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Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats - PubMed Skip to main page content
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. 2022 Jun 10;12(1):9633.
doi: 10.1038/s41598-022-13321-y.

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Samuel Oluwaseun Olojede  1 , Sodiq Kolawole Lawal  2 , Oluwaseun Samuel Faborode  3   4 , Ayobami Dare  3 , Okikioluwa Stephen Aladeyelu  2 , Roshila Moodley  5 , Carmen Olivia Rennie  2 , Edwin Coleridge Naidu  2 , Onyemaechi Okpara Azu  6
Affiliations

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Samuel Oluwaseun Olojede et al. Sci Rep. .

Abstract

Reproductive dysfunctions (RDs) characterized by impairment in testicular parameters, and metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM) are on the rise among human immunodeficiency virus (HIV) patients under tenofovir disoproxil fumarate (TDF) and highly active antiretroviral therapy (HAART). These adverse effects require a nanoparticle delivery system to circumvent biological barriers and ensure adequate ARVDs to viral reservoir sites like testis. This study aimed to investigate the effect of TDF-loaded silver nanoparticles (AgNPs), TDF-AgNPs on sperm quality, hormonal profile, insulin-like growth factor 1 (IGF-1), and testicular ultrastructure in diabetic rats, a result of which could cater for the neglected reproductive and metabolic dysfunctions in HIV therapeutic modality. Thirty-six adult Sprague-Dawley rats were assigned to diabetic and non-diabetic (n = 18). T2DM was induced by fructose-streptozotocin (Frt-STZ) rat model. Subsequently, the rats in both groups were subdivided into three groups each (n = 6) and administered distilled water, TDF, and TDF-AgNP. In this study, administration of TDF-AgNP to diabetic rats significantly reduced (p < 0.05) blood glucose level (268.7 ± 10.8 mg/dL) from 429 ± 16.9 mg/dL in diabetic control and prevented a drastic reduction in sperm count and viability. More so, TDF-AgNP significantly increased (p < 0.05) Gonadotropin-Releasing Hormone (1114.3 ± 112.6 µg), Follicle Stimulating Hormone (13.2 ± 1.5 IU/L), Luteinizing Hormone (140.7 ± 15.2 IU/L), testosterone (0.2 ± 0.02 ng/L), and IGF-1 (1564.0 ± 81.6 ng/mL) compared to their respective diabetic controls (383.4 ± 63.3, 6.1 ± 1.2, 76.1 ± 9.1, 0.1 ± 0.01, 769.4 ± 83.7). Also, TDF-AgNP treated diabetic rats presented an improved testicular architecture marked with the thickened basement membrane, degenerated Sertoli cells, spermatogenic cells, and axoneme. This study has demonstrated that administration of TDF-AgNPs restored the function of hypothalamic-pituitary-gonadal axis, normalized the hormonal profile, enhanced testicular function and structure to alleviate reproductive dysfunctions in diabetic rats. This is the first study to conjugate TDF with AgNPs and examined its effects on reproductive indices, local gonadal factor and testicular ultrastructure in male diabetic rats with the potential to cater for neglected reproductive dysfunction in HIV therapeutic modality.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
This figure illustrates the blood glucose level of the treated groups and control. As shown in Fig. 1., the blood glucose level in diabetic control rats were significantly increased compared with non-diabetic control. Also, administration of TDF-AgNP to diabetic rats significantly reduced the blood glucose levels compared with diabetic control rats and rats treated with TDF.
Figure 2
Figure 2
This figure describes the sperm count (A) and sperm viability (B) of the treated groups and control. As shown in (A,B), the sperm count and sperm viability in diabetic control groups were significantly reduced compared with their relative non-diabetic control groups. There were no significant differences in the sperm count and viability in DNT compared with DC.
Figure 3
Figure 3
This figure demonstrates the results of the hormonal assays of the (A) Gonadotropin-Releasing Hormone (GnRH), (B) Follicle-stimulating hormone (FSH), (C) Luteinizing hormone (LH) and (D) testosterone for the treated groups and control. In (A–D), the hormonal profile (GnRH, FSH, LH, Testosterone) of the diabetic control groups were significantly reduced compared with their respective non-diabetic control groups. More so, administration of TDF-AgNP to diabetic rats significantly increases GnRH, FSH, LH and Testosterone compared with diabetic control groups.
Figure 4
Figure 4
The testicular insulin-like growth factor 1 (IGF-1) of the treated groups and control. As revealed in Fig. 4, the IGF-1 level was significantly reduced in the diabetic control group compared with the non-diabetic control group. The level of testicular IGF-1 was significantly increased compared with the diabetic control group following the administration of TDF-AgNP.
Figure 5
Figure 5
(a) The ultrastructure of rat testicular basement membrane across the treatment and control groups (Scale bar-5 µm). The TEM images of all the non-diabetic groups (NDC, NDT and NDNT) show well delineated basement membrane (Bm) without alterations. The ultrastructure of diabetic control rat displays thickened basement membrane and myoid cell. The basement membranes of DT and DNT groups show normal orientation. (b) The ultrastructure of rat testicular Sertoli and Spermatogenic cells in treated and control groups (Scale bar-10 µm). The TEM images of NDC, NDT and NDNT show a normal Sertoli cell (Sc) and Spermatogenic cells (Spermatogonia Sg, Primary spermatocyte Sp, Secondary spermatocyte Ss) in different stages of development. Ultrastructure of DC shows a degenerated Sertoli and Spermatogenic cells while DT displays degenerated spermatogonia cell. The TEM image of DNT shows an improvement in the Sertoli and Spermatogenic cells. (c) The ultrastructure of rat’s mature sperm middle piece across the treatment and control groups (Scale bar-5 µm). The ultrastructure of NDC, NDT and NDNT shows normal sperm axoneme characterized by central microtubules (white arrows) and nine (9) pairs peripheral microtubules encircled by the outer dense fibrils (orange arrows). Also, the concentric sperm axonemes were surrounded by the plasma membrane (PM). TEM images of DC and DT show degenerated axoneme (green arrow) nuclear membrane (blue arrow), acrosomal membrane (AM) and plasma membrane. The TEM image of DNT shows enhancement in the axonemes with little degeneration (green arrow).
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