Male Reproductive Physiology

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1 Male Reproductive Physiology

2 Overview Anatomy Function Endocrine and spermatogenesis Testis epididymus,vas deferens,seminal vesicles and prostate Hypothalamic pituitary testicular axis Hormones of the male Male Genetics Sperm DNA Spermatogenesis Semen WHO 5 th edition Male sexual function

3 Reference:

4 Anatomy

5 Wall of the Scrotum In the dermis, there is a thin layer of smooth muscle known as the dartos muscle. Contractions of this muscle causes wrinkling of the skin. The cremaster muscle is a thicker layer of skeletal muscle that lowers and raises the testes based on temperature.

6 Inside the Scrotum Each testes is enclosed by the tunica vaginalis, a continuation of the peritoneum that lines the abdominopelvic cavity. A fibrous capsule covers each testis called the tunica albuginea.

7 Testicle The tunica albuginea gives rise to septa (partitions) that divide the testis into lobules (about 250) Each lobule contains 3 or 4 highly coiled seminiferous tubules These converge to become rete testis which transport sperm to the epididymis 7

8

9 9

10 Epididymis Epididymis: Storage and maturation area for sperm Its head joins the efferent ductules and caps the superior aspect of the testis The duct of the epididymis has stereocilia that: Absorb testicular fluid Pass nutrients to the sperm Nonmotile sperm enter, pass through its tubes and become motile (propelled by peristalsis) Upon ejaculation the epididymis contracts, 10 expelling sperm into the ductus deferens

11 Epididymis histology

12 Posterior Bladder 12

13 Accessory Glands: Seminal Vesicles Lie on the posterior wall of the bladder and secrete 60% of the volume of semen Seminal fluid: Fructose: provides energy for the sperm. Fibrinogen: helps turn semen into a bolus that can be readily propelled into the vagina. Prostaglandins: decrease cervical mucus viscosity and stimulate reverse peristalsis of the uterus. Join the ductus deferens to form the ejaculatory duct 13

14 Posterior Bladder 14

15 Accessory Glands: Prostate Gland Plays a role in the activation of sperm Enters the prostatic urethra during ejaculation 15

16 BULBOURETHRAL GLANDS (COWPER S GLANDS) Pea-sized glands inferior to the prostate Produce alkaline mucus prior to ejaculation that neutralizes traces of acidic urine in the urethra 16

17 17

18 18

19 Function Endocrine, Spermatogenesis

20 Spermatogenesis & spermiogenesis Sperm produced in seminiferous tubules Germ cells and Sertoli cells Spermatogenesis diploid spermatogonium to haploid spermatids Spermiogenesis is transformation of spermatids to spermatozoa days

21 Spermatogenesis 21

22 Spermiogenesis: Spermatids to Sperm 22

23 Sperm Sperm have three major regions 1. Head :contains DNA and has a helmet-like acrosome containing hydrolytic enzymes that allow the sperm to penetrate and enter the egg 2. Midpiece: contains mitochondria spiraled around the tail filaments 3. Tail :a typical flagellum produced by a centriole 23

24

25 Testis has 2 distinct components 1. Leydig Cells : Source of Testosterone 2. Seminiferous Tubules :Site of Spermatogenesis

26 Seminiferous Tubules Histology 26

27 Seminiferous Tubules 27

28 Endocrinology

29 LH Stimulates synthesis and secretion of testosterone by Leydig cells. FSH increases LH receptor numbers on cells Testosterone has negative feedback to pituitary, and hypothalamus Testosterone responsible for the maintainence of spermatogenesis

30 FSH Acts with testosterone on seminiferous tubules to stimulate spermatogenesis Major effect is on Sertoli cells

31 Sertoli Cells Rest on Basement membrane connected via tight junctions to form the immunological blood testis barrier Produce androgen binding protein to concentrate locally testosterone to concentration required for spermatogenesis Produce Inhibin as negative feedback to Pituitary Developing sperm are enveloped by the Sertoli cells which influence spermatogenesis

32 Prolactin At normal levels stimulates testosterone secretion At hypersecretion levels associated with decreased production

33

34 Semen WHO 5 th Ed

35 Semen Analysis Masturbation 2 days Sexual Abstinence Sterile plastic jar < 2 hours old Room to body temperature

36 Semen Analysis

37 Semen Analysis Volume > 2ml after 3 days abstinence Liquefaction Coagulum liquefied after minutes

38 Is that enough?

39 Sperm Facts (1) Animal Average Volume of Ejaculate (mls) Range (mls) Human

40 Sperm Facts (1) Species Average Volume of Ejaculate (mls) Range (mls) Rabbit Sheep Human Bull Elephant Stallion Pig

41 Sperm Density or Count

42 Sperm Density or Count Normal > 15 million/ml Oligospermia

43 Sperm concentrations in semen of one man collected weekly over 120 weeks

44 Sperm Facts (2) Species Average # of sperm per ejaculate (in millions) Human 280

45 Sperm Facts (2) Animal Average # of sperm per ejaculate (in millions) Mouse 50 Rat 58 Guinea Pig 80 Rabbit 280 Human 280 Sheep 1000 Bull 3000 Pig 8000

46 Sperm Motility Assessment Motility Grades a. b. c. d. > 25 um/sec (25 um = 5 head lengths or half a tail length) 5 25 um/sec < 5 um/sec (non-progressive motility) immotility Reference Values Normal: 40% or more motile in grades a + b 20% or more with progressive motility (grade a) within 60 minutes of ejaculation

47

48

49 Sperm Morphology Morphology: > 4% Normal Forms

50 Sperm Morphology Assessment

51 Semen Other Cells Leococytes Spermatids

52 Sperm Antibodies Sperm Agglutination Immunobead Test

53 Sperm DNA Integrity DNA integrity important for normal embryo development DNA damage due to Intrinsic factors: protamine deficiency,mutations affecting DNA compaction Extrinsic factors: heat radiation, gonadotoxins DNA Fragmentation refers to damaged sperm DNA that cannot be repaired

54 Sperm DNA Fragmentation tests: 1. Single Cell gel Electrophoresis assay (Comet) or Tunel assay analyze number of breaks in DNA 2. Indirect tests eg Sperm Chromatin Structure Assay SCSA define abnormal chromatin as increased DNA susceptibility No proven treatment regimen so routine testing controversial

55 Influence of Sperm DNA Quality Sperm Chromatin Structure Assay

56 DNA Fragmentation (Halosperm) Big or Medium Halo = OK - Small or No Halo = DNA Damage - >30% is abnormal - <30% is OK

57 Good sperm

58 Bad sperm

59 Male Genetics Males with non obstructive azospermia or severe oligospermia are at increased risk of genetic anomaly compared to fertile men Commonly: Numeric and chromosomal anomalies impair testicular function Y Chromosome microdeletions associated with spermatogenesis defects Cystic fibrosis gene mutations

60 Karyotype Chromosome anomalies 10 to 15% in azospermic men Klinefelter syndrome 47XXY accounts for 2/3

61 Y Chromosome Microdeletions 7%oligospermia,16% azospermia Diagnosis requires specific PCR analysis of sequence tagged sites along the Y chromosome. Most deletions occur in long arm of Y chromosome known as azospermia factor regions:( AZF) Within this region different microdeletions have different effects on sperm production

62

63 Thank you

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