Friday, 23 March 2018

L-carnitine Partially Improves Metabolic Syndrome Symptoms but does not Reverse Perturbed Sperm Function or Infertility in High Fat Diet-Induced Obese Mice


In recent years, adverse effects of obesity on female reproduction and male fertility have received significant attention. In this study, we investigated infertility improvements following L-Carnitine treatment using a high-fat diet (HFD)-induced obesity mouse model. Five-week-old male mice were divided into a control diet (CTD) group, a HFD group, and a HFD with L-Carnitine supplementation (HFD+C) group that received L-Carnitine-supplemented water and a HFD. At 30 weeks of age, mating tests with female mice were conducted to investigate reproductive ability. Dissection was then performed to analyse organ weights, blood glucose and lipid levels, and sperm motility. HFD mice displayed increased body, liver, and visceral fat weights and blood glucose, blood lipid, and liver lipid levels compared with those of CTD mice. In addition, sperm motility was decreased, and female mouse pregnancies could not be confirmed. HFD+C mice displayed significantly decreased body, liver, and visceral fat mass and blood and liver lipid concentrations compared with those of HFD mice. Though fertility was observed in one out of five mice, no significant improvement in sperm motility or fertility was observed. These results suggest that L-Carnitine administration does not reverse male infertility in diet induced obesity but partially improves metabolic syndrome symptoms.

It is currently estimated that one out of every six married couples in Japan have undergone infertility treatment and testing, indicating that this is a social problem. Infertility is defined by the World Health Organization as “inability to achieve pregnancy after 12 months of unprotected sexual intercourse”. According to the National Fertility Survey of birth trends conducted by the National Association of Population and Social Security Research in 2002, 12.1% of Japanese married couples had experienced infertility testing and treatment. This figure increased to 18.2% in the 2015 Survey. Research has demonstrated that 41% of infertility cases can be traced to problems with the woman, 24% to problems with the man, 24% to problems with both partners, and 11% unknown. This indicates that nearly half of infertility cases can be traced to problems with the man. Biological disorders that cause infertility in women include fallopian tube disorders, anovulation, and cervical disorders and in men include hypo spermatogenesis, seminal duct obstruction, accessory organ disorders, and sexual dysfunction. Other factors related to infertility include lifestyle-related causes, such as alcoholic beverage consumption, smoking, stress, obesity, and excessive dieting. In Japan, obesity is defined as a body mass index (BMI) of 25 kg/m2 and above. According to the international standard established by the World Health Organization, a BMI of 25 kg/m2 and above is considered “overweight,” while a BMI of 30 kg/m2 and above is considered “obese”. Obesity is caused by energy intake habitually exceeding energy consumption. Currently, 2.1 billion people, or 29% of the world’s population, are overweight or obese, indicating that this is a global problem. In Japan, although the percentage of obese adult women is on the decline, the percentage of obese adult men increased to 29.5% in 2015 from 20.4% in 1987. 

When the data for people of reproductive age were examined by age group, 26.6% of men in their twenties, 30.3% of men in their thirties, and 36.5% of men in their forties were either overweight are obese. Studies investigating the correlation between obesity in women and infertility reported that obesity caused declines in fertility rate and made women more susceptible to menstrual disorders. Furthermore, these studies revealed that overweight women had lower ongoing pregnancy rates than women at their ideal weight. Investigation of the correlation between obesity in men and infertility revealed that obese men have fewer sperm, lower sperm motility, and a higher percentage of sperm with DNA fragmentation. The majority of these studies were clinical studies conducted in humans.

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