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Projects / Programmes source: ARIS

Psychological and reproductive disturbances in men exposed to prenatal stress.

Research activity

Code Science Field Subfield
3.05.00  Medical sciences  Human reproduction   

Code Science Field
B007  Biomedical sciences  Medicine (human and vertebrates) 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
Stress, mood disorders, aggression, reproduction, sex behavior, human, mouse, epigenetics
Evaluation (rules)
source: COBISS
Researchers (15)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  12218  PhD Metoda Dodič Fikfak  Public health (occupational safety)  Researcher  2014 - 2017  1,227 
2.  34821  Barbara Dolenc  Psychology  Researcher  2014  78 
3.  10568  Sašo Drobnič  Human reproduction  Researcher  2014 - 2017  137 
4.  32106  PhD Barbara Golob  Human reproduction  Researcher  2014 - 2015  18 
5.  33384  MSc Žiga Jan  Human reproduction  Researcher  2014 - 2015  16 
6.  03721  Mojca Kolbezen Simoniti  Public health (occupational safety)  Researcher  2014 - 2017  43 
7.  13330  PhD Gregor Majdič  Veterinarian medicine  Researcher  2014 - 2017  576 
8.  22159  Martina Pečlin    Technical associate  2014 - 2017 
9.  37781  PhD Urška Smrke  Psychology  Researcher  2015 - 2016  91 
10.  29351  PhD Tanja Španić  Veterinarian medicine  Researcher  2014 - 2016  42 
11.  15883  PhD Lilijana Šprah  Psychology  Researcher  2014 - 2017  494 
12.  34286  Nina Šterman    Technical associate  2014 - 2015 
13.  19487  PhD Malan Štrbenc  Veterinarian medicine  Researcher  2016 - 2017  87 
14.  05015  PhD Ivan Verdenik  Human reproduction  Researcher  2014 - 2017  479 
15.  19449  PhD Branko Zorn  Human reproduction  Head  2014 - 2017  307 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  76,311 
2.  0406  University of Ljubljana, Veterinary Faculty  Ljubljana  1627139  10,689 
3.  0618  Research Centre of the Slovenian Academy of Sciences and Arts  Ljubljana  5105498000  62,500 
Abstract
Studies have shown that prenatal stress has profound effects on fetal development and could have long lasting consequences for health. Most often reported defects in adult life are increased risk for cardiovascular disease, obesity and permanent changes in brain neurotransmitter system, what could cause increased vulnerability for mental disorders such as mood disorders (depression, anxiety), schizophrenia, increased abuse of psychoactive substances, behavioural disorders and sleep disturbances. Some studies have also shown that prenatal stress could affect reproductive function in adult offspring of mothers, stressed during pregnancy however, these mechanisms are still very unclear. In the proposed project we will examine influence of prenatal stress on basic mechanisms of development of male reproductive system and male typical behavioural patterns in laboratory mice; vulnerability for development of mood disorders and aggressive behavioural patterns in young adult males; reproductive function, fertility and hormone levels in young adult males. Pregnant female mice will be exposed to stress and male offspring of these mice will be tested for male sexual behaviour and intermale aggression. Mice will be sacrificed and testes, brains and blood for hormonal measurements will be collected. Several prenatally stressed males will be mated with normal females to determine, if any of the observed effects are transferred transgenerationally into the next generations. In the second part, we will examine if similar mechanisms operate in humans. In June 1991, during the separation of Slovenia from Yugoslavia, 10 days long war broke out and was undoubtedly very stressful event for citizens of Slovenia. A sample of study participants will be composed from the general population of persons, born in 1991 and 1992. Male volunteers will be divided into 4 groups (N=400) in regard to their exposure to prenatal stress at different time periods (first, second and third trimester and control group, conceived after the war in Slovenia). Participants will within the psychological phase of study complete a set of psychodiagnostic questionnaires and also introduced with the possibility to participate in the andrologic phase of the study where their samples of semen and blood will be collected in order to perform astandard semen analyses and hormone tests (together 120-200 participants). The psychological profile of participants will be created which will enable to assess the vulnerability for some mood disorders (depression, anxiety, bipolar disorder), expression of aggressive behavioural patterns (physical and/or verbal aggression, anger, hostility) and the severity of symptoms associated with depression or anxiety (depression, anxiety, loss of interests, physical, mental or cognitive tiredness). After completing the andrological part of the study, we will carry out a correlation analysis between psychological profiles and general andrologic parameters (sperm count, motility and normal morphology) and levels of reproductive and stress hormones. All collected data will be subjected to the appropriate statistical analyses to determine any significant long lasting effects of prenatal stress during the 10 days war on fetal development and health status of male offspring. Results: Our proposed study will be the first study to show clearly if there is a connection between different forms of prenatal stress and male reproductive function in adulthood. Moreover, this will be one of very rare studies where a psychological profile of participants will be designed in order to identify a possible association between prenatal stress and vulnerability towards mood disorders and aggressive behavioural patterns.
Significance for science
Stress is a major problem in developed countries. Direct influences of stress for health are relatively well studied and understood also in humans. Much less is known about long term effects, in particularly about effects of prenatal stress for human health. Some studies in recent years have shown a likely connection between exposure to stress in developing fetus and development of certain psychiatric disorders in adulthood, although the mechanisms causing such problems are not yet well understood. Such studies in humans are very challenging as it is difficult to find larger groups of pregnant mothers that were exposed to similar stressors in well-defined time periods, and then following their offspring up to adult life. In Slovenia, there was a short military conflict in 1991 that undoubtedly presented a major stress for citizens of Slovenia, including mothers that were pregnant in this period. Their offspring therefore represents an excellent, yet unstudied model about long-term effects of prenatal stress. Results of the project are important for understanding consequences and mechanisms of prenatal stress. Our study is one of very few such studies in the world that enable examination of possible health effects of prenatal stress in well-defined times during different periods of pregnancy. Beside possible effects for mental health, we as well examined a reproductive function of male volunteers participating in the study as some studies in laboratory animals have shown, that prenatal stress could influence reproductive health and fertility in animals, exposed to stress through their mothers. As far as we know, no such study has been performed in humans before. Therefore, the results of the this study are very important for establishing if prenatal stress in humans could affect male reproductive health and could have important consequences for understanding male fertility and subfertility, which is increasing in recent decades in developed countries.
Significance for the country
Mental health disorders connected with stress are a large burden for societies due to large direct costs of health management of such people and due to lost working abilities of affected patients. Furthermore, mental health disorders and changes in lifestyle due to such disorders could lead to other health problems such as coronary hearth disease and obesity, and consequently diabetes. Infertility has also large indirect effects on the society and public health systems, and such problems could also be an underlying cause for some mental health problems such as depression. Understanding the mechanisms that are underlying cause of such health problems would lead to better treatments and prevention of patients, what would have large benefits for hole societies both through lower healthcare costs and higher working abilities of the populations in their working age. Results of the study were included in the lectures to undergraduate and postgraduate students as all three main collaborators on the project are also lecturers at the University and did present the results to the students. Furthermore, as this is the first such study examining male reproductive effects of prenatal stress and for the first time uses unique and very informative human population, it could have an important international implications and will therefore also contribute to the promotion of Slovenia and Slovenian science. Already during the project we informed the general public about the project and importanc of stress through various publications in popular magazines and newspapers, as well as in radio and television shows, where all three project PIs were guests (Lilijana Šprah, Branko Zorn and Gregor Majdič). This helped us to raise awareness of the harmful effects of stress among the general population. We also informed the public about the project via social networks (Facebook), and included research results into the teaching of students by the project leaders. This has raised the awareness of the long-term adverse effects of stress in Slovenia both between the general public and the professional public.
Most important scientific results Annual report 2014, 2015, final report
Most important socioeconomically and culturally relevant results Final report
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