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Gonadal function in male mice altered by prenatal risk factors

Researchers have consistently shown that prenatal exposure to di(2-ethylhexyl) phthalate damages the reproductive system in male mice and causes fertility defects. In a new study, scientists at the University of Illinois Urbana-Champaign have shown that the combination of DEHP and a high-fat diet in pregnant mice can cause more harm to the offspring than each factor alone.

Male reproductive disorders are a growing problem due to global declines in sperm count and quality. Worryingly, chemicals such as DEHP, which can be found in food storage containers, pharmaceuticals and building materials, have been found to be one of the contributing factors. The toxicity of DEHP is due to its ability to mimic our body’s hormones, resulting in long-term health effects.

“The scientific community is aware of the fact that the current generation of men produces half as much sperm as the previous generation,” said CheMyong Jay Ko (EIRH), professor of veterinary medicine. “Although it is shocking, there is not much attention paid to understanding the causes.”

The researchers used Barker’s hypothesis as the guiding principle of their study. Proposed by British physician and epidemiologist David Barker, the hypothesis held that the nine months in the womb are one of the most critical periods in a person’s life and can shape their future health trajectories.

“Barker’s hypothesis focuses primarily on nutrition and we wanted to test whether the mother’s diet could change the health of the next generation,” Ko said. “In addition, unlike the previous generation, we are constantly exposed to chemicals such as “We wanted to ask if exposure to both factors can cause growing babies to have less functioning reproductive systems.”

In the past, both the Ko lab and other research groups have shown that prenatal exposure to DEHP decreases testosterone levels and causes fertility defects in male mice. Additionally, scientists have shown that a high-fat maternal diet can also decrease sperm count in male offspring. However, the effects of both had not been studied together.

The researchers used four groups of pregnant mice; one was a control and the other three were exposed to DEHP, a high-fat diet, or a combination of both. They then followed each litter, which contained an average of 6 male and 6 female pups.

“Surprisingly, we found that a high-fat diet had a more damaging effect on male reproductive systems compared to DEHP alone and puppies born to mothers who had been treated with both had the worst outcomes,” Ko said.

The researchers measured the weight of the body and different reproductive organs in puppies during different stages of growth and puberty. They found that although the body weight of puppies born to mothers on a high-fat diet alone or in combination with DEHP was higher than that of the other puppies, the weight of the reproductive organs was lower. They also found that these mice produced less sperm and had lower levels of testosterone. By staining the tissues, the researchers discovered that the reproductive organs had abnormal cells that contributed to gonadal dysfunction.

“In our studies we used these mice as a model. Although we need to confirm these results in humans, this study should serve as a warning to our generation that we should be careful with our environment and diet during pregnancy,” Ko said.

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