Three-generation Investigation on Serotonin Content in Rat Immune Cells long after β-endorphin Exposure in Late Pregnancy

Abstract

Female rats were treated with beta-endorphin on the 19th day of pregnancy. Serotonin content of immune cells (peritoneal lymphocytes, monocyte-macrophage-granulocyte group (mo-gran), mast cells, blood lymphocytes, granulocytes and monocytes, thymus lymphocytes) were studied in the mothers (P-generation four weeks after delivery), in the male offspring (F1) generation (at seven weeks), in the female offspring (four weeks after their own delivery) and in their offspring (F2 generation, at seven weeks). P-mother cells' serotonin content was not influenced by endorphin treatment, while F1 generation's mo-gran and blood lymphocyte serotonin content was reduced (in contrast, histamine content of mo-gran increased). Four weeks after delivery, an increase in serotonin content was observed in the F1 generation in the peritoneal lymphocytes and mast cells as well as in blood lymphocytes. In contrast, serotonin content was reduced in blood granulocytes and monocytes. In the F2 (grandson) generation, a reduction in mast cell serotonin content and sensitization of blood and thymic lymphocytes to repeated endorphin treatment was provoked. The significant changes were more expressed in the F2 generation compared to F1, also appearing earlier. The results unequivocally suggest that the increase in endorphin levels during late pregnancy can cause permanent changes in the F1 and F2 generations, which means that the imprinting effect can be transgenerationally transmitted.

Hormonal imprinting: phylogeny, ontogeny, diseases and possible role in present‐day human evolution

“…110 Recently the reduction of mast cell serotonin content in the grandson generation of rats that had been endorphin-treated during late pregnancy was observed. 111 These results pointed to the possibility of transgenerational human effects and there are now some intriguing observatons on this subject.…”

Effect of perinatal stress on the biogenic amine neurotransmitter level of the adult rat's brain

“…However, in this critical period molecules similar to the target hormone (related hormones, hormone analogues, synthetic chemicals, etc.) also can bind to the receptor, provoking a false imprinting, which causes life‐long disturbances in the receptor's binding capacity and other processes, e.g., hormone production and behavior (Csaba, 2008; Csaba and Inczefi‐Gonda, 1992; Nelson et al, 1994) and can be transmitted transgenerationally (Csaba, 1980, 1984, 2000, 2008; Csaba et al, 2005). It was also cleared that perinatal treatments with different molecules which can provoke hormonal imprinting and are in connection with brain‐produced neurotransmitters and pain regulation (e.g., beta endorphin or alcohol) can cause troubles in the production of them, for life (Csaba and Tekes, 2005; Csaba et al, 2003; Tekes et al, 2006; Tekes et al, 2007a,b).…”

Transgenerational Epigenetic Inheritance: Prevalence, Mechanisms, and Implications for the Study of Heredity and Evolution

“…However, this is a complex case that seems to involve epigenetic modifications in the A vy locus as well as in other loci in the genome (Blewitt et al 2006;Cropley et al 2006;Waterland et al 2007Waterland et al , 2008). Another case we included was that reported by Csaba et al (2005) in which the modified serotonin content induced in the immune cells of mice treated with endomorphin during pregnancy is subsequently transmitted to their grandchildren. We did not include the many cases of single generation inheritance, even though epigenetic inheritance seems quite plausible in some of them, as, for example, when a predisposition to cancer in humans is related to an epimutation (an epigenetic hereditary abnormality in gene expression) in a mismatch-repair gene, and this epimutation is transmitted from mother to son (Hitchins et al 2007).…”

“…On the other hand, when a male mammal is exposed to an inducer, two generations of transmission (from F 0 to F 2 ) are sufficient to establish that there has been epigenetic transmission through the germline rather than through direct induction. When the epigenetic effects (e.g., patterns of methylation) in the F 1 and F 2 generations are identical, and when Csaba et al (1999), Csaba andKovacs (1990, 1995), Csaba et al (1982a,b) Volvox carteri It seems that all ciliates show cortical inheritance and guided assembly of cortical structures (Frankel 1989). Ciliates have a silent micronucleus and an active macronucleus, from which noncoding sequences are excised and coding sequences are amplified.…”