Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes

Sajadi, Ensieh; Dadras, Sara; Bayat, Mohammad; Abdi, Shabnam; Nazarian, Hamid; Ziaeipour, Sanaz; Mazini, Fatemeh; Kazemi, Mahsa; Bagheri, Mohammad; Valizadeh, Aida; Abdollahifar, Mohammad‐Amin

doi:10.1002/jcb.28995

Cited by 22 publications

(18 citation statements)

References 30 publications

(109 reference statements)

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“…In line with other reports regarding the effect of hyperthermia on spermatogenesis (Chen et al., 2008; Edelman, 1986, 1988; Fraser et al., 1987; Fujisawa, 2006; Li et al., 2013; Sajadi et al., 2019; Vera et al., 2004), our findings confirm that transient scrotal hyperthermia can markedly decrease sperm count, sperm motility and sperm viability and impair sperm morphology. In this study, serum testosterone level shrank significantly in mice induced by scrotal hyperthermia.…”

Section: Discussionsupporting

confidence: 92%

“…Many studies have assessed the effect of hyperthermia on physiological and cellular responses of testicular tissue and its corresponding mechanism based on animal models (Edelman, 1986, 1988; Fraser, Green, Bode, & Gilula, 1987; Sajadi et al., 2019). However, there is a paucity of studies on cellular interaction and spatial arrangement of testicular cells.…”

Section: Discussionmentioning

confidence: 99%

“…We need to normalize the cross‐covariance in order to eliminate volume fraction differences by assessing cross‐correlation function by the formula below (Krasnoperov & Stoyan, 2004; Torsten Mattfeldt et al., 2006; Mattfeldt et al., 1993; Mayhew, 1999; Sajadi et al., 2019):

g false(r false) X Y = \frac{C (r) X Y}{V_{normalv} false(X ref false) \times V_{normalv} false(Y ref false)}

…”

Section: Methodsmentioning

confidence: 99%

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Spatial arrangement of testicular cells disrupted by transient scrotal hyperthermia and subsequent impairment of spermatogenesis

et al. 2020

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Spermatogenesis is a complex process that occurs in adult spermatozoa following the proliferation and differentiation of spermatogonia cells. The testicles, as the site of the spermatogenesis process, should be placed outside the body cavity at a temperature of 2 to 8°C below the body temperature to yield the best performance (Hess & De Franca, 2008). On the other hand, spermatogenesis is an extremely temperature-dependent process such that the increased testicular temperature may disrupt this process, damage the DNA of germ cells and increase cell death (Wang et al., 1997). In recent years, many studies have reported adverse and deleterious effects of scrotum heat stress on sperm parameters and the spermatogenesis process in various species, including humans, mice, rats, sheep, pigs and cows. The findings also suggest that thermal shock affects the quality of

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

g false(r false) X Y = \frac{C (r) X Y}{V_{normalv} false(X ref false) \times V_{normalv} false(Y ref false)}

…”

Section: Methodsmentioning

confidence: 99%

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Spatial arrangement of testicular cells disrupted by transient scrotal hyperthermia and subsequent impairment of spermatogenesis

et al. 2020

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“…By calculating the extent of spatial mixing and pairwise cell-cell contact frequencies between different cell types, we observed a significant disruption in spatial cellular organization of the diabetic seminiferous tubules. Of interest, a previous study using second order stereology has indicated that the spatial arrangement of Sertoli cells and spermatogonia is significantly disrupted in the diabetic testes (Sajadi et al, 2019). Indeed, our analysis showed a significant change in the spatial contact frequencies between Sertoli cells and spermatogonia.…”

Section: The Spatial Transcriptome Atlas As a Platform To Profile Spasupporting

confidence: 46%

Dissecting Mammalian Spermatogenesis Using Spatial Transcriptomics

Chen

Murray

Laumas

et al. 2020

Preprint

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Single-cell RNA sequencing has revealed extensive molecular diversity in gene programs governing mammalian spermatogenesis but fails to delineate their dynamics in the native context of seminiferous tubules - the spatially-confined functional units of spermatogenesis. Here, we use Slide-seq, a novel spatial transcriptomics technology, to generate a comprehensive spatial atlas that captures the spatial gene expression patterns at near single-cell resolution in the mouse and human testis. By using Slide-seq data, we devise a computational framework that accurately localizes testicular cell types in individual seminiferous tubules. Unbiased spatial transcriptome analysis systematically identifies spatially patterned genes and gene programs, nominating genes with previously underappreciated but important functions in spermatogenesis. Using the human testicular spatial atlas, we identify two spatially segregated spermatogonial populations composed of stem cells at distinct transcriptional states. Finally, a comparison of the spatial atlas generated from the wild type and diabetic mouse testis reveals a disruption in the spatial cellular organization in diabetic seminiferous tubules.

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“…Instead, we employed immunohistochemistry for distinct proteins of the BTB. Amongst others, ZO-1, claudin 11, and CX43 are structural components of the inter Sertoli cell junctions, which undergo alterations in conjunction with impairment of spermatogenesis [32,[34][35][36][37]. As shown by Rode et al [38], loss of CX43 in mouse Sertoli cells leads to spermatogenic arrest at the level of spermatogonia with only single primary spermatocytes.…”

Section: Discussionmentioning

confidence: 99%

Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia – adverse effect of clomiphene citrate pre-treatment?

Fietz

Pilatz

Diemer

et al. 2020

Basic Clin. Androl.

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Background: Clomiphene citrate has been proposed as pre-treatment for infertile men with non-obstructive, testicular azoospermia (NOA) before surgery for testicular sperm extraction (TESE), especially when serum testosterone is low. Case presentation: Here, we report on a 33-year old azoospermic patient with a previous history of repeated "fresh" TESE and clomiphene citrate therapy (50 mg/day over 6 months) before undergoing microscopically assisted, bilateral testicular biopsy. Comprehensive histological and immunohistochemical work-up revealed a heterogeneous spermatogenic arrest at the level of spermatogonia or primary spermatocytes, with focally preserved spermatogenesis up to elongated spermatids in the right testis. In the left testis, the majority of tubules (> 70%) showed no tubular lumen or regular seminiferous epithelium but a great number of spermatogonia-like cells. These cells proved to be normally differentiated spermatogonia (positive for melanoma associated antigen 4 (MAGEA4), negative for placental alkaline phosphatase (PlAP)) with increased proliferative activity (positive for proliferating cell nuclear antigen (PCNA)) and a slightly higher rate of apoptotic cells. When compared to a tissue control with normal spermatogenesis, expression of sex hormone receptors androgen receptor (AR), estrogen receptor (ER) alpha, and G-protein coupled estrogen receptor 1 (GPER1) was not altered in patient samples. Sertoli cells appeared to be mature (positive for vimentin, negative for cytokeratin 18), whereas the expression of zona occludens protein 1 (ZO-1), claudin 11, and connexin 43 was absent or dislocated in the tubules with abundance of spermatogonia. Conclusion: This result suggests that formation of the blood-testis barrier is disturbed in affected tubules. To our knowledge this is the first observation of excessive, non-malignant proliferation of spermatogonia in a NOA patient. Although underlying molecular mechanisms remain to be elucidated, we hypothesize that the unusual pathology was triggered by the high-dose clomiphene citrate treatment preceding testicular biopsy.

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Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes

Cited by 22 publications

References 30 publications

Spatial arrangement of testicular cells disrupted by transient scrotal hyperthermia and subsequent impairment of spermatogenesis

Spatial arrangement of testicular cells disrupted by transient scrotal hyperthermia and subsequent impairment of spermatogenesis

Dissecting Mammalian Spermatogenesis Using Spatial Transcriptomics

Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia – adverse effect of clomiphene citrate pre-treatment?

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