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Ai-Min Bao, M.D. Ph.D.
Zhejiang University School of Medicine
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Human Reproductive System
Reproduction is the biological process by which new individual organisms are produced
Types: Sexual reproduction, Asexual reproduction
Human reproduction belongs to sexual reproduction
接合子
配子
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Fetal Development of the Reproductive System
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r
附睾
输精管
精囊尿道
MIH : Müllerian-inhibiting hormone
输卵管
子宫、宫颈、阴道
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male female
SRY: Sex-determining Region on the Y Chromosome
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Function:
1. Produce estrogen and progesterone;
2. Produce eggs;
3. Receive the sperm;
4. Provide the optimal conditions for the development of the fetus
Function:
1. Produce testosterone;
2. Produce sperm;
3. Deliver sperm to the female vagina.
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Male reproductive system
尿道球腺
Primary sexual organ – Gonad (Testis)
Accessory sexual organ
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Epididymis
Ductus deferens
Testis:2 compartments
- Seminiferous tubules
- Interstitium
(曲)细精管
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Lumen of Seminiferous Tubule
Sperm
Testis
(睾丸间质细胞)
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精原细胞
S初级精母细胞
精细胞
支持细胞、足细胞
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Testis
支持细胞
产生 inhibin (抑制素)、 ABP (雄激素结合蛋白)
Germinal epithelium (睾丸生殖上皮) of the testicle
1: basal lamina;
2: spermatogonia (精原细胞)3: spermatocyte 1st order;
4: spermatocyte 2nd order;
5: spermatid;
6: mature spermatid;
7: Sertoli cell;
8: tight junction (blood testis barrier)
莱氏细胞
产生雄激素
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Sertoli cell: Glycoprotein, Inhibin A (α β1), Inhibin B (α β2)
Function: (-) FSH secretion
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Spermatogenesis: In all the seminiferous tubules during active sexual life, Stimulated by gonadotropic hormones, Begin at an average age of 13 yr, Decreasing markedly in old age, The entire period: 64 days
有丝分裂 第一次减数分裂
第二次减数分裂
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Spermatogenesis is the testicular process in adult males that generates haploid gametes ( 单倍体配子 ) capable of fertilizing ova.
The overall result is that the set of 23 pairs of homologous chromosomes (同源染色体) is reduced to a set of 23 chromosomes per sperm – the corresponding 23 pairs are present in ova.
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Head:Acrosome, containing enzymes
Tail (flagellum): to and fro movement, 1-4 mm/min in a fluid medium
Lifetime: Many weeks in the male genital ducts; 24-48 hrs in the ejaculated semen (精液) ; Several weeks at lowered temperature; Years below - 100°C;
Count: Ejaculated semen during each coitus: 3.5 ml; An average of about 120 million sperm/ml semen (35 ~200 million/ml); < 20 million/ml→ infertile;
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Infertile: Abnormal physically; Nonmotile or relatively nonmotile
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Testis
FSH, LH
Control of Testicular Function
Factors that affect spermatogenesis
Hormonal factors that stimulate spermatogenesis – Testosterone, LH, FSH
Temperature↑ → (-) spermatogenesis
Scrotum (阴囊) As a cooling mechanism - Maintain 2°C difference
Cryptorchidism (隐睾症)
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In response to FSH and testosterone, the Sertoli cells support spermatogenesis. They produce inhibin, estrogen
In response to LH, the Leydig cells produce steroids, including testosterone.
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Androgens
Steroid hormones (Leydig cells)
Types: Testosterone (T, more abundant), Dihydrotestosterone (DHT, more active), Dehydroisoandrosterone (DHIA), Androstenedione (雄烯二酮)
Source:TestesAdrenal glands
Synthesis:from cholesterolP450scc (side chain cleavage)
Secretion Pattern:Pulsatile - Circadian rhythm
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Androgens
At different ages:Stimulated by hCG during fetal development and for 10 or more weeks after birth
Stimulated by LH at the onset of puberty
Transportation: 30 mins~several hrs+ Albumin+ Gonadal steroid-binding globulin (GBG)
Metabolism→ DHT (tissue) or Estrodiol
Degradation into inactive products in the liver
Excretion from the kidney or gut
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孕烯醇酮
雄烯二醇
雄烯二酮
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Functions of testosterone
initiate and maintain spermatogenesis
stimulate the descent of testes - usually into the scrotum during the last 2 to 3 months of gestation. If not, administration of T or gonadotropic hormones
induce differentiation of male accessory reproductive organs and maintain their function
induce male secondary sexual characteristics
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Functions of testosterone
affect the distribution of body hair:↑ growth of hair over the pubis, face and chest↓ growth of hair on the top of the head
affect the voice - causing hypertrophy of the laryngeal
mucosa and enlargement of the larynx→ relatively discordant ‘cracking’ voice → typical adult masculine bass voice
induce the development of acne:↑thickness of the skin,↑secretion by the sebaceous glands (皮脂腺)
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Functions of testosterone
induce muscle development:↑muscle mass - Synthetic androgens used by athletes
Used in old age as a ‘youth hormone’
Effect on bone growth and calcium retention↑ size and strength of bones↑ total quantity of bone matrix Causes calcium retentionused in older men to treat osteoporosisStimulate cessation of bone growthSpecific effect on the pelvis: A funnel-like shape
Effect on metabolism: stimulate protein anabolism
↑ red blood cells
Required for sex drive and may enhance aggressive behavior
RBC Hb
man 124.0~5.5 x 10 /L 120~160g/L
woman 123.0~5.0 x 10 /L 110~150g/L
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Working mechanism
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Capacitation of spermatozoa (精子获能)
occurs in the female genital tract
stimulated by secretions in the vagina, uterus, and uterine tubes
results in capacity to pass through the corona radiata
involves removal of surface coatings and changes in plasma membrane
can be produced in vitro by washing with salt solution
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Acrosome reaction (顶体反应)
stimulated by sperm-binding glycoprotein molecules in thezona pellucida (透明带)
accompanied by Ca2+ influx into sperm
results in the release of acrosomal enzymes (hyaluronidase, 透明质酸酶) and proteolytic enzymes)
involves fusion of the acrosome membrane and plasmaMembrane
necessary for sperm penetration through the zona pellucida
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Fertilization (受精)
Process: The cell membranes of the sperm head and of the oocyte fuse with each other to form a single cell
The genetic material of the sperm and the oocyte combine to form a completely new cell genome, containing equal numbers of chromosomes and genes from mother and father
Two important genetic consequences:1) The diploid chromosome number is restored
(2n) 2) The genetic sex of the zygote is determined (XX
or XY) - the spermatozoa determine the sex of the embryo
There are X - bearing spermatozoa and Y-bearing spermatozoa. The oocyte always contributes an X chromosome
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Why does only one sperm enter the oocyte?
Not entirely known
Ca2+ diffuse inward through the oocyte membrane → multiple cortical granules released from the oocyte →substances from the granules permeate all portions of the zona pellucida →prevent binding of additional sperm
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Regulation of testis function
Hypothlamus-pituitary-testis axis
Hypothlamus: GnRH (also called LHRH), a 10-amino acid peptide, pulsatile release, secreted intermittently a few minutes at a time once every 1 to 3 hrs, ↑ LH (mainly) and FSH sectretion
Pituitary: FSH, LH; glycoproteins, pulsatile release, FSH(+) spermatogenesis, LH↑ T sectretion
Negative feedback control of T secretion:↑T secretion → GnRH secretion↓ → LH secretion↓ →↓ T secretion back to the desired operating level
Testis:T: (-) LH secretion,Inhibin: (-) FSH secretion
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Regulation of testis function
Negative feedback control of seminiferous tubule activity:Inhibin ↑ → FSH secretion ↓ → control of spermatogenesis
Regulation of spermatogenesis by FSH and T Initiate spermatogenesisFSH+ FSH receptor on the Sertoli cells → Sertoli cells grow and secrete various spermatogenic substances
T (DHT) Strong tropic effect on spermatogenesis
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Q: ‘At puberty, the levels of GnRH begin to increase (both in boys and girls), the cause of which remains UNCLEAR…’?
------The most important new development is the ‘Kisspeptin’ idea.
Kiss1 and GPR54 expression increase dramatically during puberty and most probably trigger the events.
Dungan et al., 2006; Endocrinology
Point of view
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The Male Reproductive System - Quick Review