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Seminal fluid key to offspring health

Father's seed The health of a male's seminal fluid can affect his fertility and how fat his adult offspring grows, a new study in mice has found.

If the same thing applies in humans, the study could help explain how obesity is transmitted between generations and may shed light health issues in IVF children, says Professor Sarah Robertson of the Robinson Institute at the University of Adelaide.

"The male is contributing a lot more than just the sperm that fertilises the egg," says Robertson.

While it is well known that a mother's diet, stress and level of infection can influence the health of offspring, recent evidence suggests fathers also play an important role.

Robertson and colleagues investigated one particular hypothesis; that the seminal fluid plays an important role in the development of metabolic disorders such as obesity and type 2 diabetes, in their offspring.

Apart from sperm, semen is mostly made up of seminal fluid, which comes from glands such as the prostate and seminal vesicles.

Robertson and colleagues looked at what happened when they operated on laboratory mice to remove their seminal vesicles.

Only a quarter of matings with females resulted in pregnancies, and each of these resulted in fewer offspring than normal.

"There was a major reduction in the male fertility," says Robertson.

Also, offspring from the seminal fluid-deficient males were smaller at birth, but after puberty grew much fatter than control mice.

"The offspring were on average 5 per cent larger than the controls," says Robertson. "The males were affected way more than the females."

"In male offspring, this was associated with a 72 per cent increase in abdominal fat, plus a 20 per cent increase in the size of individual fat cells."

The animals' hormone profile also showed they had a slower metabolism than controls. And they had higher blood pressure and reduced glucose tolerance &emdash; in humans, this is associated with the development of type 2 diabetes.

Researchers investigated 97 adult offspring from 22 pregnancies sired by seminal fluid- deficient males, and 132 offspring from 25 pregnancies in the controls.

Semen signals

When the researchers took a closer look they found that conception and the health of offspring was dependent on signals given by the seminal fluid to the reproductive tract of the females.

"If the seminal fluid is deficient it can't do that job," says Robertson.

The researchers discovered this during a complex set of experiments.

First they removed embryos from females who had been inseminated by a seminal fluid-deficient male.

"They grew much better in vitro suggesting there was something bad about the tract that we were releasing them from," says Robertson.

To test this hypothesis, the researchers transferred normal embryos, sired by normal males, into the same females, and found the development of these embryos was also affected.

"We could impart the adverse effect on the offspring simply be exposing them to the female tract," says Robertson.

The researchers discovered that healthy seminal fluid turned on growth factors that support the growth of the embryo and turn off those that are bad for it.

"The embryos have to get the right signals to grow in the right way," says Robertson.

Relevance to humans

Since the anatomy of mice and humans differs, Robertson says it is not possible to extrapolate the findings directly to humans.

However, there is already evidence showing factors such as smoking and infections influences a man's seminal fluid, and that seminal fluid influences gene expression of growth factors in some parts of the female reproductive tract.

If it turns out that similar things are happening in humans to mice, this could give new insight into how some of the obesity epidemic is being transmitted between generations in people, says Robertson.

And she says it may provide a way to improve IVF outcomes, as well as help explain health issues seen in some IVF children.

"There is some evidence that IVF children have slightly different metabolic health," says Robertson.

She says such children have a slightly lower birth weight, which often precedes metabolic dysfunction, and have differences in blood pressure and glucose tolerance, which may be signs of propensity to obesity and diabetes later in life.