The neonatal period: a critical interval in male primate development

Abstract

It appears from the evidence documented in this Commentary that the neonatal period is another critical stage in the process of sexual, behavioural and immune system development and maturation in primates. Interference with normal brain-pituitary-gonadal function during this period (e.g. with a GnRH analogue in monkeys) appears to impact adversely on subsequent reproductive, immunological and behavioural function. These data further emphasize the importance of fully understanding the regulatory mechanisms that govern neonatal gonadal function in the primate, if we are to eliminate, control or minimize the potential risk resulting from its disruption in humans. Given the recent evidence that the reproductive potential of the human male has declined rather dramatically over the last 50 years, and that clinical conditions associated with abnormal testicular function are on the rise, continued investigation in this area would appear to be imperative.

The neuroendocrine timing of puberty

“…It is highly likely that the episodic release of LH reflects pulsatile release of GnRH from the fetal hypothalamus; indeed pharmacological blockade of GnRH action in fetal lambs results in a substantial reduction in testicular volume in later life (Brooks et al 1995), evidence that activation of GnRH secretion early in life is important in testicular development. In male primates including humans there are periods of activation both in the fetal period and in the very early neonatal period (Plant 1985, Mann & Fraser 1996. These early periods of activation of the GnRH secretory system may be important for masculinisation of the brain, development of subsequent sexual behaviour, and control of Sertoli cell proliferation in the testis.…”

Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank

“…The possible importance of neonatal endocrine events in regulating the timing of pubertal changes and the achievement of the full reproductive potential of the male primate have not been fully investigated. In several non-primate species, neonatal brain-pituitary-testicular activity has a role in the masculinization of the central nervous system, determination of Sertoli cell number, maturation of feedback systems regulating gonadotrophin secretion, development of the immune system, and social and sexual behavior (Goy & McEwen 1980, Huhtaniemi et al 1986, Baum et al 1990, van den Dungen et al 1990, Mann & Fraser 1996. In primates, neonatal events have been found to influence the timing of puberty and peripubertal and adult gonadotropin and testosterone secretion (Mann et al 1989, Lunn et al 1994.…”

“…It is important to understand the significance of this period for the development of the hypothalamic-pituitary-testes axis, as the frequency of reproductive disorders in boys and men has increased over the past 50 years (Sharpe 1993(Sharpe , 1994. There is also concern that perinatal events such as caesarean section or premature delivery could alter neonatal endocrine events, potentially affecting reproductive maturation and adult sexual function (Mann & Fraser 1996).…”

The triphasic nature of Leydig cell development in humans, and comments on nomenclature

“…Further support for the view that the neonatal phase of Leydig cell development in humans is distinct from the fetal phase comes from the fact that this phase of Leydig cell development and testosterone secretion is dependent upon a reactivation of the hypothalamic-pituitary axis (Mann & Fraser 1996). The elevated neonatal blood testosterone level in humans has been shown to be associated with increased levels of gonadotrophic hormones .…”