Ai-Min Bao, M.D. Ph.D.

Zhejiang University School of Medicine

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

Fetal Development of the Reproductive System

r

附睾

输精管

精囊尿道

MIH ： Müllerian-inhibiting hormone

输卵管

子宫、宫颈、阴道

male female

SRY: Sex-determining Region on the Y Chromosome

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.

Male reproductive system

尿道球腺

Primary sexual organ – Gonad (Testis)

Accessory sexual organ

Epididymis

Ductus deferens

Testis：2 compartments

- Seminiferous tubules

- Interstitium

（曲）细精管

Lumen of Seminiferous Tubule

Sperm

Testis

（睾丸间质细胞）

精原细胞

S初级精母细胞

精细胞

支持细胞、足细胞

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

Sertoli cell: Glycoprotein, Inhibin A (α β1), Inhibin B (α β2)

Function: (-) FSH secretion

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

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.

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;

Infertile: Abnormal physically; Nonmotile or relatively nonmotile

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）

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.

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

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

孕烯醇酮

雄烯二醇

雄烯二酮

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

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）

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

Working mechanism

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

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

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

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

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

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

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

The Male Reproductive System - Quick Review