**3.1 Hormonal effects of male obesity**

Much like in the female, the hypothalamic-pituitary-gonadal (HPG) axis is dysregulated in the setting of male obesity. There is strong evidence of a negative effect of obesity on total testosterone, SHBG, and free testosterone [46] as well as reduced inhibin B concentrations and diminished luteinizing hormone (LH) pulse amplitude [4]. It is well understood that suppression of SHBG by hyperinsulinemia in obese men increases androgen availability for aromatization to estrogen in adipose tissue, which may then lead to negative feedback and reduction in gonadotrophin secretion [4]. Consequent to this is a decreased Leydig cell testosterone secretion, which ultimately affects spermatogenesis.

The function of the Sertoli cell, which provides both physical and nutritional support to the developing germ cell, is also impacted. Adhesion of the Sertoli cell is dependent on testosterone, and a reduction in these levels can lead to retention and phagocytosis of mature spermatids and ultimately reduced sperm counts. Other hormones that influence Sertoli cell function, FSH, LH, inhibin B, and SHBG are all lower in obese men [47].

#### **3.2 Effects of obesity on spermatogenesis**

The best markers to assess the impact of obesity on spermatogenesis are the sperm parameters from the semen analysis (count, motility, and morphology). Rodent models clearly demonstrate that diet-induced male obesity leads to reduced sperm motility, decreased sperm count, and decreased percentage of sperm with normal morphology [47], though some argue that this is indirectly due to altered hormonal stimulation.

The impact of male obesity on sperm parameters in humans is more controversial, with many contradicting studies. A review of studies [47] demonstrated varying results for the impact of male obesity on sperm concentration, morphology, and motility. The reviewers commented that there were several significant confounders including lifestyle factors such as smoking and alcohol consumption as well as cofactors such as the metabolic syndrome, which have all been shown to impact on sperm parameters. Most of the cohorts studied come from fertility centers and so are biased toward subfertile men, who may differ from the background population. Additionally, many studies rely on self-reporting, which can lead to inaccuracies.

A recent systematic review that evaluated 21 studies demonstrated a J-shaped correlation between male obesity and sperm count, whereby overweight and obesity is associated with higher rates of oligozoospermia and azoospermia [48].

#### **3.3 Effects of obesity on sperm DNA integrity**

In addition to sperm parameters, sperm DNA integrity has been found to be an important factor for the ability of a sperm to generate a healthy pregnancy [49]. Reactive oxygen species (ROS), commonly elevated in subfertile men, have been found to impair sperm DNA integrity. This is likely due to the fact that sperm are highly susceptible to ROS in the later stages of spermiogenesis as they lose the majority of their antioxidant defenses when they shed cytoplasm (**Figure 1**).

Studies have demonstrated that there is a positive correlation between increasing adiposity and higher sperm and seminal plasma ROS levels [50–52]. Oxidative stress is highly correlated with cumulative damage in the body induced by free radicals that are inadequately neutralized by antioxidant mechanisms. Antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). A recent study in an obese mouse model showed decreased SOD in the testicular tissues of obese rats [53].

Studies have also confirmed that male obesity is associated with higher levels of sperm DNA damage [47], due to the oxygen-free radical damage, and a direct thermal effect on the testicles due to obesity. It is therefore a reasonable assumption that male obesity negatively impacts on sperm DNA integrity via high ROS levels within the testis. DNA fragmentation has been proven to reduce male fertility, possibly reduce success with assisted reproduction, and increase pregnancy loss.

Although not directly impacting on testicular function, obesity leading to reduced testosterone results in a reduction in libido and negatively impacts on erectile and ejaculatory function, which all lead to a reduction in fecundity [54].

**61**

**Figure 1.**

*Reproductive Consequences of Obesity*

*DOI: http://dx.doi.org/10.5772/intechopen.80897*

**4. Transgenerational effects of parental obesity**

the maternal or the paternal line.

There is good evidence to show that maternal obesity during pregnancy is a risk factor for obesity in the offspring [55]. There is also an increasing body of evidence that obesity in males and females periconceptionally can impact on the metabolic health and even fertility of future generations. By using animal models, the impact of maternal and paternal obesity on offspring and future generations has been examined. Studies have demonstrated that obesity and other health conditions can be transmitted across multiple generations via epigenetic mechanisms down either

*Hypothesis on how epigenetic changes and impact of ROS due to an obese proinflammatory environment can occur at multiple different points along the development of the sperm, resulting in altered fertility [47].*

An elegant murine study by Huypens and others [56] induced obesity in both male and female parents for 6 weeks with a high-fat diet (HFD) and then performed IVF. Embryos created from all combinations of parents were transferred into a lean

Female offspring born from both maternal and paternal obese parents gained more weight than the male offspring. The risk of female offspring obesity was reduced if only the female parent was obese, suggesting an additive effect.

Females from obese parents also had significant metabolic derangements. They demonstrated a delay in blood glucose clearance leading to hyperinsulinemia and increased fat mass. Male offspring demonstrated severe insulin resistance before

dam, to negate the impact of obesity during pregnancy (**Figure 2**).

*Obesity*

lower in obese men [47].

hormonal stimulation.

**3.2 Effects of obesity on spermatogenesis**

**3.3 Effects of obesity on sperm DNA integrity**

testicular tissues of obese rats [53].

The function of the Sertoli cell, which provides both physical and nutritional support to the developing germ cell, is also impacted. Adhesion of the Sertoli cell is dependent on testosterone, and a reduction in these levels can lead to retention and phagocytosis of mature spermatids and ultimately reduced sperm counts. Other hormones that influence Sertoli cell function, FSH, LH, inhibin B, and SHBG are all

The best markers to assess the impact of obesity on spermatogenesis are the sperm parameters from the semen analysis (count, motility, and morphology). Rodent models clearly demonstrate that diet-induced male obesity leads to reduced sperm motility, decreased sperm count, and decreased percentage of sperm with normal morphology [47], though some argue that this is indirectly due to altered

The impact of male obesity on sperm parameters in humans is more controversial, with many contradicting studies. A review of studies [47] demonstrated varying results for the impact of male obesity on sperm concentration, morphology, and motility. The reviewers commented that there were several significant confounders including lifestyle factors such as smoking and alcohol consumption as well as cofactors such as the metabolic syndrome, which have all been shown to impact on sperm parameters. Most of the cohorts studied come from fertility centers and so are biased toward subfertile men, who may differ from the background population. Additionally, many studies rely on self-reporting, which can lead to inaccuracies. A recent systematic review that evaluated 21 studies demonstrated a J-shaped correlation between male obesity and sperm count, whereby overweight and obesity is associated with higher rates of oligozoospermia and azoospermia [48].

In addition to sperm parameters, sperm DNA integrity has been found to be an important factor for the ability of a sperm to generate a healthy pregnancy [49]. Reactive oxygen species (ROS), commonly elevated in subfertile men, have been found to impair sperm DNA integrity. This is likely due to the fact that sperm are highly susceptible to ROS in the later stages of spermiogenesis as they lose the majority of their antioxidant defenses when they shed cytoplasm

Studies have demonstrated that there is a positive correlation between increasing adiposity and higher sperm and seminal plasma ROS levels [50–52]. Oxidative stress is highly correlated with cumulative damage in the body induced by free radicals that are inadequately neutralized by antioxidant mechanisms. Antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). A recent study in an obese mouse model showed decreased SOD in the

Studies have also confirmed that male obesity is associated with higher levels of sperm DNA damage [47], due to the oxygen-free radical damage, and a direct thermal effect on the testicles due to obesity. It is therefore a reasonable assumption that male obesity negatively impacts on sperm DNA integrity via high ROS levels within the testis. DNA fragmentation has been proven to reduce male fertility, possibly

reduce success with assisted reproduction, and increase pregnancy loss.

Although not directly impacting on testicular function, obesity leading to reduced testosterone results in a reduction in libido and negatively impacts on erectile and ejaculatory function, which all lead to a reduction in fecundity [54].

**60**

(**Figure 1**).

**Figure 1.**

*Hypothesis on how epigenetic changes and impact of ROS due to an obese proinflammatory environment can occur at multiple different points along the development of the sperm, resulting in altered fertility [47].*
