Male repro

• Testosterone


  Important for spermatogenesis, sexual differentiation during embryonic and fetal development, and control of gonadotropin secretion in the pituitary
• Dihydrotestosterone


  Metabolite of testosterone that also begins to act on many tissues during puberty (e.g., male accessory glands and hair follicles)
• Genital ducts and accessory glands

  Produce secretions required for sperm activity and contract to propel spermatozoa and the secretions from the penile urethra
• Semen


  Spermatozoa and the secretions of the accessory glands that are introduced into the female reproductive tract by the penis
• Testes


  • Surrounded by a dense connective tissue capsule, the tunica albuginea, which thickens on the posterior side to form the mediastinum testis
  • Divided into about 250 pyramidal compartments or testicular lobules
• Testicular lobules


  • Contain sparse connective tissue with endocrine interstitial cells (or Leydig cells) secreting testosterone
  • Contain one to four highly convoluted seminiferous tubules in which sperm production occurs
• Testis migration


  1. Develops retroperitoneally in the dorsal wall of the embryonic abdominal cavity

  2. Moved during fetal development to become suspended in the two halves of the scrotal sac, or scrotum, at the ends of the spermatic cords
• Tunica vaginalis


  Serous sac derived from the peritoneum that covers the anterior and lateral sides of the testis
• Sperm formation


  Requires a permissive temperature of about 34°C, maintained in the scrotal sac by various mechanisms
• Mechanisms maintaining testicular temperature

  • Pampiniform venous plexus containing cooler blood from the testis, which draws heat from the arterial blood by a countercurrent heat-exchange system
  • Evaporation of sweat from the scrotum
• Dartos muscle and cremaster muscles


  Move the testes away from or closer to the body, respectively, allowing further control on testicular temperature
• Interstitial tissue of the testis

  • Consists of sparse connective tissue containing fibroblasts, lymphatics, and blood vessels including fenestrated capillaries
  • Contains interstitial cells, or Leydig cells, that develop during puberty as large round or polygonal cells with central nuclei and eosinophilic cytoplasm rich in small lipid droplets
• Leydig cells


  Produce the steroid hormone testosterone, which promotes development of the secondary male sex characteristics
• Testosterone secretion by Leydig cells

  1. Triggered by the pituitary gonadotropin, luteinizing hormone (LH), also called interstitial cell-stimulating hormone (ICSH)

  2. Begins at puberty, when the hypothalamus begins producing gonadotropin-releasing hormone
• Fetal interstitial cells


  Very active during the third and fourth months of pregnancy, then regress and become quiescent cells resembling fibroblasts until puberty when they resume testosterone synthesis in response to the pituitary gonadotropin
• Seminiferous tubules


  • Produce sperm at a rate of about 2 × 10^8 per day in the young adult
  • Each testis has from 250 to 1000 such tubules in its lobules, each measuring 150-250 μm in diameter and 30-70 cm in length
  • The combined length of the tubules of one testis totals about 250 m
  • Each tubule is a loop linked by a very short, narrower segment, the straight tubule, to the rete testis, a labyrinth of epithelium-lined channels embedded in the mediastinum testis
  • About 10-20 efferent ductules connect the rete testis to the head of the epididymis
• Seminiferous tubule epithelium


  • Consists of Sertoli cells, which physically and metabolically support developing sperm cell precursors
  • Consists of dividing cells of the spermatogenic lineage, comprising four or more concentric layers of cells that develop from progenitor cells to fully formed sperm cells over a period of approximately 10 weeks
• Spermatogenesis


  1. Begins at puberty with proliferation of spermatogenic progenitor cells called spermatogonia

  2. Involves mainly mitosis and meiosis, followed by spermiogenesis, the final differentiation process occurring in the haploid male germ cells
• Spermatogonia


  Small round progenitor cells about 12 μm in diameter, occupying a basal niche in the epithelial wall of the tubules, next to the basement membrane, and all closely associated with Sertoli cell surfaces
• Spermatogonia development


  • Stem cells with dark, ovoid nuclei divide infrequently and give rise to cells with more pale-staining, ovoid nuclei that divide more rapidly as transit amplifying (progenitor) cells
  • Type A spermatogonia undergo several unique clonal divisions that leave most of the cells interconnected as a syncytium, becoming type B spermatogonia with more spherical and pale nuclei
  • Each type B spermatogonium then undergoes a final mitotic division to produce two cells that grow in size and become primary spermatocytes, which are spherical cells with euchromatic nuclei
• Meiosis in primary spermatocytes

  1. Replicate their DNA so each chromosome consists of duplicate chromatids

  2. Enter meiosis, during which homologous chromosomes come together in synapsis, DNA recombination occurs, and two rapid cell divisions produce haploid cells
• Primary spermatocytes have 46 (44 + XY) chromosomes, the diploid number, and a DNA content of 4N
• Sertoli cells


  • Support all spermatogenic cells physically and metabolically
  • Phagocytize debris
  • Have endocrine roles affecting spermatogenesis and fetal development of the male reproductive tract
• Immunofluorescence


  • Shows tall Sertoli cells
• Immunoperoxidase & hematoxylin


  • Shows tall Sertoli cells in brown and their close association with numerous spermatogenic cells
• Immunofluorescence


  • Shows distribution and density of Sertoli cells in seminiferous tubules
• Spermatogenesis


  • Spermatogonia divide mitotically to produce more spermatogonia and primary spermatocytes
  • Primary spermatocytes undergo meiosis I to produce secondary spermatocytes
  • Secondary spermatocytes undergo meiosis II to produce haploid spermatids
  • Spermatids differentiate into sperm during spermiogenesis
• Spermiogenesis


  • Flattening of the nucleus
  • Formation of an acrosome resembling a large lysosome
  • Growth of a flagellum (tail) from the basal body
  • Reorganization of the mitochondria in the midpiece region
  • Shedding of unneeded cytoplasm
• Meiosis II is rapid as chromatids in the secondary spermatocyte chromosomes separate into two smaller haploid cells, the spermatids
• Near the lumen but still embedded in Sertoli cells, the spermatids differentiate and undergo the morphological changes required to become motile and capable of fertilization

  
• Each new primary spermatocyte transiently disassembles the tight junctions of the blood-testis barrier and moves from the tubule's basal compartment to the adluminal compartment
• At the same time these cells replicate their DNA, enter meiosis I, and undergo synapsis
• The first meiotic division produces two haploid secondary spermatocytes each with 23 chromosomes
• The spermatogenic progenitor cells, called spermatogonia, are diploid cells containing 46 chromosomes (23 pairs)
• Mitotic divisions of spermatogonia produce new spermatogonia and cells called primary spermatocytes which are committed to meiosis
• Clonal nature of spermatogenesis

  • Stem cells produced by mitotic divisions of spermatogonia remain as separate cells
  • Subsequent divisions of daughter cells have incomplete cytokinesis, leaving the cells attached by intercellular bridges
  • Intercellular bridges allow free cytoplasmic communication and help coordinate progress through meiosis and spermiogenesis
  • Intercellular bridges are lost as haploid spermatids differentiate into sperm
• The cellular events and changes between the final mitoses of spermatogonia and the formation of spermatids take about 2 months
• Spermatogenic cells are not randomly distributed in the spermatogenic epithelium, with cells at different stages of development typically grouped together along the tubule
• Spermiogenesis


  • Includes formation of the acrosome, condensation and elongation of the nucleus, development of the flagellum, and loss of much of the cytoplasm
  • Divided into Golgi phase, cap phase, acrosome phase, and maturation phase
• The acrosome is a specialized type of lysosome containing hydrolytic enzymes that are released during the acrosomal reaction to help the sperm penetrate the egg