Sperm Differences in Obesity May Not Show Up on Fertility Tests

Marlene Busko

February 13, 2020

An analysis of sperm from men who were part of a couple whose partner was undergoing in-vitro fertilization (IVF) identified differences in samples between obese vs nonobese men. Specifically, there were differences in the amounts of 27 proteins contained in the sperm.

Importantly, all 10 men in these infertile couples (5 obese men and 5 nonobese men) had clinically normal semen, lead study author Taylor Pini, PhD, a postdoctoral scientist at the Colorado Center for Reproductive Medicine, Lone Tree, Colorado, stressed to Medscape Medical News.

That is, the men all had normal sperm concentration, motility, morphology, and DNA fragmentation, which indicates that "these changes in obese men with no overt andrological diagnosis…suggests that traditional clinical semen assessments fail to detect important biochemical changes in spermatozoa which may compromise fertility," the authors write.

Should More Emphasis Be Put on Obesity as Impacting Male Fertility?

The researchers identified 2034 sperm proteins, of which 24 were significantly less abundant and 3 were more abundant in the obese men than in the men with a healthy weight (P < .05 for both).

The sperm proteins that were less plentiful in the obese men are involved in oxidative stress, inflammation, protein translation, DNA damage repair, and sperm function, and those that were more plentiful are involved in oxidative stress.

"These results suggest that oxidative stress and inflammation are closely tied to reproductive dysfunction in obese men," the researchers conclude, suggesting that "these processes likely impact protein translation and folding during spermatogenesis, leading to poor sperm function and subfertility."

Pini noted that "a lot more emphasis has been placed on female as opposed to male obesity" in couples going for infertility work-up, "but I think it is worth considering on the male side as well."

"It would be worth counseling patients, especially in the very early stages of trying to conceive, that overall health and particularly things like obesity are really worth considering prior to conception," she emphasized.

The study was published online February 5 in the Journal of Assisted Reproduction and Genetics.

Infertile Couples, Men With Clinically Normal Sperm

An estimated 38% of men of reproductive age (20 to 59 years) in the United States have obesity (body mass index [BMI] 30 kg/m2), Pini and colleagues note.

However, it is unclear how obesity may affect male fertility on a molecular level.

Previous studies of sperm proteins in obese men either used a less sensitive method (two-dimensional difference gel electrophoresis), or the more sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) but with a very small sample (3 men) including men with diabetes or smokers.

Pini and colleagues identified 5 obese men (BMI ≥ 30 kg/m2) and 5 non-obese men (BMI ≤ 25 kg/m2) seen at their reproductive medicine center who had clinically normal semen and did not smoke or have diabetes.

They collected semen samples from the men on the day of the oocyte retrieval in the men's partners, and they used LC-MS/MS to determine the protein content of the sperm.

The control patients had a mean BMI of 24, and the obese patients had a mean BMI of 33. On average, the men in each group were 39 years old (range 33 to 46).

Obese and nonobese men had similar rates of average sperm concentration (88 x 106), total motility (62%), normal morphology (2.9%), and DNA fragmentation (3.3%).

Among the 27 proteins with altered abundance in obese vs normal-weight men, some were involved in oxidative stress (5), inflammation (2), protein translation (3), DNA damage repair (1), and sperm function (3).

The LC-MS/MS findings were confirmed for several proteins by qualitative immunofluorescence and a quantitative protein immunoassay.

"We have shown that obesity significantly impacts the human sperm proteome, potentially to the detriment of important spermatogenic processes and the function of mature spermatozoa," the researchers report.

"These changes may be both symptoms of, and contributors to, the inflammation and oxidative stress associated with obesity, and may help to explain why obese men may have altered semen parameters, potentially leading to altered fertility."

"While some of the problems created by paternal obesity may be overcome by assisted reproduction techniques, the swath of implications following fertilization remains to be rigorously investigated," they note.

The authors conclude the study by writing that efforts should be directed toward the implementation of treatments to correct or limit the observed changes "when weight loss prior to conception is neither practical nor realistic."

The study was funded the Colorado Center for Reproductive Medicine. The authors have disclosed no relevant financial relationships.  

J Assist Reprod Genet. Published online February 5, 2020. Abstract

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