Several years ago we discovered that spent media from cultured human and bull testes contain components that initiate meiosis in germ cells from fetal mouse testes which have been cultured for 6 days in the spent medium. The active substance(s) was termed meiosis-inducing substance. We later found that human follicular fluid harvested after stimulation with gonadotropins has a similar effect. These meiosis-activating substances have now been identified and characterized in extracts from bull testes and human preovulatory follicular fluid as naturally occurring sterols (meiosis-activating sterols, MAS). MAS are intermediates in the cholesterol biosynthetic pathway and are thus present in all cells which produce cholesterol de novo and from lanosterol. However, MAS accumulate only in the gonads. We discuss the possible physiological role of these sterols in initiating meiosis and in oocyte resumption of meiosis, and their potential use in promoting and preventing fertility.

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Regulation of the onset of meiosis in the developing testis.

Meiotic division begins the process of spermatogenic maturation leading to sperm formation. In contrast to the ovary, in which meiosis is initiated early in development, onset of meiosis in the testis is delayed until the time of puberty. An assay procedure was utilized to evaluate factors responsible for the activation and prevention of meiosis in the developing rabbit testis. Testicular specimens from postnatal rabbits at different ages were used to determine if meiosis-activating substance (MAS) activity and meiosis-preventing substance (MPS) activity could be demonstrated prior to the onset of spermatogenesis. An in vitro system in which undifferentiated gonads from 11.5 day old mouse fetuses are cultured in test and control media was employed. The findings indicate that MAS activity is associated with the onset of spermatogenesis and is also present shortly after birth. Activity of MPS is present throughout much of the prespermatogenic period, with a decline to reach low levels at the onset of spermatogenesis.

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