Abstract
BackgroundThe number of founding germ cells (FGCs) in mammals is of fundamental significance to the fidelity of gene transmission between generations, but estimates from various methods vary widely. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women.ResultsThe germline-development model derives from the assumption that oogonial proliferation in the embryonic stage starts with a founding cells at t = 0 and that the subsequent proliferation can be defined as a simple stochastic birth process. It follows that the population size X(t) at the end of germline expansion (around the 5th month of pregnancy in humans; t = 0.42 years) is a random variable with a negative binomial distribution. A formula based on the expectation and variance of this random variable yields a moment-based estimate of a that is insensitive to the progressive reduction in oocyte numbers due to their utilization and apoptosis at later stages of life. In addition, we describe an algorithm for computing the maximum likelihood estimation of the FGC population size (a), as well as the rates of oogonial division and loss to apoptosis. Utilizing both of these approaches to evaluate available oocyte-counting data, we have obtained an estimate of a = 2 – 3 for Homo sapiens.ConclusionThe estimated number of founding germ cells in humans corresponds well with values previously derived from chimerical or mosaic mouse data. These findings suggest that the large variation in oocyte numbers between individual women is consistent with a smaller founding germ cell population size than has been estimated by cytological analyses.
Highlights
Despite great strides in our understanding of the genetic regulation of germ cell determination in recent years [1], the size of the founding germ cell population in humans remains obscure
Using a stochastic model to reconstruct the germ-cell development in human females, we show that the large variance observed in counts of human oocytes is consistent with the initial origin of these cells from a much smaller founding germ cells (FGCs) population than is often assumed
Our estimated values of the founding germ cell number a (MLE a = 2, moment estimate a = 2.7) differ substantially from the estimates made in previous studies [2,3] that relied on cytochemical staining of embryonic material
Summary
Despite great strides in our understanding of the genetic regulation of germ cell determination in recent years [1], the size of the founding germ cell population in humans remains obscure Due to this uncertainty, it is difficult in a clinical environment to estimate the probability that a mutant allele known to be mosaic in the somatic tissues of a parent will be transmitted to offspring. Genetic analysis of artificially generated chimerical cellular populations in the mouse indicate that there are only 2 to 9 cells that contribute to the germ cell population [4,5,6,7,8,9,10] In this communication, we derive a new method that is applicable to both humans and laboratory animals. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women
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