Reproduction
• Introduction
• sexual determination, differentiation and
development
• Hormones and male reproduction
• Hormones and female reproduction
• Hormones of pregnancy, parturition and
lactation
Parents with diploid somatic cells
Male
Female
Meiotic division
of germ cells
Meiotic division
of germ cells
Haploid ovum
Haploid sperm
Fertilization
Diploid zygote
Mitosis
Offspring with diploid
somatic cells
Fig. 16-1, p.707
Human Chromosome Karyotype
Sexual determination, differentiation and development
• Sex determination
– Genetic sex
• established at the time of conception
• governs the development of gonadal sex
• two most common chromosomal sexdetermining systems:
• Mammalian sex determination means testis
determination—TDF (SRY)
Sex Determination
Chromosomal Sex Determination
•XO/XX systems
(Grasshoppers)
•XX/XY systems
(Some Plants, Insects, Reptiles, all
Mammals)
•ZZ/ZW systems
(Birds, Moths, Some Amphibians and Fish)
Simple molecular pathway for sex determination in the mammalian
gonads
Nature Medicine 14, 1197 - 1213
Evolution of the Y chromosome and SRY
Independent origins of sex chromosomes in birds, snakes, and
mammals.
Vallender E J , Lahn B T PNAS 2006;103:18031-18032
©2006 by National Academy of Sciences
Temperature-Dependent Sex
Determination
Fig. 16-6, p.716
Sexual determination, differentiation and development
• Sexual differentiation
– begins with the establishment of chromosomal sex
at fertilization, followed by the development of
gonadal sex and culminating in the formation of
sexual phenotypes
– Differentiation of Gonads
• differentiation of testis requires TDF
– Differentiation of accessory sex organs and
external genitalia
• mullerian-inhibiting hormone
• testosterone
Sexual determination, differentiation and development
Sexual determination, differentiation and development
Sexual determination, differentiation and development
– Differentiation of the brain
• male vs female
– preoptic area
– gonadotropins secretion pattern
– sexual behavior
• induced by testosterone
– female patterns are predetermined and male
patterns are induced by androgen during critical
period
Sexual determination, differentiation and development
Sexual determination, differentiation and development
• Puberty
– acquisition of reproductive capability and is
manifested by appearance of secondary sexual
characteristics
• hormones of the brain-pituitary-gonadal axis
• appearance of secondary sexual characteristics
• rapid body growth
– Hormonal control of puberty
• Brain is likely the site of activation during puberty
– pulsatile GnRH secretion
– sensitivity to negative feedback of gonadal
steroids
– melatonin may control the timing of puberty
Sexual determination, differentiation and development
Fig. 16-8, p.719
Male reproduction
– Contains seminiferous tubules
– 3 major types of cells: germ cells, Sertoli cells and
Leydig cells
• Leydig cells: produce androgens
• Sertoli cells: support germ cells development
and differentiation
Male reproduction
– Androgen production
•
•
•
•
mainly produced in Leydig cells
cholesterol serves as the substrate
main androgen is testosterone
function of androgens: act in one of 3 forms, DHT, T
and E2
– sex determination and differentiation
– male reproductive organs and secondary sexual
characteristics
– spermatogenesis
– feedback on gonadotropin
Table 16-2, p.720
Male Reproduction
• Spermatogenesis
– differentiation of spermatogonia to spermatozoa
– involves three steps
• proliferation of spermatogonia
• meiosis of spermatocytes to form spermatids
• differentiation of spermatids to form spermatozoa
(spermiogenesis): morphological remodeling
Stages
Chromosomes in each cell
Spermatogonium
2n
(diploid number;
single strands)
Spermatogonia
Mitotic
Proliferation
Primary
Spermatocytes
One daughter cell remains
at the outer edge of the
seminiferous tubule to
maintain the germ cell line
One daughter cell moves
toward the lumen to produce
Spermatozoa
2n
(diploid number;
single strands)
2n
(diploid number;
doubled strands)
First meiotic
division
Meiosis
Secondary
Spermatocytes
n
(haploid number;
single strands)
Second meiotic
division
Spermatids
n
(haploid number;
doubled strands)
Packaging
Spermatozoa
n
(haploid number;
single strands)
Fig. 16-9, p.721
Fig. 16-10, p.722
Hypothalamus
Gonadotropin-releasing hormone
—
+
+
—
Anterior pituitary
LH-secreting
cells
FSH-secreting
cells
FSH
+
Sertoli
cell
LH
+
Testes
Leydig
cell
Spermatogenesis
Inhibin
Testosterone
Fig. 16-11, p.723
Male reproduction
• Regulation of steroidogenesis
– FSH is a major regulator, especially in the
initiation of spermatogenesis
» increases the size of testis
» stimulates the replication of
spermatogonia
» increases LH-R #, contribute to T
production
– Testosterone is essential for maintenance of
spermatogenesis
– Activin: replication of spermatogonia
– Inhibin: inhibits differentiation of
spermatogonia
Male reproduction
• Regulation of androgen production
– LH: major regulator
» Increases cholesterol transport into inner
mitochondrial membrane
» increases enzyme activity (SCC, 3bHSD)
– FSH: enhance LH-R#, protentiates LH effect
– Activin: increases basal T but inhibits LHinduced T production, inhibin blocks activin
effects
Female reproduction
• Anatomy of female reproductive system (human)
Stages
Chromosomes in each cell
Oogonium
2n
(diploid number;
single strands)
Mitotic proliferation
prior to birth
2n
(diploid number;
double strands)
(arrested
in first
meiotic
division)
Primary
oocytes
Enlarged primary oocyte
(first meiotic
division
completed just
prior to
ovulation)
n
diploid number;
doubled strands)
Secondary
oocyte
First polar body
Meiosis
(second meiotic
division
completed after
fertilization)
Second
polar body
Polar bodies
degenerate
Fig. 16-15, p.733
2n
(diploid number;
doubled strands)
Mature
ovum
n (haploid number;
single strands) from
ovum plus
n (haploid number;
single strands) from
sperm for diploid
fertilized ovum with
2n chromosomes
Female reproduction
– Ovary
• produces hormones
• produces eggs
• functional units: ovarian follicles
– fallopain tubes
• transport of eggs
• fertilization occurs here
– uterus
• site for fetal development
Female reproduction
• Ovary contains follicles at different stages of
development
Female reproduction
• Functions of ovary
– folliculogenesis
Female reproduction
• Ovarian
hormonogenesis
– Steroids:
estradiol and
progesterone
Female reproduction
• Estradiol:
– synthesized mainly by granulosa cells
– stimulated by FSH and LH
– act on CNS to maintain libido and sexual behavior
– feedback regulation of GnRH, LH and FSH (+ve or ve)
– function of female reproductive organs
– oocyte maturation
– parturition and lactation
– metabolic functions
» anabolic: weight gain
» bone mineral deposition
Female reproduction
• Progesterone
– synthesized mainly by corpus luteum
– stimulated by LH (primed by FSH)
– act on CNS to increase sexual receptivity
– feedback regulation of GnRH, LH and FSH (-ve)
– effects on reproductive tract
– pregnancy
– metabolic functions
» increases basal metabolic rate and thus
thermogenic action
Female reproduction
• Others
– ovary also produces many nonsteroidal hormones
– inhibin and activin
» regulate FSH secretion and ovarian function
– prostaglandins
» PGF2a induces CL regression
» PGF2a and PGE2 required for ovulation
– insulin-like growth factor
» stimulates granulosa cell proliferation; inhibits
apoptosis; induces steroidogenesis; induces
maturation
Female reproduction
– Reproductive cycle
• cyclic change of reproductive activity
• seasonal reproductive cycle
– related to environmental changes, e.g.
photoperiod, temperature, food availability,
etc.
• estrous cycle (menstrual cycle in primates)
– visible sign of ovulation
– a behavior strategy to ensure that the
female is mated at the time of ovulation
Female reproduction
– human menstrual cycle
• cycle of ovarian activity that repeat at
approximately one-month interval
(menstru=monthly)
• menstruation is used to indicate the periodic
shedding of endometrium, which become
thickened prior to menstruation under
stimulation by ovarian steroids
• shedding of endometrium is accompanied by
bleeding
Female reproductive physiology
Female reproductive physiology
Ovarian events during menstrual cycle
Female reproduction
• Regulation of ovarian functions
– Follicular phase:
» FSH level is elevated at the beginning of the
cycles
» FSH stimulates follicular development and
production of E2 and inhibin
» E2 and inhibin feedback to inhibit FSH and
thus FSH level decreases
» the follicle that has the highest sensitivity to
FSH will be selected and develops into a
mature follicle
» growth of mature follicle is accompanied by
rapid increase in E2
» E2 triggers LH surge (positive feedback)
Female reproduction
– ovulation: rupture of follicular wall and release of oocyte
» triggered by LH surge
» other hormones: prostaglandin: histamine
– Luteal phase
» CL formed
» progesterone produced by CL
» together with E2 feedback to suppress FSH and LH :
prevent new follicular development
» if pregnancy occurs, hCG stimulates progesterone
production and CL function maintained
» if no implantation, CL regresses and progesterone
level declines (about day 22)
Female reproductive physiology

Regulation of uterine events during menstrual
cycle
• menstrual phase
– starts at the first day of bleeding (last 3-5
days)
– endometrium degenerates
– resulted from decrease in progesterone
• proliferative phase
– between the cessation of menstruation and
ovulation (about 10 days)
– endometrium regenerates and thickens
– estradiol induces endometrium and
myometrium growth, as well as
progesterone receptors
Female reproduction
• secretory phase
– between ovulation and the onset of next
menstruation
– occurs when the ovary is at luteal phase
– under the action of progesterone and estradiol,
endometrium is prepared to accept and nourish an
embryo
» thick, vascular and “spongy” in appearance
» accumulation of glycogen and various enzymes
– Progesterone also inhibits myometrium activity
Female reproduction

Menopause
 cessation of ovarian activity
 during postmenopause years, ovaries are
depleted of follicles and stop secreting estradiol
 due to failure in the ovary, not pituitary
 a weak estrogen (estrone) is produced by
adipose tissue from an androgen produced by
the adrenal gland
 withdrawal of estradiol is responsible for most
symptoms of menopause
Fig. 16-17, p.736
Hypothalamus
GnRH
—
+
+
—
Anterior pituitary
LH-secreting
cells
FSH-secreting
cells
FSH
LH
+
+
Ovary
Mature follicle
Inhibin
Ovulation
High levels
of estrogen
Fig. 16-18a, p.737
Hypothalamus
GnRH
—
+
+
Anterior pituitary
—
LH
+
Ovary
Corpus luteum
Inhibin
High levels
of estrogen
Fig. 16-18b, p.737
—
Hypothalamus
Gonadotropin-releasing hormone
(GnRH)
+
—
—
+
Anterior pituitary
LH-secreting
cells
FSH-secreting
cells
FSH
LH
+
+
Ovary
Follicular
development
+
Low levels
of estrogen
Inhibin
Fig. 16-18c, p.737
Fig.1 6-21, p.744
Blastocoele
Blastocyst
(cross section)
Becomes amniotic sac
Morula
Cleavage
Spermatozoa
Inner cell mass
Ovum
(cross section)
Destined to
become fetus
Trophoblast
Accomplishes
implantation
and develops
into fetal
portions of
placenta
Fertilization
Secondary
oocyte
(ovum)
Implantation
Ovulation
Ovary
Endometrium
of uterus
Fig. 16-22, p.746
Pregnancy, parturition
and lactation
•Implantation
•fixation of embryo in the
wall of uterus
• begins with attachment of
blastocyte to endometrium
and end with the formation
of placenta
Umbilical cord
Amniotic sac
Pool of maternal blood
Placental villus
Intervillus space
Uterine decidual tissue
Maternal arteriole
Maternal venule
Fetal vessels
Chorionic tissue
Chorion
Placenta
Umbilical
vein
Umbilical
artery
Fig. 16-24, p.748
Pregnancy, parturition and lactation
– Maternal recognition of
early pregnancy
• human chorionic
gonadotropin rescues
corpus luteum
Pregnancy, parturition and lactation
– Placenta
• Transfer nutrients, gases, and waste products
between the mother and fetus
• barrier between mother and fetus
• produces hormones
– regulate fetal growth and development
– regulate maternal physiology
– support pregnancy
– parturition
Pregnancy, parturition and lactation
– Placental hormones
• steroids
Fig. 16-26, p.751
Pregnancy, parturition and lactation
• Progesterone
– produced by placenta from cholesterol
– maintenance of uterine structure and function
– mammary growth and development
– feedback on gonadotropin
– substrate for cortisol production in fetal adrenal
gland
• Estrogens
– produced by the placenta from precursors
derived from adrenal gland
– important for parturition and lactation
Pregnancy, parturition and lactation
– Peptide hormones
• hCG
– acts at same receptor as LH
– stimulates progesterone production
– regulate development of fetal adrenal and
gonad
• hPL
– maternal intermediary metabolism
– fetal growth
– mammary gland differentiation
– steroidogenesis
Pregnancy, parturition and lactation
• Parturition
Pregnancy, parturition and lactation
• Parturition
– delivery of baby at term
– requires two physiological changes
– cervical softening to reduce the resistance to
expulsion of baby
– coordinated myometrial contraction to increase
intrauterine pressure
– induced by hormones
Pregnancy, parturition and lactation
• Lactation
– secretion of milk by mammary glands
– mammals are characterized by lactation
– lactation provides a primary source of nutrition for
new-born
– this process includes
• milk production
• milk let-down
Pregnancy, parturition and lactation
• Regulation of mammary gland development
– stimulated by estrogen, progesterone, PRL,
GH and cortisol
• Regulation of milk production
– PRL: essential for milk production
– Cortisol: synergizes with PRL to initiate
lactation
– Estradiol: increases PRL and cortisol
– progesterone: inhibitory
– prostaglandins: increase PRL and cortisol
– insulin: lipogenesis
Pregnancy, parturition and lactation
• Milk ejection
– accomplished by contraction of the
myoepithelial cells surrounding the alveoli
– contraction is under the control of oxytocin
– oxytocin is released in response to suckling
– suckling also induces prolactin release
which stimulates more milk production
Pregnancy, parturition and lactation