Functional relationship between obesity and male reproduction: from humans to animal models

Teerds, Katja J.; Rooij, Dirk G. de; Keijer, Jaap

doi:10.1093/humupd/dmr017

Cited by 159 publications

(129 citation statements)

References 140 publications

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“…Several animal models had been used to demonstrate the importance of leptin in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis [23]. An adequate concentration of leptin is necessary for normal reproductive function, while overproduction of leptin, resulting in hormonal resistance, may be an important mechanism of androgen deficiency in obese men [24].…”

Section: Discussionmentioning

confidence: 99%

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Yan

et al. 2015

J Assist Reprod Genet

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Purpose The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention. Methods Male Sprague-Dawley rats (n=18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL. Results Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P<0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P<0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P<0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P<0.05). Conclusions HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

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Section: Discussionmentioning

confidence: 99%

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Yan

et al. 2015

J Assist Reprod Genet

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“…Genetically obese leptin-receptor-deficient mice as well as dietary obese leptin-resistant mice showed lowered Mup1 levels [38,39]. As mediators of reproduction, decreased Mup levels are probably responsible for the observed infertility of these mice [49] and in leptindeficient obese mice (ob/ob), reproduction parameters were normalized by leptin administration [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

et al. 2013

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Major urinary proteins (Mups) are important for rodent scent communication and sexual behaviour. Recent evidence suggests that Mup1 may be regulated by fasting and re-feeding (RF). However, other Mup isoforms are poorly investigated, and data on the impact of long-term dietary restriction (DR) and ad libitum RF on Mup expression are missing. We investigated the effects of long-term 25 per cent DR and subsequent RF on Mup expression in male C57BL6 mice. DR significantly decreased Mup gene expression, hepatic and urinary protein levels compared with ad libitum (AL) fed control mice, with the greatest downregulation found for Mup5 expression. The decline in Mup expression was inverted by six months of RF. Because of inhibitory glucocorticoid response elements in the genomic sequence of the Mup5 gene, the observed inverse correlation of nuclear glucocorticoid receptor levels with Mup expression in response to DR and subsequent RF is a possible regulatory mechanism. Additionally, gene-expression-inhibiting histone deacetylation (H3K9) occurred in the region of the Mup5 gene in response to DR. We assume that Mup may act as a molecular switch linking nutritional status to sexual behaviour of mice, and thereby regulating male fertility and reproduction in response to food supply.

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“…Recent studies have shown that the secretion of adipokines, such as leptin from adipose tissue, regulates reproductive function by affecting the hypothalamuspituitary-gonadal (HPG) axis (1,2). Evidence for a link between adipose tissue function and male fertility has also emerged from several studies showing a negative impact of obesity on male reproduction (3,4). Whether the opposing syndrome, loss of adipose tissue, or lipodystrophy impacts on male infertility remains largely unexplored.…”

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confidence: 99%

Lack of testicular seipin causes teratozoospermia syndrome in men

Jiang

Gao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Obesity impairs male fertility, providing evidence for a link between adipose tissue and reproductive function; however, potential consequences of adipose tissue paucity on fertility remain unknown. Lack of s.c. fat is a hallmark of Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), which is caused by mutations in BSCL2-encoding seipin. Mice with a targeted deletion of murine seipin model BSCL2 with severe lipodystrophy, insulin resistance, and fatty liver but also exhibit male sterility. Here, we report teratozoospermia syndrome in a lipodystrophic patient with compound BSCL2 mutations, with sperm defects resembling the defects of infertile seipin null mutant mice. Analysis of conditional mouse mutants revealed that adipocyte-specific loss of seipin causes progressive lipodystrophy without affecting fertility, whereas loss of seipin in germ cells results in complete male infertility and teratozoospermia. Spermatids of the human patient and mice devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phosphatidic acid accompanied with an altered ratio of polyunsaturated to monounsaturated and saturated fatty acids in mutant mouse testes indicate impaired phospholipid homeostasis during spermiogenesis. We conclude that testicular but not adipose tissue-derived seipin is essential for male fertility by modulating testicular phospholipid homeostasis.

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Functional relationship between obesity and male reproduction: from humans to animal models

Abstract: Infertility in overweight/obese males may be explained by leptin insensitivity. This implies a possible role for the KISS1 system in human obesity-related male infertility. If substantiated, it will pave the way for methods to restore fertility in these subjects.

Cited by 159 publications

References 140 publications

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

Lack of testicular seipin causes teratozoospermia syndrome in men

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