Paternal epigenetic effects

Heritable epigenetic changes, or transgenerational effects, are the result of the fixation of epigenetic markers in the genome of gametes as a result of environmental impacts. To identify paternal effects, we test in the wild guinea pig (Cavia aperea) whether alterations of environmental conditions lead to changes in the methylation patterns in tissues of fathers and their male offspring.

Project details
Duration: 03/2011 - 12/2014
Third-party funded: yes
Involved Department(s): Dept Reproduction BiologyDept Evolutionary Ecology, Dept Evolutionary Genetics, Dept Reproduction Management, Field Research Station
Leibniz-IZW Project Leader(s): Katarina Jewgenow (Dept Reproduction Biology)
Leibniz-IZW Project Team:

Jörns Fickel, Alexandra Weyrich (all: Dept Evolutionary Genetics), Sylvia Ortmann, Stephan Karl (Dept Evolutionary Ecology), Frank Göritz (Dept Reproduction Management), Irina Kasprzak (Field Research Station)

Consortium Partner(s):

Berlin Center for Genomics in Biodiversity Research (BeGenDiv)

Current Funding Organisation: Leibniz Competition
Research Foci:
Understanding the environmental context


Epigenetic inheritance of adapted traits or “experiences” to the next generation is fundamental for long term adaptive memory to changing environmental condition and is most likely not restricted to maternal transmission. In this study, we aimed to investigate whether changes of environmental conditions cause an epigenetic programming not only in father animals but also in their male offspring. To study these so-called paternal effects of exogenous factors on a molecular level, we applied moderate heat treatment and reduction of nutritional compounds during spermatogenesis and used assisted reproduction methods to identify changes in DNA methylation and gene expression of the offspring. To identify basic mechanisms of paternal epigenetic inheritance in a natural setting, we chose a genetically heterogeneous species rather than inbred strains or cell cultures.

In our study we confirmed our hypothesis on paternal epigenetic effects. We showed that the paternal epigenetic pattern (DNA methylation) of the wild guinea pig was modified after both treatments, heat exposure and low protein diet; both in fathers and sons, indicating immediate and inherited epigenetic modifications. Differences in the gene activity (transcription) to changing environmental conditions could be shown for selected genes in tissue samples from naïve sons sired by exposed fathers. Further analyses are ongoing. Embryonic gene expression was independent of treatment but determined by sire (paternal effect). Cryopreservation of sperm cells caused changes in gene expression in in-vitro produced embryos. The further developmental impact on the offspring remains still unclear.

To our best knowledge this is the biggest study on epigenetic adaptations in a wild, genetically heterogeneous mammal and the first study on epigenetic effects after exposure to increased ambient temperatures. In context with other newly published studies on paternal epigenetic transmission, our results confirm the transgenerational inheritance through the male germ line as an adaptive response to changing environmental conditions, in addition to the maternal response.   

In addition to the field station, where the animals were kept, and BeGenDiv, four different departments were involved: Department Evolutionary Ecology supervised the establishment and maintenance of the captive breeding colony of guinea pigs at the field station, and performed the feeding experiments. Department Evolutionary Genetics performed the whole genome sequencing of wild guinea pig and the methylome analysis in different tissues of fathers and sons, and thereby established their expertise in epigenetic research. Department Reproduction Biology studied the mating behaviour, mating system and oestrus behaviour in the animals to obtain well-staged preimplantation embryos. They also performed the gene expression studies of early embryos, as well as all hormone analysis of serum and faecal samples. Department Reproduction Management performed the monitoring of foetal growth, sample collection and veterinary health care of the guinea pigs during the experiment.



Selected Publications

Hribal R, Ringleb J, Braun BC, Jewgenow K (2012): Capabilities and challenges of examination of gene expression in early cat embryos. Reprod Dom Anim 47, 147–151. doi:10.1111/rda.12081.

Hribal R, Jewgenow K, Ruebensam K, Günther A (2016): Blastocyst recovery and multifactorial gene expression analysis in the wild guinea pig (Cavia aperea). THERIOGENOLOGY 86, 1299-1307. doi:10.1016/j.theriogenology.2016.04.071.

Rübensam K, Hribal R, Jewgenow K, Guenther A (2015): Seasonally different reproductive investment in a medium sized rodent (Cavia aperea). THERIOGENOLOGY 84, 639-644. doi:10.1016/j.theriogenology.2015.04.023.

Schumann K, Guenther A, Göritz F, Jewgenow K (2014b): Characterization of fetal growth by repeated ultrasound measurements in the wild guinea pig (Cavia aperea), THERIOGENOLOGY 82, 490-494. doi:10.1016/j.theriogenology.2014.05.007.

Schumann K, Guenther A, Jewgenow K, Trillmich F (2014a): Animal housing and welfare: effects of housing conditions on body weight and cortisol in a medium sized rodent (Cavia aperea). J APPL ANIM WELF SCI 17, 111-124. doi:10.1080/10888705.2014.884407.

Weyrich A (2012): Preparation of genomic DNA from mammalian sperm. CURR PROTOC MOL BIOL, 2:2.13.1-3. doi:10.1002/0471142727.mb0213s98.

Weyrich A, Schüllermann T, Heeger F, Jeschek M, Mazzoni CJ, Chen W, Schumann K, Fickel J (2014): Whole genome sequencing and methylome analysis of the wild guinea pig. BMC GENOMICS 15, 1036. doi:10.1186/1471-2164-15-1036.

Weyrich A, Lenz D, Jeschek M, Chung TH, Rübensam K, Göritz F, Jewgenow, K, Fickel J (2015): Paternal intergenerational epigenetic response to heat exposure in male wild guinea pigs. MOL ECOL 25, 1729-1740. doi:10.1111/mec.13494.

Weyrich A, Benz S, Karl S, Jeschek M, Jewgenow K, Fickel J (2016): Paternal heat exposure causes DNA methylation and gene expression changes of Stat3 in wild guinea pig sons. ECOL EVOL 6, 2657-2666. doi:10.1002/ece3.1993.

Weyrich A, Jeschek M,Schrapers KT, Lenz D, Chung TH, Rübensam K, Yasar S, Schneemann M, Ortmann S, Jewgenow K, Fickel J (2018): Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs. ENVIRON EPIGENET 4, dvy011. doi:10.1093/eep/dvy011.