How Does Obesity Affect Male Fertility?

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In a recently published review, researchers summarize the effects of paternal obesity on male fertility — specifically sperm quality and progeny health.

Obesity, defined as the excessive accumulation of adipose tissue, is a well-established risk factor for many pathologies, including hypertension, kidney and cardiovascular disease, and type II diabetes. Recent studies have shown that obesity can also affect sperm quality, progeny health, and increase the risk of infertility. A recent review by Raad and colleagues published in Basic and Clinical Andrology summarizes the effects of paternal obesity on male fertility, sperm quality, and progeny health.

Obesity Alters Seminal Plasma

The seminal plasma is a gelatinous fluid, made of seminal vesicle and prostate gland secretions, that is vital for proper sperm transport and survival. Furthermore, seminal fluid can regulate gene expression in the female oviduct, a tube through which the egg passes. Recent studies have shown that obese men exhibit altered seminal plasma volume and composition, which could negatively affect sperm biology. For instance, elevated fructose and interleukin-8 levels in obese men have been correlated with increased sperm DNA damage and poor progeny health, respectively.

Effects of Obesity on Testosterone and Production of Sperm

The Leydig cells of the testes are responsible for secreting testosterone, a steroid hormone that has a well-established role in sperm production or spermatogenesis. Altered glucose and lipid levels in obese men have been shown to alter Leydig cell function, thereby inhibiting testosterone production and impairing spermatogenesis.

Furthermore, obese men may have altered levels of sex hormone binding globulin (SHBG) production, which normally binds free circulating testosterone in the blood and regulates testosterone clearance and access to target tissues. Obesity-induced alterations in sex hormone binding globulin levels increase free testosterone levels in the blood, thereby increasing testosterone conversion into estrogen. The hormone estrogen can inhibit upstream signaling pathways that ultimately impair testosterone production.

The Sertoli cells are another cell type in the testes, responsible for regulating spermatogenesis in response to follicle stimulating hormone (FSH) and testosterone. Studies show that obese men have lower FSH levels and altered Sertoli cell metabolism, which contribute to impaired spermatogenesis and increased reactive oxidative species (ROS), respectively. Obesity-associated ROS can damage Sertoli cells and consequently impair proper sperm production.

Although human studies investigating obesity and embryo development are scarce, studies in rodents demonstrate that obesity negatively impacts pre-implantation embryo development. Furthermore, a meta-analysis of 115,158 participants showed that paternal obesity may reduce live birth rate per assisted reproductive technology (ART) cycle and increase the risk of non-viable pregnancies. Collectively, there is a lot of evidence to suggest that obesity compromise fertility, sperm production, and sperm quality.

High-Fat Diets May Affect Offspring

This review also summarized the proposed genetic and epigenetic mechanisms by which paternal obesity may influence progeny health. Although human studies investigating inheritance are difficult, rodent models have given rise to several hypotheses regarding how paternal obesity may negatively affect progeny. For instance, researchers argue that certain DNA methylation signatures attained through high-fat diets may be partially transmitted to offspring.

Another proposed method of inheritance could be through paternal histones, defined as proteins around which DNA coils. In sperm, DNA is wrapped around proteins called protamines, and condensed into chromatins. Upon fertilization, the majority of the protamines are replaced by maternal histones, while 5 to 10% are replaced by paternal histones. These paternal histones could be the inherited epigenetic regulator of diet-induced obesity. Finally, recent studies have shown that sperm contains RNA populations that may play crucial roles in embryo development and epigenetic inheritance.

In conclusion, this study highlights several mechanisms by which paternal obesity may affect male fertility, specifically by impairing sperm production and reducing sperm quality. Moreover, they summarize several different mechanisms of inheritance, most of which are based on rodent studies. Further research is required to test the difference methods of inheritance.

Written by Haisam Shah, BSc

 

Citation: Raad, G., Hazzouri, M., Bottini, S., Trabucchi, M., Azoury, J., & Grandjean, V. (2017). Paternal obesity: how bad is it for sperm quality and progeny health?. Basic and Clinical Andrology27(1), 20.

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