Stress during early pregnancy is linked to reduced reproductive function in male offspring

Men whose mothers were exposed to stressful life events while they were in the first 18 weeks of pregnancy may have reduced sperm counts when they become adults, according to a study published using Raine Study data, in the journal Human Reproduction.

Research has shown that the first few months of pregnancy is when male reproductive organs are at their most vulnerable stage of development. This current study of 643 young men aged 20 found that those who were exposed to at least one stressful life event during early gestation (0-18 weeks) had worse sperm quality and lower testosterone concentrations than those who were not exposed, or who were exposed during later gestation, between 18-34 weeks.

The findings come from the Raine Study, a multi-generational study that recruited nearly 3000 women in their 18th week of pregnancy in the period between May 1989 and November 1991. The mothers completed questionnaires at 18 and 34 weeks’ gestation, and each survey included questions about stressful life events during the preceding four months of pregnancy. These events included death of a close relative or friend, separation or divorce or marital problems, problems with children, mother’s or partner’s involuntary job loss, money problems, pregnancy concerns, moving home or other problems.

A total of 2868 children (1454 boys) were born to 2804 mothers and were followed by the researchers, making this the first study to investigate prospectively the links between exposure to stressful life events in early and late gestation and male reproductive function in young adult men. When they reached 20 years old, up to 643 young men underwent a testicular ultrasound examination and provided semen and blood samples for analysis.

The researchers found that 63% of the men had been exposed to at least one stressful life event in early gestation, while fewer stressful life events occurred in late gestation. Those who were exposed to stressful life events in early gestation had lower total sperm counts, fewer sperm that could swim well and lower concentrations of testosterone than those exposed to no events. The researchers adjusted their analyses to take account of factors that could affect their calculations, such as the mothers’ body mass index, socio-economic status and whether or not the mothers had given birth previously.

The senior author of the study, Roger Hart, Professor of Reproductive Medicine at the University of Western Australia and medical director of the Fertility Specialists of Western Australia IVF unit, said: “We found that men who had been exposed to three or more stressful life events during early gestation had an average of 36% reduction in the number of sperm in their ejaculate, a 12% reduction in sperm motility and an 11% reduction in testosterone levels compared to those men who were not exposed to any stressful life event during that period.

“This suggests that maternal exposure to stressful life events during early pregnancy, a vulnerable period for the development of male reproductive organs, may have important life-long adverse effects on men’s fertility. This contrasts with the absence of any significant effect of exposure to maternal stressful life events in late gestation.”

In their Human Reproduction paper, the authors write: “These potential associations could provide important insight into the decline of total sperm count in Western men, which has been, apart from genetic and direct spermatogenic damage, largely unexplained.”

Prof Hart said that exposure to stressful life events during early pregnancy was unlikely to cause a man to be infertile by itself, but when added to other factors, it could contribute to an increased risk of infertility.

“Like most things in life, if exposure to stressful life events in early gestation is added to other things that are known to affect men’s fertility, it may contribute to an increased risk of male infertility. These other, predominantly lifestyle exposures include being overweight, central obesity, smoking, excessive alcohol intake, high blood pressure, high cholesterol, sugar, or fat levels in the blood, a varicocele in the scrotum, or possibly exposure to chemicals in the environment that interfere with natural hormones, both before birth and in adulthood,” he said.

The researchers point out that they have found only an association between stressful life events in early pregnancy and reduced sperm quality and testosterone concentrations in offspring, not that one definitely causes the other.

First author of the study, Dr Elvira Bräuner, a senior scientist in reproductive epidemiology at the Department of Growth and Reproduction, Rigshospitalet in Copenhagen, Denmark, said: “It is likely that women have always been exposed to stressful life events during pregnancy. However, the World Health Organization has described a general upward trend in stress over time. So, the additional effect of a stressful life event during pregnancy might be more pronounced in women who are already stressed.”

One of the main limitations of the study is that it was not possible to measure how stressful life events affected women’s experiences and their perceptions of stress, and their resilience in coping with such events.

Prof Hart said: “Our findings suggest that improved support for women, both before and during pregnancy, but particularly during the first trimester, may improve the reproductive health of their male offspring. Men should also be made aware that their general health is also related to testicular health, so they should try to be as healthy as possible to ensure that not only do they have the best chance of maintaining fertility, but also of remaining healthy in later life.

“To provide some perspective, the association between exposure to stressful life events and reduction in sperm counts was not as strong as the association between maternal smoking and subsequent sperm counts, as this was associated with a 50% reduction in sperm number.”

To read the full paper, visit https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/dez070/5499161

The Raine Study

Raine Study marks milestone with 500 research studies published

WA’s unique longitudinal health study, The Raine Study, has celebrated the publication of the 500th research study using its data.

The Raine Study is one of the most richly detailed prospective cohorts of pregnancy, childhood, adolescence and now early adulthood to be carried out anywhere in the world.

It was established in 1989 to determine how events during pregnancy and childhood influence health in later life and has tracked almost 3000 Western Australian children, their parents, their grandparents and now their own children during that time.

The 500th research article to come out of the Raine Study found significant relationships between events during pregnancy and adiposity (obesity) and depression in adulthood.

Scientific Director of the Raine Study, Professor Leon Straker, said the 500th published paper was the perfect example of the value of the data collected by the Raine Study.

“Researchers have been able to use data collected from during pregnancy – including lifestyle and physical health based data – to examine impact in later life.”

Emeritus Professor Lawrence Beilin from the University of Western Australia, a co-investigator on the study, said that with an increasing incidence of obesity and mental health disorders in young adults, the research helped in discovering some factors during pregnancy that may contribute.

“This piece of research has shown a strong relationship of maternal smoking and a low family income with obesity and depression at the age of 20,” he said.

Socio-economic factors also had an impact on BMI (Body Mass Index) and depression at age 20.

“The value of discoveries such as this is to guide strategies to help families improve their health and well-being throughout their lives,” said Professor Straker.

This latest research adds to a long list of key health discoveries to come out of the Raine Study, including:

  • Establishing the safety of ultrasounds and the standard for routine prenatal ultrasound scanning worldwide.
  • Identifying genes associated with lung function, birthweight, puberty and language development.
  • Finding that children who were breastfed for four months or longer had a healthier weight, had less asthma and allergies and less behavioural problems.
  • Finding that a better quality diet in adolescence is related to better school achievement and fewer behavioural problems.
  • Finding that low vitamin D levels put children and teenagers at an increased risk for both allergy and asthma, and this affects boys more than girls.
  • Finding that work absenteeism is a significant issue for young adults and is associated with spinal pain and mental ill-health.
  • Identifying trajectories of participation in sports across childhood and adolescence predict better physical health in adulthood.

Four generations of families are now involved in the Raine Study. According to Professor Straker the potential future impact of the study was huge with data collected on Grandparents (Generation 0), Parents (Generation 1), Children (Generation 2) and now Grandchildren (Generation 3) from the same family.

“The extensive data collected since 1989 through the Raine Study continues to assist in unravelling some of the complexities of health and disease over the life course,” he said.

 

Thanks to the Perth Now for covering this article.

Meet Claire: 28 year old follow-up appointment

We followed the amazing Claire on part 1 of her 28 year old follow-up appointment recently. The commitment of our participants is something very special and we hope this little glimpse into what happens in a follow-up appointment showcases their amazing efforts.

 

Professor John Newnham

Professor John Newnham

Professor John Newnham was one of our Founding Investigators and continues to be a huge advocate and supporter of the Raine Study. This beautiful video from the The University of Western Australia and Women and Infants Research Foundation explains how the study began and the huge impact it has: