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On sperm counts and bulging waistlines

Rujuta Vaidya

Obesity is an emerging health challenge in India, estimated to affect over 135 million individuals at present. Now, a new study from researchers at the National Institute for Research in Reproductive Health (NIRRH-ICMR) investigates the unexplored link between obesity and male fertility.

Adult lean(left) and obese(right) rats of same age
Adult lean(left) and obese(right) rats of same age   (Photo: Giridharan NV, Indian J Med Res. 2018 Nov; 148(5): 659–669)

Let’s admit it - we’ve all been disappointed when we couldn’t fit into that one favourite pair of jeans. Fret not, for you’re not alone! Obesity is shaping up to be a serious problem in both developed and developing countries, including India. Now, a new study from researchers at the National Institute for Research in Reproductive Health (NIRRH-ICMR) shows that both genetic- and diet-induced obesity can have a lasting effect on the process of sperm formation and male fertility.

Experts cite multiple reasons for our bulging waistlines, from junk food to stress to the lack of physical activity in our lifestyles. Obesity has been linked to several diseases including diabetes, blood pressure, osteoarthritis, sleep apnea, just to name a few. Along with these, the connection between obesity and infertility has been explored since as early as the 1950s. However, the mechanisms through which obesity affects male fertility remain largely unexplored.

Unsettled by this startling gap in knowledge, Nafisa Balasinor and Sharvari Deshpande from NIRRH embarked on a journey to find out how obesity would affect spermatogenesis in collaboration with National Centre for Laboratory Animal Sciences (NCLAS), National Institute of Nutrition (NIN), Hyderabad.

Looking through the reported studies that linked obesity and male infertility, Deshpande was surprised to notice the high degree of variability in the results. That is, even though all the patients selected for these studies were clinically obese, their hormone levels and reproductive abilities were affected to different extents. Profiles of sex hormones, such as testosterone, also differed in these affected individuals.

Interestingly, even in rodent systems for obesity, fertility was affected to variable extents; some rodents had defective sperm, some would be completely infertile, while some would show no effects. In order to understand the reasons behind this variability, Deshpande decided to use two separate rat models – a genetically inherited obesity model wherein rats were obese as a result of a mutation in Chromosome 5, and a diet-induced obesity model wherein rats were obese as a result of consuming a diet that was rich in lipids. As obesity depends on myriad factors like environment, ethnicity, diets, she hoped to simplify matters by studying these model systems.

Deshpande’s experiments revealed an intriguing finding – obesity was affecting cell division, specifically in the germ cells, at different stages in the two rat models.

During spermatogenesis, the genetically obese mice had low numbers of elongated spermatids, cells that are one step shy of becoming a sperm. As a result, the genetically obese rats formed less sperms and were therefore infertile. Diet-induced obese mice on the other hand, were low in round spermatids, cells at a stage prior to formation of elongated spermatids. Even though the number of sperms was unaffected in this group, these rats had higher instances of fetal death during or after implantation, and produced less progeny as compared to the controls.

‘Unlike most papers which took into account gross sperm parameters, we decided to go one step ahead. Our findings make a clear distinction in how genetics and diet can affect male fertility,’ says Deshpande, calling this the strongest point of their paper.

The researchers propose Adiposity Index, a measure of accumulated fat in the body, as the reason for these differences. The index was different for the genetically obese and diet induced obese rats, even though their total body weight was identical.

‘The comparison between genetically inherited - and diet-induced obese model systems are indeed interesting observations’, says Ullas Kolthur from the Tata Institute of Fundamental Research, Mumbai, who was not associated with this study. He suggested that exploring molecular mechanisms behind these observations would allow a better understanding of these effects.


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