Sperm, when fused to a female female oocyte, provide the male contribution of genomic information, enabling a fully functional progeny to develop. Sperm also contribute a centrosome, sperm borne oocyte activating factors (SOAFs) and possibly mRNA to the oocyte in order to initiate oocyte activation, the utilisation of maternal resources and the generation of a dividing embryo. The main function of sperm is to transport genomic information from a male to the female, travelling a distance of 15cm, which is equivalent to a human swimming 40 miles. On its journey sperm must travel through the torturous environment of the acidic vaginal passage, cervical mucus, uterus and fallopian tube. In order to reach its destination and fertilise an oocyte, sperm have become higly specialised mobile cells.
Spermatogenesis produces haploid male gametes that are able to fertilise a mature oocyte. Due to the limited life span of sperm cells, production is a continous process and maintains a daily output of >200 million differentiated sperm. Sperm production has many steps and from start to finish takes approximately 64 days in humans. Sperm production can be split into 3 stages: spermatogenesis, spermatidogenesis and spermiogenesis.
Spermatogenesis takes place in the seminiferous tubules of the testes, which are relatively quiescent and not fully differentiated prior to puberty. Testes develop from primordial germ cells in the epiblast, which migrate to the hind-gut and colonise the genital ridge. Upon activation by the SRY gene, primordial germ cells cause the development of male characteristic gonads. Fully differentiated testes contain 12-20 seminiferous tubules with both ends flowing into the rete testis.
The unique architecture of the seminiferous tubules provides a self-contained environment supplying all necessary nutrients needed by developing sperm and isolating the lumen from the body's immune system. Spermatogenesis requires an immune privaleged site due to the highly antigenic coats of developing sperm. Antibodies in the blood can hinder sperm function durring maturation, transit through the testis and fertilisation.
Spermatogenesis - production of haploid gemetes
Spermatogenesis begins with spermatogonia, the primordial germ cells of sperm production. Spermatogonia are mitotically inactive until the peri pubertal period where an increase in gonadotrophin hormones from leydig cells of the testes induces massive mitotic proliferation. Spermatogonia then enter meiosis by differentiating into primary spermatocytes. Primary spermatocytes can either self-renew or divide into two secondary spermatocytes completing meiosis one (figure 3).
Spermatidogenesis - production of spermatids
Secondary spermatocytes then divide into four spermatids in order to complete meiosis two (figure 3). Spermatids then have many steps of sperm accessory structure biogenesis to form fully differentiated sperm. This process is called spermiogenesis. Throughout the processes of spermatogenesis, spermatidogenesis and spermiogenesis all spermatogenic cells remain associated with sertoli cells in the seminiferous tubules via cytoplasmic bridges (figure 4). Sertoli cells provide nutrients and signals such as testosterone and FSH required to stimulate and develop each stage of sperm production.
As spermatids develop, they migrate away from the basement membrane of the seminiferous tubules moving towards the lumen. When fully differentiated and mature, sperm cells are released from sertoli cell cytoplasmic bridges and bud off into the lumen of the seminiferous tubules (figure 4). Mature sperm cells are unable to swim so are transported into the epididymus for storage by peristaltic contractions of the seminiferous tubules. The large mass and number of sperm entering the lumen coupled with active fluid secretion by sertoli cells also produces a pressure that pushes the sperm along the seminiferous tubules. In the epididymus, maturation of the sperm continues and the sperm gain the ability to swim prior to ejaculation.
Multiple intrinsic factors are produced in the seminiferous epithelium to regulate and maintain spermiogenesis. These include stem cell renewal factors c-Kit tyrosine kinase receptors and its ligands, and transcription factors such as Oct3/4 and CREB/CREM.
As sperm production is a continuous process involving mass proliferation, quality control is required to prevent the production of imperfect or damaged sperm. Quality control involves:
50% of infertility cases are due to problems in the male partner. Damage to DNA in the male germ line has shown to have serious consequences for the health and development of offspring. Reccurent miscarriages can be caused by damage to genes involved in placental development, many of which are paternally inherited. Sperm DNA damage rates are higher in smokers, older men and individuals who have undergone cancer therapies.
Testicular function is temperature sensitive, which has led to the development of descended testicles in order to keep testicles between 2 and 8 degrees celsius below core body temperature. Heat shock experiments on mice testicles caused damage to chromatin structure, impaired DNA repair mechanisms, reduced fertility, reduced placental weight in successful pregnancies and caused abnormal embryo growth develepment. There is a correlation with male testicular heat stress and infertility that can be experienced in occupations such as bakers, welders, and professional drivers or people with bad posture and tight fitting clothing. High testicular temperatures clearly affect the quality of sperm and consequently fertility. The use of sperm with damaged DNA for intracytoplasmic sperm injection could therefore have long-term health effects for the resultant children.
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