Institute Cytology and Genetics

Laboratory of Endocrine Genetics

Head A.V.Osadchuk, Ph.D.

A comparison of coordinated Leydig cell responsiveness values predicted on the basis of the 4-locus model with the values observed for 36 phenotypes in diallel crosses of 6 inbred mice lines

Effect of selection for domestic behavior on the in vitro basal adrenal production of cortisol in silver fox fetuses aged from 35 to 50 days of fetal life.

Values are mean SEM. Asterisks designate significant differences (P at least < 0.05) between domesticated and control groups. - females, - males

The major direction of research at the Laboratory is toward the study of the genetic and phenogenetic control of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal systems, the clarification of the genetic-endocrinological and ethological mechanisms of differential reproduction.

Using a series of inbred mouse strains, studies on the genetic-evolutionary aspects and genetic control of the hypothalamic-pituitary-testicular axis were performed.

1. Genotype-dependent variability in plasma testosterone and corticosterone in aggressive and sexual interactions between mice was found for 13 inbred strains. Based on the hierarchical tree cluster analysis of the strain diversity, 6 clusters (branches) of inbred mouse strains were detected.

2. Positive between strain correlations between plasma testosterone, reproductive success and social dominance level were demonstrated for experimental micropopulations of 6 inbred mouse strains contrasting in the above hormonal activities and allowing the paternity determination using genetic markers. This provided evidence for the adaptive significance of the revealed hormonal testicular variations.

3. Based on the phenogenetic analysis at the levels of the organism, organ and cells, it was demonstrated that the between 6 strain variability for the hormonal activity of Leydig cells is the main cause of the between strain differences in the reactivity of the pituitary-testicular axis.

4. In turn, the strain-related differences in the hormonal activity of Leydig cells were determined by the correlative between strain variability in cAMP- and substrate-dependent testosterone production by Leydig cells based on the coordinated between strain differences in the key microsomal steroidogenic enzyme activities.

5. Finally, diallel genetic analysis of the cAMP- and substrate-dependent testosterone production by Leydig cells in 6 inbred mouse strains and their F1 reciprocal hybrids demonstrated their coordinated and concomitantly polygenic genetic control. Specifically, phenotypic variations in testosterone production were significantly determined by the following components: interstrain effects, general and specific combining ability effects, residual reciprocal effects and mean directional dominance. With the discriminant and multiple regression analysis as a basis, a four-locus genetic model accounting for more than 90% of the genotype-dependent variation was developed. One or two of the loci are linked to the sex chromosomes and the rest are linked to the autosomes. Three of the loci manifest epistatic digenic interactions. The fourth autosomal locus has only additive and dominance effects. Thus, the present study established for the first time the existence of a 4-locus genetic system controlling the coordinated Leydig cell responsiveness. The developed genetic model is a good tool for molecular-genetic analysis of testicular steroidogenesis. The inference regarding the coordinated Leydig cell responsiveness inheritance pattern may concern other mammalian species, man, too. This appears a reasonable extension because relying on genes with relatively mild action not causing impairment of the reproductive function and sterility and, consequently, widespread in natural populations.

The role of human-animal interactions in the hormonal control of reproductive processes was studied in two species of the Canidae family. The effect of stress caused by human contacts on hormonal parameters, fertility and embryo viability, was studied in pregnant blue foxes (Alopex lagopus), as well as on the fetal and postnatal development of the pituitary-gonadal and pituitary-adrenal systems in their offspring. These studies were conducted in collaboration with the Norway Agricultural University. To establish the genetic and physiological mechanisms of the early evolution of domestic animals, a model of silver fox domestication was developed at this Institute by long-term selection for lack of aggression and fear towards human (domestic behaviour). Using this model, we demonstrated changes in the gonadal function of domesticated foxes. Our study showed timing shift of the annual rhythm of ovarian activity and a depressed relationship between photoperiod and endogenous hormonal cycles in domesticated vixens. These animals were also more resistant to the delerevious effects of the artificial photoperiods on hormonal secretion and fertility. Shorter period of testicular activity, lower sperm production and lower sexual activity were found in domesticated males. Behavioral selection also reduced sexual and increased agonistic behavior in males during bisexual encounters. Study on fetal development in domesticated animals indicated heterochrony in the pituitary-testicular axis. As a result, the consequences of relatively short- and long-term human-animal relations on the endocrine control of reproduction in farmed silver and blue foxes were identified.