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Obesity is emerging as a potential risk factor for male infertility. It is a multifactorial disorder with primarily genetic and/or environmental factors. Our earlier studies have shown differential effects of genetically inherited-and high fat diet induced-obesity on hormones, fertility and spermatogenesis in adult male rats. In the present study, we assessed the effect of high fat diet induced – and genetically inherited – obesity on the underlying molecular mechanisms affecting spermatogenesis. The expression of hormone receptors, cytokines and markers of oxidative stress as well as cell cycle mediators were affected in both the obese groups, however, the changes were different in the two groups. This could be due to difference in fat distribution between the two types of obese groups. Altered expression of hormone receptors, cytokines, cell cycle mediators and differential effects on oxidative stress could be the plausible reason for differential changes in germ cell population in both the groups.

Obesity is a multifactorial disorder with predominantly genetic and/or environmental causes. Our aim was to delineate effects of genetically inherited and high-fat diet-induced obesity on fertility and spermatogenesis using two Wistar rat models: genetically inherited obese (GIO) WNIN/Ob rats and diet-induced obese (DIO) rats, which received a high-fat diet. The terminal body weights were similar in both groups, but there was a significant difference in metabolic and hormone profiles between the groups. Fertility assessment revealed a significant decrease in the litter size due to increased pre- and postimplantation loss in the DIO group, whereas the rats in the GIO group were infertile due to lack of libido. Significantly decreased sperm counts were observed in the GIO group compared with the DIO group. Enumeration of testicular cells on the basis of ploidy and cell type-specific expression markers, to study the effect of obesity on spermatogenesis, demonstrated that the GIO and DIO states affected mitosis: spermatogonia and S-phase population were increased. However, distinctive effects were observed on meiosis and spermiogenesis in both the groups. Differential effects of GIO and DIO on fertility and spermatogenesis could be due to the significant difference in white adipose tissue accumulation between the groups and not due to high body weights. The differential effects of obesity suggest male obesity-induced infertility observed in humans could be a combination of genetic and environmental factors.

Obesity is a multifactorial condition with predominantly genetic and environmental causes and is an emerging risk factor for male infertility/subfertility. Epigenetic mechanisms are vulnerable to genetic and environmental changes. Our earlier studies have shown differential effects of genetically inherited (GIO) - and diet-induced- obesity (DIO) on DNA methylation in male germline. Contrary to DNA methylation is DNA demethylation, which also regulates the gene expression by activating transcription. The present study aimed to delineate the effects of obesity on the DNA demethylation pathway using two rat models: GIO (WNIN/Ob) and DIO (high-fat diet). We observed differential alterations in enzymes involved in DNA demethylation by oxidation (Tet1-3) pathway in testis in both groups. An increase in Tets in DIO group and a decrease in GIO group were noted. Analysis of oxidation pathway intermediates (5-hmC, 5-fC, and 5-caC) did not show any effect on testis in DIO group but an increase in 5-hmC and decrease in 5-caC levels in GIO group was observed. Analysis of transcript levels of enzymes related to deamination pathway in testis showed an increase (Gadd45a, Aicda, and Tdg) in DIO group and a decrease (Gadd45a, Aicda, and Tdg) in GIO group. Also, 5-hmC levels were differentially altered in the spermatozoa of both groups without any changes in Tetenzyme levels. These findings highlight differences in effects of GIO and DIO on DNA demethylation mechanisms in male germline, which could be due to differences in endocrine and metabolic profile as well as white fat distribution observed earlier in two groups.