RESEARCH

Home | Research | News | People | Publications | Disclaimer | Contact | Cooperation | Neurootological Team

 

Perinatal development of physiological Control systems and of epigenetic adaptation processes

 

Field of research

Prenatal and early postnatal development of body functions and epigenetic adaptation processes in birds

The knowledge of the development of the body functions during embryogenesis as well as post hatching is a prerequisite to determine any environmental manipulations during incubation. Investigations carried out in our laboratory pioneered on the development of the thermoregulatory as well as the related systems (e.g. metabolism, cardiovascular system and respiration) in the Muscovy duck and other precocial bird species like the chicken and turkey. The investigations were focused on peripheral (autonomic mechanisms, related to heat production, body temperature, heat loss mechanisms andas well behavioural mechanisms in relation to preferred ambient temperature: Nichelmann et al., 1998, Tzschentke and Nichelmann, 1999, Nichelmann and Tzschentke, 2002, 2003, Janke et al., 2002)*. The other core aspect of our research is on the central nervous thermoregulatory mechanisms (neuronal hypothalamic thermosensitivity: Tzschentke and Basta, 2000, Tzschentke et al., 2000, Yakimova et al., 2005, Janke et al., 2005)*. Interestingly, our previous work on the development of neuronal hypothalamic thermosensitivity has shown that the electrophysiological characteristics (e.g., proportion of thermosensitive and -insensitive neurons, influence of the neuropeptide bombesin or GABA agonist) are very similar to those observed in mammals (Tzschentke and Basta, 2000, Tzschentke et al., 2000, Yakimova et al., 2005, Janke et al., 2005)*.

Plasticity of neuronal as well as peripheral termoregulatory mechanisms were investigated in relation to age and after acute and chronic environmental influences, mainly the influence of ambient temperature during incubation or postnatal development. Further, the influence of genetic selection on embryonic development of different chicken lines was examined (Janke et al., 2004)*.

 

General rules for development of physiological control systems

From the results of our investigations and from the related scientific literature, we postulated general rules for the development of physiological control systems, which seem to be relevant for birds as well as mammals (Nichelmann et al., 1999, 2001, Tzschentke and Basta, 2002, Tzschentke et al., 2004)*:

- The activity of organ functions occur during embryonic development even before the function is necessary for the immediate survival of the organism and may have a training effect on its postnatal efficiency.

- During early ontogeny most body functions start with uncoordinated and immediate (proximate) non-adaptive reactions on different endogenous and exogenous influences. This reaction pattern seems to be characteristic for critical (sensitive) phases during early ontogeny.

- During critical (sensitive) developmental phases, a long-term adaptation to an actual environment occurs via epigenetic adaptation processes.

 

Basic model of induction of epigenetic adaptation processes

We developed a basic model of induction of epigenetic adaptation processes, focused on epigenetic temperature adaptation using the bird embryo. This model is based on the fundamental idea by Dörner (1974: Acta biol. med. Germ., 33, 129-148) that in the course of perinatal life, most of the functional systems of an organism develop from linear open-loop-systems without feedback control into closed-control-systems with feedback. During critical phases, the actual control level at which the physiological parameters are regulated may determine the ‘set-point’ of the respective physiological control system during the entire life period. The determination of the ‘set-point’ depends on the endogenous and exogenous environment of the embryo/fetus. We postulate that ‘Epigenetic adaptation’ occurs during critical developmental phases and induces longlasting changes in the expression of related effector genes (Fig. 1). There is compelling evidence that many of the diseases of adult life including behavioural disorders have a part of their origin within the prenatal period and might be based on epigenetic mechanisms (fetal origin of adult diseases).

Fig. 1 Induction of epigenetic temperature adaptation

 

Epigenetic temperature adaptation

Epigenetic adaptation mechanisms might be used to adapt the organism, for instance, to the postnatal climatic conditions. In the bird embryo epigenetic temperature adaptation can be easily achieved by changes in the incubation environment, like incubation temperature, during the critical developmental phase, which occurs e.g. in the Muscovy duck at the end of incubation (Loh et al., 2004)*. Our investigations have shown that prenatal temperature experiences induce postnatal warm or cold adaptation. Changes related to the respective temperature adaptation were found in the periphery (autonomic and behavioural thermoregulatory mechanisms; Tzschentke and Nichelmann, 1997)* and in the brain (thermosensitivity of hypothalamic neurons; Tzschentke and Basta, 2002, Tzschentke et al., 2004)*. Prenatal temperature experiences, for instance, have a strong influence on postnatal neuronal hypothalamic thermosensitivity: e.g., on the 10th day post-hatching prenatal cold load elevated the neuronal hypothalamic warm-sensitivity by an increased proportion of warm- and a reduced proportion of cold-sensitive neurons in comparison with the control group. Prenatal warm load induced the opposite effect (Tzschentke and Basta, 2002, Tzschentke et al., 2004)*. During the first days of life (day 1 to day 5) changes in incubation temperature also induced a clear alteration of hypothalamic thermosensitivity, but this alteration was independent of the direction of change in incubation temperature (increase or decrease from the normal level; Tzschentke and Basta, 2002, Tzschentke et al., 2004)*. These proximate nonadaptive reactions of physiological mechanisms on endogenous or exogenous influences seem to be characteristic for critical (sensitive) phases during early ontogeny.

 

The bird embryo as model for investigations on epigenetic prenatal malprogramming in human medicine

Perinatal malprogramming occurs when epigenetic effectors are present in non-physiological concentrations during critical developmental periods (Tzschentke and Plagemann, 2006)*. In mammals including man gestational diabetes as well as early postnatal overfeeding, leading to perinatal hyperinsulinism, may result in increased later risk of becoming overweight and developing diabetes and alterations typical for the Metabolic Syndrome, a cluster of adipogenic, diabetogenic, and cardiovascular risk factors. Elevated insulin and leptin concentrations during 'critical periods' of neuronal development may cause a malprogramming of the neuropeptidergic systems of central nervous regulatory areas of body weight and metabolism, especially in the hypothalamus (Plagemann, 2004: Journal of Perinatal Medicine 32: 297-305). Similarity in the cascade of events between humans and chickens, leading to obesity, endorse the chicken embryo as well as the growing chicken as a unique model for investigation of the mechanisms related to the epigenetic prenatal malprogramming of the metabolism, which are involved in the genesis of obesity during later development.

 

* Complete quotation of own literature, included in the list of publications.

 

Current investigations

The working group Perinatal Adaptation actually investigates basic and applied aspects of early development and epigenetic adaptation of physiological functions.

Basic investigations

(1) Investigation of the mechanisms related to epigenetic prenatal 'malprogramming' of the metabolism using the bird embryo as a model (in co-operation with the working group "Experimental Obstetrics", Prof. Andreas Plagemann, and the Clinic of Obstetrics, Prof. Joachim Dudenhausen, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum).

(2) Investigations on early development of the thermoregulatory system and metabolism in birds with special focus on the characterisation of critical developmental phases

(3) Investigations on neuronal hypothalamic mechanisms involved in thermoregulation

- prenatal brain development in the Muscovy duck and in chicken: investigations on the impact of temperature stimulation on the development of neuronal hypothalamic NO-sythase activity in Muscovy duck (in cooperation with Dr. Valery I. Dunai, Department of Psychophysiology, Humanistic Faculty of the Belorussian State University , Minsk , Belarus)

- development of neuronal hypothalamic thermosensitivity in chicken embryos and growing chicks, concentrated on the characterisation of the high neuronal hypothalamic cold sensitivity

Role of GABAagonists and antagonists (in cooperation with Prof. Dr. Krassimira S. Yakimova, Dept. of Pharmacology, Faculty of Medicine, Medical University Sofia, Bulgaria)


-investigations of epigenetic temperature adaptation on peripheral and central nervous mechanisms with special attention on the long term effect of epigenetic adapation processes using c-Fos expression of hypothalamic neurons

(4) Investigations on neuronal plasticity of the auditory system (in cooperation with Dr. Dietmar Basta (Neurootological team), ENT at UKB, Free University of Berlin)

-Cochlear-Implantation-Research (Guinea pig)

-Influence of intracochlear, electrical stimulation on cellular mechanisms in the central auditory pathway

 

Applied investigations

The incubation climate has a great impact on the later development and performance in poultry. To optimise incubation conditions, knowledge on the physiological needs of the embryos is necessary. These critical applications happen to be the need of the hour. An as such, in co-operation with different partners from poultry industry we perform investigations on development of physiological parameters (heat production, body temperature) of the embryos of modern high yield species(in co-operation with PasReform Hatchery Technology , The NL, Dr. Marleen Boerjan).

Other topics are investigations on the impact of manipulations of incubation temperature on post-hatching performance in growing broiler chicks (in co-operation with FLI, Friedrich-Loeffler-Institute, Institute of Animal Nutrition, PD Dr. Ingrid Halle).

 

Current projects

2007-2013: The bird embryo as model for investigations on epigenetic prenatal malprogramming, with gestational diabetes by way of example (DFG: TZ 6/17-1). This project is a co-operation between the working group "Experimental Obstetrics" (Prof. Andreas Plagemann, PL 241/6-1) and the Clinic of Obstetrics (Prof. Joachim Dudenhausen) of the Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum.

since 2005: Importance of incubation temperature for the development of the central NO-ergic system in Muscovy duck embryos (in cooperation with Dr. Valery I. Dunai, Department of Human Ecology, Belorussian State University, Minsk, Belarus)(DFG: 436 WER 17/3/05; 436 WER 17/5/06)

 

Former projects

2004-2006: Thermic induced c-fos expression in the preoptic area of the anterior hypothalamus in chicken incubated at different temperatures (DFG: JA 1440/1-1)

2004-2005: Modulatory influence of GABAa and GABAb antagonists on neuronal thermosensitivity of the anterior hypothalamus of juvenile chicken (in cooperation with Prof. Krassimira S. Yakimova, Deptm. of Pharmacology, Faculty of Medicine, Medical University Sofia, Bulgaria)(DAAD 2004; DFG: 436 BUL 17/5/05)

2004: Development of the central NO-ergic system in Muscovy duck embryos (in co-operation with Dr. Valery I. Dunai, The Interdisciplinary Co-ordinating Center Medic-Psychological and Chemic-Pharmaceutical Technologies, Belorussian State University, Minsk, Belarus)(DFG: 436 WER 17/7/04)

2003: Chick incubation (in co-operation with Dr. M.L. Boerjan, R&D department, PasReform Hatchery Technologies, Zeddam, The Netherlands)

2001-2003: Epigenetics (DFG: TZ 6/10)

2000-2004: Development of endothermy in bird embryos (DFG: TZ 6/6-4)

2000-2005: Influence of prenatal temperature load on postnatal neuronal hypothalamic thermosensitivity in birds (DFG: TZ 6/2-2)

1997: Development of endothermy in bird embryos (DFG: Bu 1047/1-1)

1995-1998: Influence of prenatal temperature load on postnatal neuronal hypothalamic thermosensitivity in birds (DFG: TZ 6/2-1)

1994-1997: Development of endothermy in bird embryos (in co-operation with Prof. Dr. Heike Tönhardt, Working Group Perinatal Development, Institute of Veterinary Physiology, Faculty of Veterinary Medicine, Free University of Berlin)(DFG: Ni 336/3-1 and To 181/1-1)