Infertility caused by diabetes can be saved!

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia

In addition, more and more evidences show that diabetic hyperglycemia can extensively damage the male reproductive system, and is accompanied by severe testicular histological damage, including damage to the vas deferens and spermatogenesis, decreased serum sex hormones, oxidative stress and

At present, the screening of effective candidate drugs for traditional Chinese medicine has attracted more and more attention

At present, the screening of effective candidate drugs for traditional Chinese medicine has attracted more and more attention

In addition, Nan et al.

Recent studies have also shown that ICA also has anti-apoptotic effects in other systems

Therefore, it is reasonable to speculate that the mitochondrial apoptosis pathway may be involved in the protective effect of ICA on the male reproductive system

Therefore, it is reasonable to speculate that the mitochondrial apoptosis pathway may be involved in the protective effect of ICA on the male reproductive system

1.

1.

The serum levels of testosterone, LH, and FSH in the T2DM group were significantly lower than those in the control group; compared with the T2DM group, both the metformin and ICA medication groups recovered sex hormone levels (Figure 1)

2.

2.

In order to determine the protective effect of ICA on male reproductive function, we first measured testicular weight, epididymal weight, sperm count and sperm motility

Then further check the histological structure

3.
ICA up-regulates the expression of proliferating PCNA

3.
ICA up-regulates the expression of proliferating PCNA ICA up-regulates the expression of proliferating PCNA

In addition, we have also studied the distribution and expression of proliferating cell nuclear antigen (PCNA), which plays a vital role in the balance between cell survival and death
.
The results showed that PCNA staining can be detected in almost all spermatogenic cells and supporting cells.
The strongest area of ​​PCNA staining is in the perimeter area of ​​the seminiferous tubules, which are the spermatocytes, primary spermatocytes and supporting cells.
Main location (Figure 3A)
.
The number of PCNA-positive cells (Figure 3B) and PCNA mRNA expression (Figure 3C) in the T2DM group were significantly reduced and down-regulated, respectively
.
After ICA treatment, PCNA signal and PCNA positive cells increased significantly (Figure 3A and B)
.
Pcna mRNA expression was also significantly up-regulated (Figure 3C)
.
Compared with ICA, metformin treatment showed a similar effect (Figure 3)
.

In addition, we have also studied the distribution and expression of proliferating cell nuclear antigen (PCNA), which plays a vital role in the balance between cell survival and death
.
The results showed that PCNA staining can be detected in almost all spermatogenic cells and supporting cells.
The strongest area of ​​PCNA staining is in the perimeter area of ​​the seminiferous tubules, which are the spermatocytes, primary spermatocytes and supporting cells.
Main location (Figure 3A)
.
The number of PCNA-positive cells (Figure 3B) and PCNA mRNA expression (Figure 3C) in the T2DM group were significantly reduced and down-regulated, respectively
.
After ICA treatment, PCNA signal and PCNA positive cells increased significantly (Figure 3A and B)
.
Pcna mRNA expression was also significantly up-regulated (Figure 3C)
.
Compared with ICA, metformin treatment showed a similar effect (Figure 3)
.

In addition, the qPCR results showed that compared with the control group, the mRNA expression levels of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the type 2 diabetes group were significantly down-regulated , And both metformin and ICA treatment partially restored the mRNA expression levels of GPx and SOD in the testes of diabetic rats (Figure 4)
.

In addition, the qPCR results showed that compared with the control group, the mRNA expression levels of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the type 2 diabetes group were significantly down-regulated , And both metformin and ICA treatment partially restored the mRNA expression levels of GPx and SOD in the testes of diabetic rats (Figure 4)
.

4.
ICA activates SIRT1-HIF-1α axis

4.
ICA activates SIRT1-HIF-1α axis 4.
ICA activates SIRT1-HIF-1α axis

More and more studies have shown that one of the most studied acetylases, SIRT1, plays an important role in spermatogenesis and male reproductive function
.
There is a clear correlation between SIRT1 and insulin resistance
.
In addition, SIRT1 can directly deacetylate and stabilize HIF-1α.
HIF-1α is a hypoxia-activated transcription regulator that can regulate the transcription response of hypoxia response factors, thereby protecting spermatogonia in the testis from apoptosis
.
These studies suggest that the SIRT1-HIF-1α axis plays an important role in repairing DM-induced male reproductive dysfunction
.

More and more studies have shown that one of the most studied acetylases, SIRT1, plays an important role in spermatogenesis and male reproductive function
.
There is a clear correlation between SIRT1 and insulin resistance
.
In addition, SIRT1 can directly deacetylate and stabilize HIF-1α.
HIF-1α is a hypoxia-activated transcription regulator that can regulate the transcription response of hypoxia response factors, thereby protecting spermatogonia in the testis from apoptosis
.
These studies suggest that the SIRT1-HIF-1α axis plays an important role in repairing DM-induced male reproductive dysfunction
.

Therefore, this study further tested the activity of SIRT1-HIF-1α axis
.
In the T2DM group, the numbers of SIRT1-positive and HIF-1α-positive cells decreased (Figure 5A, C)
.
qRT-PCR and western blotting analysis showed that Sirt1 and Hif-1α were both down-regulated (Figure 5B, D and E)
.
In contrast, ICA or metformin can significantly reverse these conditions, not only enhancing the signal of SIRT1 and HIF-1α (Figure 5A and C), but also up-regulating the expression of SIRT1 and HIF-1α (Figure 5B, D and E)
.

Therefore, this study further tested the activity of SIRT1-HIF-1α axis
.
In the T2DM group, the numbers of SIRT1-positive and HIF-1α-positive cells decreased (Figure 5A, C)
.
qRT-PCR and western blotting analysis showed that Sirt1 and Hif-1α were both down-regulated (Figure 5B, D and E)
.
In contrast, ICA or metformin can significantly reverse these conditions, not only enhancing the signal of SIRT1 and HIF-1α (Figure 5A and C), but also up-regulating the expression of SIRT1 and HIF-1α (Figure 5B, D and E)
.

5.
ICA reduces mitochondrial apoptosis signals in diabetic rats

5.
ICA reduces mitochondrial apoptosis signal in diabetic rats 5.
ICA reduces mitochondrial apoptosis signal in diabetic rats

The normal development of germ cells and reproductive system is highly dependent on the regulation and balance of BCL-2 family proteins on mitochondrial apoptosis
.
Studies have confirmed that the anti-apoptotic effect of ICA is closely related to the Bcl-2 signaling pathway
.
Therefore, this study also conducted a TUNEL experiment to identify the expression of Bcl-2, Bax, and Caspase-3 related to the mitochondrial apoptosis pathway (Figure 6)
.
Compared with the control group, the number of apoptotic cells in the seminiferous tubules of the T2DM group was significantly increased, and the apoptotic signals were mainly concentrated in the peripheral area (Figure 6A, B)
.
The mRNA expressions of Bcl-2, Bax and Caspase-3 were significantly down-regulated and up-regulated, respectively (Figure 6C)
.

The normal development of germ cells and reproductive system is highly dependent on the regulation and balance of BCL-2 family proteins on mitochondrial apoptosis
.
Studies have confirmed that the anti-apoptotic effect of ICA is closely related to the Bcl-2 signaling pathway
.
Therefore, this study also conducted a TUNEL experiment to identify the expression of Bcl-2, Bax, and Caspase-3 related to the mitochondrial apoptosis pathway (Figure 6)
.
Compared with the control group, the number of apoptotic cells in the seminiferous tubules of the T2DM group was significantly increased, and the apoptotic signals were mainly concentrated in the peripheral area (Figure 6A, B)
.
The mRNA expressions of Bcl-2, Bax and Caspase-3 were significantly down-regulated and up-regulated, respectively (Figure 6C)
.

In contrast, the number of apoptotic cells in the ICA group and the metformin group was significantly reduced (Figure 6A and B), and the expression of Bcl-2, Bax and Caspase-3 mRNA were significantly up-regulated and down-regulated, especially in the ICA group (Figure 6C)
.

In contrast, the number of apoptotic cells in the ICA group and the metformin group was significantly reduced (Figure 6A and B), and the expression of Bcl-2, Bax and Caspase-3 mRNA were significantly up-regulated and down-regulated, especially in the ICA group (Figure 6C)
.

In summary, this study revealed that ICA may prevent DM-induced testicular dysfunction in rats by enhancing cell proliferation and inhibiting intrinsic mitochondrial-dependent apoptotic signals (Figure 7)
.
The results of this study show that ICA can effectively reduce male reproductive dysfunction and spermatogenesis induced by DM
.
ICA may improve spermatogenesis induced by DM by increasing the proliferation of spermatogonia, primary spermatocytes and supporting cells and inhibiting the mitochondrial-dependent apoptosis pathway
.
The results of this study indicate that ICA may be a potential new type of therapeutic drug to protect and treat SM-induced testicular injury
.

In summary, this study revealed that ICA may prevent DM-induced testicular dysfunction in rats by enhancing cell proliferation and inhibiting intrinsic mitochondrial-dependent apoptotic signals (Figure 7)
.
The results of this study show that ICA can effectively reduce male reproductive dysfunction and spermatogenesis induced by DM
.
ICA can effectively reduce the defects DM induced male reproductive dysfunction and spermatogenesis ICA can effectively reduce the DM-induced male reproductive dysfunction and spermatogenesis defects ICA possible by increasing spermatogonia, proliferation of primary spermatocytes and Sertoli cells, and inhibition of Mitochondrial-dependent apoptotic pathway to improve spermatogenesis defects induced by DM
.
The results of this study indicate that ICA may be a potential new type of therapeutic drug to protect and treat SM-induced testicular injury
.
ICA may be a potential new therapeutic drug to protect and treat SM-induced testicular injury ICA may be a potential new therapeutic drug to protect and treat SM-induced testicular injury

Original source:

He et al.
Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats.
Reproductive Biology and Endocrinology (2021) 19:168.
https://doi.
org/10.
1186 /s12958-021-00851-9

Leave a message here