Meiotic progression in human testis

Balanced reciprocal translocations, recTr, are the most common structural chromosome abnormalities found in the general populations. The reciprocal translocations themselves have been thought to be genetically inactive but could result in the outcome of miscarriage or inborn abnormalities when its meiotic segregants (products of its adjacent segregation or 3:1 segregation) are inherited by offspring. In this respect, the induction of translocations in germ cells called attention to the hereditary effects of radiation. The induction of translocations by radiation in spermatogonial stem cells has been extensively studied in the experimental animals (Translocations in spermatogonia, mousae and other mammals). In spite of the experimental evidence accumulated in various mammalian species including man, the inheritance of translocations has not been confirmed in the offspring of Atomic bomb survivors in Hiroshima and Nagasaki. The enigma has not been solved.
Recently, evidence has been accumulated to show that large fraction of de novo translocations, newly formed but not inherited, translocations are accumulated in the infertile men who are diagnosed to suffer from azoosperma and oligospermia (Infertile men, and also recent reviews by Mau-Holzmann, 2005; Madan, 2012; Godo et al., 2013; Zhang et al., 2015).

 The above figure is a summary of the meiotic progression in 8 infertile men with azoospermia or oligospermia. In the carriers of de novo recTr, the meiotic progression from spermatogonia/pachytene to metaphase I, M-I, is severely suppressed and the suppresstion is further evident for stage from M-I to M-II. However, when the translocation is inherited from his parent, the suppressive effects are minimal. For the Robertsonian translocations of de novo origin, progress towards M-I is not suppressed but progression from M-I to M-II is suppressed.
The suppression of meiotic progression by reciprocal translocation of de novo origin has been implicate for the humped dose-response curves of radiation-induced spermatogonial translocations, and reduced transmission of radiation-induced translocations to the offspring of A-bomb survivors (Sasaki, 2006).

     In the F1 children bone to the exposed parent, non-Robertsonian structural aberrations are found in 0.16 % of the exposed parents, which is comparable to that in the newborn infants (0.14 % of world total and 0.10 % in Japanese children) in general populations and lower than that in the internal controls (unexposed, 0.26%). Since parental origin of these chromosome aberrations has not been fully determined, the contribution of the radiation dose cannot be assessed with any certainty (see, A-bomb F1 study).
     On the other hand, the sex chromosome aneuploidies are all de novo mutations. However, in the experimental animals including Drosophila, aneuploidy has been generally accepted to have no relation to the radiation dose. Indeed, the frequencies of sex chromosome aneuploidy are very comparable among newborns in general populations, children bone to exposed and unexposed parents. Simple dose response for absolute frequencies shows the dose-response with minimum doubling dose of about D_w=0.28 Sv. However, the relative risk is dose independent, that is D_w=∞. Another point is that the aneuploidy is also dependent on the maternal age. Thus, the doubling dose should be treated with caution. With these modifying factors in considerations, Neel et al. (1990) concluded that the exposuer did not produce and increase in aneuplidy in this population. 

Parental gonadal dose (Sv) No. of Sex chromosome aneuploidy Range Mean children No. (%) 0 0 8,225 24 0.292 .0001-0.050 0.024 1,346 0 0 0.051-0.100 0.073 951 2 0.210 0.010-0.500 0.263 2,693 9 0.334 0.501-1.000 0.719 1,531 3 0.196 1.001-1.500 1.227 686 2 0.292 1.501-2.000 1.716 295 1 0.339 2.001-2.500 2.228 157 0 0 ≥2.501 3.674 331 2 0.604 Average gonadal dose is 0.603 Sv (DS86 dosimetry system, in which neutrons are weighted by RBE=20) Neel, J. V., Schull, W. J., Awa, A. A., Satoh, C., Kato, H., Otake, M. and Yoshimoto, Y. (1990): The children of parents exposed to atomic bombs: estimates of the genetic doubling dose of radiation for humans. Am. J. Hum. Genet., 46:1053-1072.