Ultrastructural evidence of mature Leydig cells and Leydig cell regression in the neonatal human testis

Abstract

The neonatal period in male development is characterized by an acute rise in serum testosterone, which peaks at 2 to 3 months of age. The purpose of this study is to examine the neonatal human testicular interstitium at 4 months for evidence of Leydig cell maturation, as well as any morphological criteria relating to the fate of Leydig cells during this period, specifically, for signs of cell regression. Leydig cells are described with impressive development of the steroid secreting apparatus, which are consistent with the mature Leydig cells found during early fetal development and in the adult. The outstanding feature of these cells is the "organelle association" of extensive, anastamosing tubules of smooth endoplasmic reticulum (SER), pleomorphic mitochondria with a component of tubular cristae, and abundant microperoxisomes associated with the SER. Well-developed Golgi elements, regionalized RER, and diverse cell inclusions are also characteristics of these cells. Reinke crystals and paracrystalline inclusions are absent. Gap junctions are common in this system and are notable in the asymmetric nature of the adjacent cytoplasmic components. These findings provide a morphologic correlate to the reported neonatal phase of testosterone production in man. Intermediate forms of Leydig cells are described with "organelle associations" including decreased SER with increased lipid droplets, and decreased SER with prominent cytoplasmic filaments and/or dramatic mitochondrial changes supportive of mitochondrial involution. Cells consistent with immature Leydig cells are also present. The rather impressive diversity in cell morphology present during this time frame of 4 months, slightly past the peak in testosterone production, provides evidence of Leydig cell regression and a continuity of the mature neonatal Leydig cells with the immature Leydig cells of childhood (Prince, 1984). There is also some evidence of cell degeneration. Although the developmental history of Leydig cells has been described for years as biphasic, it is time to view Leydig cell development in man as a triphasic event, fetal, neonatal, and pubertal.

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

“…I first suggested that human Leydig cell development is best considered triphasic in 1985 in an abstract in the Anatomical Record, and elaborated on this in a later paper (Prince 1985(Prince , 1990). This conclusion is based on the existing morphological literature.…”

“…Leydig cells are again prominent a few months after birth, with a peak development at 2-3 months (Prince 1985, 1990, Codesal et al 1990). The diverse cell population present at 4 months after birth (slightly past the peak of neonatal development), a mix of mature well-developed Leydig cells and smaller cells which are consistent with regressing cells, supports a continuity, in part, of the neonatal Leydig cell population with the small immature Leydig cells present during childhood (Prince 1984).…”

“…Although some recent reviews and research papers have adopted the concept of triphasic development of human Leydig cells (e.g. Kerr 1992, Saez 1994, (Mietkiewski et al 1966, Pelliniemi & Niemi 1969, Holstein et al 1971, Gondos & Golbus 1976, Codesal et al 1990, Prince 1990. (3) Regression of the neonatal Leydig cell population: a component regresses to immature Leydig cells (ILC), which are present throughout childhood; a broken line leading to a black circle represents the component of the neonatal Leydig cells which degenerates (Prince 1984, 1985, 1990, Codesal et al 1990).…”

“…Kerr 1992, Saez 1994, (Mietkiewski et al 1966, Pelliniemi & Niemi 1969, Holstein et al 1971, Gondos & Golbus 1976, Codesal et al 1990, Prince 1990. (3) Regression of the neonatal Leydig cell population: a component regresses to immature Leydig cells (ILC), which are present throughout childhood; a broken line leading to a black circle represents the component of the neonatal Leydig cells which degenerates (Prince 1984, 1985, 1990, Codesal et al 1990). (4) Maturation of the immature Leydig cells at puberty into a segment of the adult Leydig cell population (ALC): this pubertal developmental phase also involves recruitment of precursor cells (P) (precursor cells include primitive fibroblasts of interstitium and peritubular fibroblasts); F, fibroblastic cells of the adult interstitium (F Prince, unpublished observations, Chemes 1996).…”

Basal Testosterone Secretion and Response to Human Luteinizing, Follicle-Stimulating, and Growth Hormones in Culture of Cells Isolated from Testes of Infants and Children

“…The developmental history of human Leydig cells is a triphasic event: fetal, neonatal, and pubertal (1). Three peaks in serum testosterone levels have been described, viz., during the first half of gestation when the genitalia are formed (2); soon after birth, peaking at 2-3 mo (3); and at puberty (4).…”