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. 2023 Aug 7;17(4):268-275.
doi: 10.22074/ijfs.2022.544368.1235.

Forskolin Improves Male Reproductive Complications Caused by Hyperglycemia in Type 2 Diabetic Rats

Mehran Naghibi  1   2 , Hamid Tayefi Nasrabadi  2 , Jafar Soleimani Rad  2 , Alireza Garjani  3 , Mohammad Sadegh Gholami Farashah  2   4 , Daryoush Mohammadnejad  1   5
Affiliations

Forskolin Improves Male Reproductive Complications Caused by Hyperglycemia in Type 2 Diabetic Rats

Mehran Naghibi et al. Int J Fertil Steril. .

Abstract

Background: In many diabetic patients, spermatogenesis complications are frequent causing infertility problems. This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes.

Materials and methods: In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for one month and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats with more than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided into four groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2 (G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphate buffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month.

Results: In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly: The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Bax gene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone (P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008), sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 gene expression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values that was significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantly improved these abnormal changes in Forskolin-treated group.

Conclusion: Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improves sperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Keywords: FORSKOLIN; Male Infertility; Oxidative Stress; Testicular Dysfunction; Type 2 Diabetes.

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Figures

Fig.1
Fig.1
Effects of forskolin on blood sugar and body weight indexes in different time periods. Comparision of A. Blood sugar and B. Body weight in different experimental groups: control group (G1), diabetic control group (G2), vehicle control group (G3) and Forskolin-treated diabetic group (G4). There are ten rats in each group. One-way ANOVA test was used and all values were presented as mean ± SD. Values with various superscripts are significantly different. a; indicates significant difference between the G1 with G2, G3, and G4 groups after HFD (P<0.001), b; Indicates significant difference between the G1 with G2, G3, and G4 groups after STZ treatment (P<0.001), c; Indicates significant difference between the G1 with G2, G3, and G4 groups after Forskolin treatment (P<0.001), d; Indicates significant difference between the G4 with G2 after Forskolin treatment (P<0.001), e; Indicates significant difference between the G4 with G3 after Forskolin treatment (P<0.001), and *; Indicates significant difference among different treatment of the G2, G3, and G4 groups (P<0.001), HFD; High-fat diet, and STZ; Streptozotocin.
Fig.2
Fig.2
Effects of Forskolin on sperm parameters in different experimental groups. A. Sperm concentration (×106 /ml), B. Normal sperm morphology (%), and C. Sperm motility (%). Control group (G1), diabetic control group (G2), vehicle control group (G3) and Forskolin-treated diabetic group (G4). There were ten rats in each groups. One-way ANOVA test was used. Data represented as mean ± SD. Significant difference with * ; P<0.001, # ; P<0.0001, HFD; High-fat diet, and STZ; Streptozotocin.
Fig.3
Fig.3
Effect of Forskolin on serum levels of gonadotropins and testosterone. Comparison of A. LH, B. FSH, and C. Testosterone hormones among different groups. Control group (G1), diabetic control group (G2), vehicle control group (G3) and Forskolin treated diabetic group (G4). There were ten rats in each groups. One-way ANOVA test was used. Data represented as mean ± SD. Significant difference with *; P<0.05, #; P<0.01, $ ; P<0.001, LH; Luteinizing hormone, and FSH; Follicle-stimulating hormone.
Fig.4
Fig.4
Effect of Forskolin on testicular levels of oxidative markers. Comparison of the A. SOD, B. GPx, and C. MDA levels in the testis tissue among study groups. Control group (G1), diabetic control group (G2), vehicle control group (G3) and Forskolin treated diabetic group (G4). There were ten rats in each groups. One-way ANOVA test was used. Data represented as mean ± SD. Significant difference with *; P<0.001, #; P<0.0001, SOD; Superoxide dismutase, GPx; Glutathione peroxidase, and MDA; Malondialdehyde.
Fig.5
Fig.5
Effect of Forskolin on the expression of Bax and Bcl-2 genes. The mRNA expression of A. Bax, B. Bcl-2, C. Their ratio in different groups as well as D. Applied primer sequences. Control group (G1), diabetic control group (G2), vehicle control group (G3) and Forskolin treated diabetic group (G4). There were ten rats in each groups. Expression level of genes (Bax and Bcl-2) were evaluated regarding the housekeeping gene (GAPDH). One-way ANOVA test was used. Significant difference with *; P<0.001, #; P<0.0001, and $; Non-significant.
Fig.6
Fig.6
The histological finding in testicular sections and seminiferous tubular indices. A. Photomicrograph of testicular tissue sections showing morphological characteristics of seminiferous tubules in different groups. A1. Control group, A2. Diabetic control group, A3. Vehicle control group, and A4. Forskolin treated diabetic group. B1. Seminiferous tubule diameter (STD), B2. Height of germinal epithelium (HE), and B3. Mean Johnsen score (MJS)] in different groups. G1; Control group, G2; Diabetic control group, G3; Vehicle control group, G4; Forskolin treated diabetic group. There were ten rats in each group. One-way ANOVA test was used and data represented as mean ± SD. S; Sertoli cell, SG; Spermatogonia, PS; Primary spermatocyte, IS; Immature spermatid, MS; Mature spermatid, * ; Space and +; Hemorrhage. HɬE staining (scale bar: 50 µm, magnification: 400x). Significant difference with *; P<0.05, #; P<0.01 and $; P<0.001.
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