Genetically Inherited Obesity and High-Fat Diet–Induced Obesity Differentially Alter Spermatogenesis in Adult Male Rats

Deshpande, Sharvari; Nemani, Harishankar; Palaniyandi, Suresh S.; Khambata, Kushaan; Kumar, Anita; Kallamadi, Prathap Reddy; Balasinor, Nafisa

doi:10.1210/en.2018-00569

Cited by 19 publications

(48 citation statements)

References 52 publications

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“…H&E staining analysis further indicated significant reduction in the number of spermatocytes and round spermatids in the seminiferous tubules (figure 1E, online supplementary table 3). These observations were in line with those reported elsewhere 8 14 31. Thus, the HFD treatment induced overt changes in metabolic parameters and the expected gut microbial dysbiosis and sperm quality.…”

Section: Resultssupporting

confidence: 92%

“…In particular, a recent study involving >10 000 subjects clearly demonstrated that the sperm quality, including sperm concentration, volume and motility, is negatively correlated with increased body mass index 12. In animal models, both genetically inherited and high-fat diet (HFD)-induced obesity impaired spermatogenesis 13 14. Furthermore, HFD could also lead to epigenetic disturbance15 in sperms as paternal inheritance of sperm tsRNAs could induce metabolic disorders in the F1 offspring 16…”

Section: Introductionmentioning

confidence: 99%

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Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Ding

Zhang²,

Zhang

et al. 2020

Gut

173

160

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ObjectiveHigh-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility.DesignFaecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin.ResultsTransplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice.ConclusionWe revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes.Trial registration numberNCT03634644.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Ding

Zhang²,

Zhang

et al. 2020

Gut

173

160

View full text Add to dashboard Cite

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“…The number of studies relating obesity to alterations in the parameters of spermiogenesis has begun to increase exponentially due to the low fertility observed in overweight and obese men [9, 28]. Recently, we informed that hypercholesterolemic rabbits showed sperm head defects under a HFD [3, 4].…”

Section: Discussionmentioning

confidence: 99%

“…Adiposity and associated pro-inflammatory status in male mice can induce testicular inflammation through activating several different signaling pathways [33]. This contributes to the deregulation of spermatogenesis and other functions of testicular cells [28, 34, 35]. Accordingly, our results indicate that chronic feeding of mice with a diet supplemented with chicken fat can cause systemic oxidative stress and inflammation, as well as a regional inflammatory reaction in the male genital tract, where the microenvironment is essential to support sperm production and function [7].…”

Section: Discussionmentioning

confidence: 99%

A chronic high-fat diet causes sperm head alterations in C57BL/6J mice

Funes

Lancellotti

Santillán

et al. 2019

Heliyon

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A chronic-positive energetic balance has been directly correlated with infertility in men, but the involved mechanisms remain unknown. Herein we investigated weather in a mouse model a chronic feeding with a diet supplemented with chicken fat affects sperm head morphology. To accomplish this, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat (high-fat diet, HFD). At the end of the feeding regimen, we measured: redox and inflammatory changes, cholesterol accumulation in testis and analyzed testicular morphological structure and ultra-structure and liver morphology. We found that the mice fed HFD resembled some features of the human metabolic syndrome, including systemic oxidative stress and inflammation, this group showed an increment in the following parameters; central adiposity (adiposity index: 1.07 AE 0.10 vs 2.26 AE 0.17), dyslipidemia (total cholesterol: 153.3 AE 2.6 vs 175.1 AE 8.08 mg/dL), insulin resistance (indirect Insulin resistance index, TG/HDL-c: 2.94 AE 0.33 vs 3.68 AE 0.15) and fatty liver. Increased cholesterol content measured by filipin was found in the testicles from HFD (fluorescence intensity increase to 50%), as well as an alteration of spermiogenesis. Most remarkably, a disorganized manchette-perinuclear ring complex and an altered morphology of the sperm head were observed in the spermatozoa of HFD-fed mice. These results add new information to our understanding about the mechanisms by which systemic oxidative stress and inflammation may influence sperm-head morphology and indirectly male fertility.

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“…Animal-based obesity models are predominantly of two types (1) genetic models which are based on mutations or manipulations of one or more genes and (2) genetically healthy animals which are exposed to obesogenic environments, mainly high calorie-rich diets [9]. Our earlier studies have shown the differential effects of highfat diet-induced (DIO) and genetically inherited obesity (GIO) on metabolic, biochemical and hormonal profiles, fertility parameters and spermatogenesis [10]. The study involved the use of WNIN/Ob mutant rats (Wistar origin) as the genetically inherited obese model and Wistar rat strain as the high-fat diet-induced obese model [10].…”

mentioning

confidence: 99%

High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats

Deshpande

Nemani

Gandhimathi³

et al. 2020

Clin Epigenet

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Background Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation. Results We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group. Conclusion Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.

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Genetically Inherited Obesity and High-Fat Diet–Induced Obesity Differentially Alter Spermatogenesis in Adult Male Rats

Cited by 19 publications

References 52 publications

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

A chronic high-fat diet causes sperm head alterations in C57BL/6J mice

High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats

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