D, Mantani Y, Yokoyama T, Kitagawa H, Hoshi N - J. Vet. Med. Sci. (2014)

Representative histology and immunohistochemistry of the testis in the control andstress group mice. (A) In the control group, normal cell arrangements were present inthe seminiferous tubules. (B) In the stress group, multinucleated giant cells(arrowhead) and vacuolization were occasionally found in the thinned seminiferousepithelia. Sperm were seen in the lumen of seminiferous tubules in both groups. HEstaining. (C) Immunoreactivity for single-stranded DNA was rarely detected in thenuclei of the spermatogonia of the control group testes. (D) Aggregations ofssDNA-positive spermatogonia and spermatocytes were observed in the stress grouptestes. Bar=200 µm (inset: 50 µm). (E) The number ofssDNA-positive cells significantly increased in the stress group compared to that ofthe control group. Values are presented as the mean ± SD (n=6 mice each).*P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197145&req=5

fig_003: Representative histology and immunohistochemistry of the testis in the control andstress group mice. (A) In the control group, normal cell arrangements were present inthe seminiferous tubules. (B) In the stress group, multinucleated giant cells(arrowhead) and vacuolization were occasionally found in the thinned seminiferousepithelia. Sperm were seen in the lumen of seminiferous tubules in both groups. HEstaining. (C) Immunoreactivity for single-stranded DNA was rarely detected in thenuclei of the spermatogonia of the control group testes. (D) Aggregations ofssDNA-positive spermatogonia and spermatocytes were observed in the stress grouptestes. Bar=200 µm (inset: 50 µm). (E) The number ofssDNA-positive cells significantly increased in the stress group compared to that ofthe control group. Values are presented as the mean ± SD (n=6 mice each).*P<0.05.
Mentions: Histological and immunohistochemical findings of testis and brain: In thecontrol group, the testes showed normal cell arrangement and spermatogenesis in theseminiferous tubules (Fig. 3AFig. 3.

Bottom Line: Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group.The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC.In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.

ABSTRACT
Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.

Show MeSH
Related in: MedlinePlus