repro test 3

Day 6-7: Blastocyst implantation

• Apposition: Blastocyst expresses L-selectins and rolls over endometrial surface. Mucin-1 on endometrial surface epithelium repels the blastocyst and prevents it from attaching outside of the window of uterine receptivity

• Adhesion phase: Blastocyst promotes cleavage of mucin 1 -> L-selectins on Trophoblast cells attach to L-selectin receptors on endometrium; Several chemokines and cytokines are essential during this process including Leukemia inhibitory factor (LIF)

• Invasion phase: Trophoblast cells start proliferating and differentiate into inner cytotrophoblast and outer syncytiotrophoblast -> syncyotiotrophoblast invades the luminal epithelium; the embedding of the blastocyst within the stroma (completed 8 days after ovulation)

• Decidualization: Once syncyotiotrophoblast breaches the luminal epithelium, endometrial stromal cells surrounding the implanting embryo differentiate into decidual cells.

  • Progesterone will maintain the decidua

  • Immune cells (macrophages, uterine natural killer cells) promote maternal immune tolerance

  • vascular remodelling and angiogenesis -> change the decidua with the purpose of initiating the development of the placenta

Week 2 after fertilization

Day 14: Inner cell mass becomes a bilaminar embryonic disc /Bilaminar

embryo – 2 layers = epiblast & hypoblast

➢Epiblast forms the amnion; hypoblast forms the yolk sac.

➢Yolk sac and amnion develop simultaneously, days 8 through 14

Extraembryonic membranes

Amnion: epiblast cells form sac filled with amniotic fluid that envelopes embryo : Protection, Cushioning, Temperature regulation, Weightless environment for movement

● Yolk sac: sac hangs from ventral surface of embryo: Forms part of digestive tube, Source of earliest blood cells and blood vessels

● Allantois: out-pocketing at caudal end of yolk sac, Structural base for umbilical cord, Becomes part of urinary bladder

● Chorion: Syncytiotrophoblast plus cytotrophoblast, Encloses embryonic body and all other membranes, Forms projections = chorionic villi -> help form placenta

The period of the embryo ~3rd - 8th week

week 3: Formation of the trilaminar embryo

• Changes in the Chorion -> Formation of chorionic villi

• Gastrulation begins -> Formation of 3 germ layers (ectoderm, mesoderm, endoderm)

• Neurulation -> Formation of the Neural tube

➢week 4: Embryonic folding, heartbeat, formation of limb buds

➢week 4-5: Placentation

➢week 5: Alimentary canal is continuous tube

➢week 7: Feet and hands emerge, rudimentary skeleton, eyes, nose and mouth shape

➢weeks 7-8: Sexual development: Gene expression triggers formation of testes, otherwise ovaries

Chorion villi 2 types

A) Anchoring villi: – penetrate into decidua basalis and anchor chorion vesicle to wall of uterus

B) Absorbing villi: – branch in inter-villus spaces

● Primary villi

● Secondary villi

● Tertiary villi

Diffusion between chorionic blood vessels and maternal blood

• in lacunae -> Oxygen and nutrients diffuse through the walls of the villi and enter the embryo’s blood

• Carbon dioxide and waste products diffuse from the blood in the embryonic capillaries through the wall of the chorionic villi into the maternal blood

Gastrulation

Conversion of bilaminar embryo into trilaminar embryo

• Cells proliferate from both sides of the primitive streak

• Migration of superficial epiblast cells, consisting of totipotent cells to interior creates third layer

• ells push through primitive groove and form mesoderm

Neurulation

• Some cells migrate cranially from the primitive node to form a rod-like structure = notochord

• Notochord incorporated into the pre-cartilaginous vertebrae of the developing embryo -> degenerates, except for nucleus pulposus in the intervertebral discs

• Notochord inductive role in development of the nervous and musculoskeletal systems

  • Neural tube becomes the Central Nervous System (CNS)

  • Neural crest will give rise to the Peripheral Nervous System

Ectoderm (outer layer) (forms from epiblast)

• Nervous system

• Skin, Epidermis

• Hair

mesoderm

• muscle

• bone

• circulatory system

endoderm

• Gastrointestinal tract & associated glands

• Lungs

• Urinary tract

• Mucosae

Embryonic Folding

➢Trilaminar disc folds into three-dimensional embryo

➢Folding of cranial and caudal ends and lateral folding of the embryo occur simultaneously

➢Head fold brings the primitive heart region and the oral membrane onto the ventral surface

➢Lateral folding forms the abdominal walls

The four week old embryo

➢Folding of the embryo

➢Formation of branchial/pharyngeal arches

➢Formation of limb buds

➢Formation of optic pits, optic vesicles, nasal placodes

Placentation at 4 1/2 weeks

➢Placenta = organ that forms from chorion and endometrium to allow embryo/fetus to exchange nutrients and waste

➢Embryo ~6mm

➢Chorionic villi invaded by new blood vessels -> extend to embryo as 2 umbilical arteries and one umbilical vein

➢Chorionic villi provide surface area for exchange

➢Nutrient and gas exchange happens without actual blood exchange

Week 5 development

➢Alimentary canal is a continuous tube from mouth to anus

➢Shortly after, accessory organs bud from mucosa

Human embryo at ~7 weeks after conception

➢Shows development of distinctive features

➢Embryo’s brain and face are growing

➢Nostrils become visible, and the beginnings of the retinas form

Development of the Fetal Circulation

First blood cells arise in yolk sac

➢Unique vascular modifications seen only during prenatal development:

● Umbilical cord connects embryo to the placenta

● 2 Umbilical arteries and 1 umbilical vein

Three vascular shunts:

1. Ductus venosus:

➢Umbilical vein drains into ductus venosus which empties into inferior vena cava, bypasses liver

2. Foramen ovale:

➢Opening in interatrial septum bypasses pulmonary

3. Ductus arteriosus:

➢Pulmonary trunk drains into ductus arteriosus, which drains into aorta, ypasses pulmonary

Lung development

Lungs finish developing last in the fetus

• Baby in womb gets oxygen supply from the placenta

• Surfactant develops late (necessary to keep alveoli inflated)

• Most babies born at 35 weeks will have adequate functioning lungs -> fully developed lungs by 37 weeks

  • Terminal bronchiole 15 - 25 weeks gestation

  • Primitive alveoli from 26 week gestation

  • Mature alveoli after birth

removal of amniotic fluid from lungs

Lungs in fetus while in the womb filled with amniotic fluid

• Active ion-driven alveolar fluid reabsorption is the primary mechanism

• Transient Tachypnea of Newborn: Failure of newborn to clear lung fluid -> respiratory distress from retained lung fluid

Fourth-Sixth Months

➢Sucking, swallowing, breathing

➢Movements – felt by mother

➢Heartbeat can be heard with stethoscope

➢Sweat glands functioning

➢Vernix – protects skin from chapping

➢Lanugo – fine hair helps vernix stick to skin

➢Visual and auditory senses are functional

3 Biological sex determinations

1. Genotypic sex determination: Number and type of sex chromosomes Absence and presence of sex determining genes (SRY, etc.)

2. Phenotypic sex determination: Type of gonads -> ovaries or testicles, Internal reproductive anatomy including ducts or uterus, External genitalia

3. Biochemical sex determination: Sex hormone levels

X and Y chromosomes

• X chromosome large -> ~ 1500 genes, most unrelated to sex

• Y chromosome got smaller -> 83 genes, most related to sex determination and spermatogenesis

SRY on the Y chromosome

• SRY passed on through males -> Y linked inheritance

• SRY codes for testes determining factor (TDF) = transcription factor (direct regulation of Sox9)

• Master regulator of male sex determination -> SRY acts to switch the undifferentiated genital ridge towards testis development

Crossing over in male meiosis

• Crossing over: Tips of X and Y pair in meiosis in pseudo-autosomal regions: PAR1 and PAR2

• Crossover in PAR necessary in male meiosis for proper segregation of chromosomes

• SRY located on boarder of PAR1

• Non-recombining region of Y unique to Y chromosome -> gets passed on without crossing over

Dosage Compensation of X chromosomes

• Additional X chromosome in females would lead to more gene products expressed compared to males

• Compensation mechanism: Inactivation of all X chromosome more than one (lionization) through silencing:

• Packaging into heterochromatin, high levels of DNA methylation, low levels of histone acetylation

• Not all genes silenced i.e. X-inactive specific transcript (Xist)

• Xist RNA = 17kb transcript is not translated -> thought to be a structural component of the inactivation process by physically associating with the inactive chromosome

• one X randomly inactivated ~16 days post fertilization

• Inactive X forms a discrete body within the nucleus = Barr body

Indifferent Gonads

• Initial stages of gonadal development occur during 5th week

• Primordial germ cells migrate to the gonadal ridges = precursor of gonads

• Primitive sex cords for nutritional support to germ cells & regulation of development

Development of the gonads Female

• Without TDF

• MIF absent so Müllerian ducts (paramesonephric ducts) Progenitors of the upper female genital tract

• Ovary develops from the cortex of the indifferent gonad: the medulla regresses

• Default pathway of sexual development in mammals is female

Development of the gonads: Male

• Sexual differentiation begins when sex determining region Y (SRY) on Y chromosome produces testis determining factor (TDF)

• Testosterone present → Wolffian ducts (mesonephric ducts): Progenitors of the upper male genital tract.

• Testis develop from the medulla of the indifferent gonad, the cortex regresses

Development of External Genitalia

• Up till 8th week, sex neutral, undifferentiated external genitalia

• Distinguishing sexual characteristics begin to appear during 9th week

• External genitalia not fully differentiated until the twelfth week

Differentiation of male External Genitalia

• Genitalia start to masculinize at 8-9 weeks of gestation

• Fetal Leydig cells in testes produce testosterone

• Enzyme 5α-reductase-2 required to convert testosterone to the androgen dihydrotestosterone (DHT)

• Complete masculinization of external genitalia by DHT by week 14

• In absence of either testosterone or 5α-reductase-2 -> sex neutral external genitalia develop along female lines

Descent of male testes

• Testes become transferred from the lumbar area into the future scrotum (between 3-9 months)

• Androgens are an absolute requirement for this migration

• Testes reach internal inguinal ring by week 24

• Testis passing through inguinal canal to reach the scrotum

• If improper migration -> undescended testes

Differentiation of female External Genitalia

• Primary female sexual differentiation does not depend on hormones → occurs even if ovaries are absent

• X chromosomes bear genes for ovarian development and an autosomal gene also appears to play a role in ovarian organogenesis

• Ovary is not identifiable histologically until about the 10th week

• Primordial follicles develop at ~ 16 weeks

• Oogonia proliferate > than 7 million primary oocytes produced

Disorders of sex development (DSD)

Incidence of a child with a DSD is 1 : 2000 - 4500 live births

Ambiguous genitalia

• Rare condition where infant’s genital phenotype (external genitals) do not appear to be clearly either male for female

• Many causes have a genetic basis

• Genitals either incompletely developed or characteristics of both sexes present

Ovotesticular syndrome

Incidence in humans 1:100,000

Individuals with both ovarian and testicular tissue

› either one of each gonad

› or gonads are ovotestes with a mixture of both tissues

SRY translocation

• Affects 1:20,000

• SRY located adjacent to PARS region on Y chromosome

• In rare cases, SRY locus translocated onto X chromosome during crossing over

• If sperm with SRY-containing X chromosome fertilises oocyte -> Karyotype will not match phenotypic expression

• Female karyotype (46,XX) plus SRY

• Phenotypically SRY makes male factor and phenotypic expression

• MIF produced -> male internal duct structures present

• Testosterone produced -> external genitalia exhibit full virilization

Swayer syndrome

 Affects 1:80,000

➢ Male karyotype 46, XY

➢ Y chromosome present -> genetically male

➢ lost the SRY region in crossing over, or gene encoding TDF is mutated making it non-functional

● No TDF expressed -> no testicular development

● No testes –> no MIF or testosterone

● Default pathway female -> external female genitalia, a uterus, and fallopian tubes (phenotypically female)

➢ Primitive gonadal tissue underdeveloped -> turns during the first trimester into non-functioning, scar tissue= streak gonads

● No functional ovaries –> do not produce female hormones

● Gonadal dysgenesis (no cells that can develop into ova)

● Primary amenorrhea (absence of a menstrual period by age 15)

Androgen Insensitivity Syndrome

Affects 2-5:100,000 who are genetically male

➢Male karyotype 46, XY

➢Functional SRY gene -> TDF expressed, but can have outwardly female

phenotype due to an underlying androgen insensitivity syndrome (AIS)

➢Testes develop, testosterone is secreted but target cells lack receptors for

the androgens – no masculinizing effects occur

➢SRY has been shown to interact with the androgen receptor

➢Female body type and gender identity but sterile

Testosterone Deficiency

Male karyotype 46, XY

➢Functional SRY region -> TDF expressed, MIF

expressed

➢Can have female phenotype due to Leydig cells in

testes not secreting testosterone

➢Internal structures and gonads will develop into male

structures, but the external genitalia will be female

-> no masculinizing effects occur

➢Individuals are sterile and will not go through puberty

5-α-reductase deficiency

Male karyotype 46, XY

➢Functional SRY region -> TDF expressed, MIF

expressed

➢but 5-α-reductase deficiency -> levels of dihydrotestosterone (DHT) very low

➢Male internal structures and gonads

➢Born with female phenotype or ambiguous genitalia depending on levels of DHT

Mullerian Inhibiting Substance Deficiency

If mutated gene for Mullerian Inhibiting Substance

➢Mullerian female ductal structures will not regress

➢External genitalia will be male due to presence of testosterone

➢Affected individuals usually sterile because testes do not develop normally,

and presence of female ducts interferes with sperm transport

Maternal adaptations to pregnancy

Metabolic Changes:

Human placental lactogen (HPL):

● Stimulates maturation of breasts, fetal growth, and glucose sparing

in mother (reserving glucose for fetus; may cause gestational

diabetes mellitus)

➢Parathyroid hormone and vitamin D levels stay high throughout

pregnancy to ensure adequate calcium for fetal bone mineralization

➢Increased appetite & energy requirements

Placental Hormones order

hPL = human Placental Lactogen

E2 = Estradiol

P = progesterone

PRL = Prolactin

Chorionic villus sampling test (CVS test):

Prenatal diagnosis to determine chromosomal or genetic disorders in the fetus.

➢Biopsy taken of the villi in the placenta during early pregnancy (10-14 weeks)

A) trans-cervical procedure

B) trans-abdominal procedure

➢Tests for sickle cell anemia, hemophilia

➢Risk of miscarriage following CVS is ~1:100

Supplements during pregnancy

• Folate and Folic Acid: Proven to prevent neural tube defects

• Iron: Need for iron increases significantly during pregnancy, Maternal blood volume increases by ~50%

• Anemia during pregnancy has been associated with preterm delivery, maternal depression and infant anemia

• Vitamin D: Fat soluble vitamin important for immune function, bone health and cell division

• 
  

Placenta, umbilical cord and placental blood

Some parents decide to cryopreserve placental tissue, cells or umbilical cord blood or to donate these for embryonic tissues (trophoblast–chorion)

research

➢Placenta and umbilical cord blood: Contains blood rich in hematopoietic stem cells

➢Placental tissue including chorionic villi: Mesenchymal stem cells, Hematopoietic stem cells, Endothelial stem cells (promote e.g. vessel formation), Epithelial stem cells (precursors to grow skin) Abundant source of mesenchymal stromal cells (MSCs)

➢Amniotic membranes: Amniotic membrane contains a combination of growth 

Assessment test of the newborn on Apgar scale (1-10)

● Performed at 1 min & 5 min after birth

● Tests newborn’s health on a scale of 1-10

● 7 or higher indicates that the baby is in good condition

● 4 - 6 means that the baby may need assistance

● Score <4 means that baby may need life saving techniques

Test for congenital heart disease

● Pulse oximetry to measure blood oxygen levels

● Listen to heart and lung sounds

● Detect e.g. septal defects, abnormal heart valves, or irregularities in blood vessels

Blood spot screening test

Screening for rare genetic, hormone-related and metabolic conditions

➢Allows for early identification, early treatment to prevent serious permanent mental and physical disablities

➢~1 in 800 babies have a hereditary genetic health condition

➢Screening tests covered >30 different conditions including

● Phenylketonuria (PKU)

The Pregnant Uterus and hormones

myometrium - Oxytocin receptors

Placenta & placental villi - Progesterone, Estrogen, Prostaglandin

decidua - PGF2

Amnion - PGE2

Chorion - PG Dehydrog

Cervix - IL-8

Hormones during parturition

1. Restricted movement of foetus → stress → cortisol

2. Foetal Cortisol affects placenta: Decreases progesterone & estrogen production, Increases prostaglandin production -> leads to uterine contractions.

3. Vaginal/Cervical stretching stimulates sensory nerve fibers → oxytocin (PP)

4. Oxytocin stimulates prostiglandin production (+ feedback)

Gestational Diabetes Mellitus

3-7% of mothers will develop gestational diabetes

Hyperglycaemia that develops around week 24th - 28th of pregnancy and resolves after birth

Hormones from the placenta can cause cells to become insulin resistant

Preeclampsia

Dangerous complication of pregnancy >20 weeks

➢Affects ~1:10 pregnant women

➢Key features: High blood pressure and protein in the urine -> water retention

➢Can result in deterioration of placenta and insufficient placental blood supply -> can lead to fetus being starved of oxygen

Preterm birth

• Birth of a baby at fewer than 37 weeks' gestational age

• Complications associated with a premature birth:

  • Respiratory distress syndrome (RDS) due to immature lungs (surfactant missing)

  • Difficulty regulating body temperature

  • Poor feeding and slow weight gain

Physiology of the Preterm Infant

Developmental lactase deficiency:

Inadequate lactase activity -> preterm infants unable to digest lactose

➢Lactase activity is a marker of intestinal maturity

➢Interestingly, lactase fortified food in a study did not increase weight gain

➢Alternate metabolic pathways e.g: glucose phosphorylation

Rhesus Disease

Rhesus factor = protein expressed on red blood cells

➢Rhesus disease can occur in Rh- (negative) mothers pregnant with Rh+ (positive) baby

➢If blood mixes e.g. during child birth, incompatible transfusion, trauma, amniocentesis etc. mother can produce antibodies against Rh

➢These antibodies can cross placenta and cause anemia in the foetus

➢Mainly problem in second and subsequent pregnancy -> prophylactic injection of anti-D immunoglobulin (antibodies) so mother does not mount and immune response

breast anatomy

• Duct system: Between 4-18 ducts, Early branching, no lobes, but complex intertwining

• Cooper’s Ligaments

• Alveoli: Hollow sacs of polarized secretory epithelial cells (Lactocytes) drained by a fine duct.

• Myoepithelial cells: Dense, meshwork of smooth muscle encases lactocytes, Contract from oxytocin stimulation, Contraction squeezes milk from alveoli into milk ducts

Lactocytes

• Milk secreting cuboidal and polarized epithelial cells lining the alveoli

• Facing the lumen is a well-developed Golgi apparatus

• Large fat droplets and vesicles containing granules of protein

• Most of the cell is occupied by rough ER and large number of mitochondria

• Surface facing the lumen is covered with microvilli for secretion of milk

Secretory Differentiation

• Breast development during pregnancy = Secretory Differentiation

• Pregnancy Hormones - lead to breast growth

• 'lactogenic hormone complex': oestrogen, progesterone, growth hormone, epidermal growth factor, fibroblast growth factor, insulin-like growth factor, parathyroid hormone related protein, human placental lactogen

• Increasing prolactin and lactose levels during pregnancy linked to breast development

• Initiation of human lactation through secretory differentiation and secretory activation

• Provides milk of appropriate composition and quantity to fully sustain the growth 

Secretory Activation

➢ progesterone withdrawal initiates Secretory Activation

➢ Increase in Lactose associated with milk production

➢ Lactose synthesis determines milk volume (osmotic)

Onset of copious milk secretion

• Day 1- 3 days - colostrum

  • 7 - 123 mL per day

  • Rich in protein: immunoglobulins, lysozyme and lactoferrin

• Day 3 - 6 -> mature milk production

  • 400 - 900mL per day

  • Change in milk composition

  • more lactose & water, less protein

Regulation of lactation

two key hormones:

➢Prolactin: responsible for the development of the mammary glands

and the production of milk.

➢Oxytocin: responsible for the release of milk from the mammary

glands (milk ejection/milk let-down reflex)

Regulation of Prolactin secretion

Milk production regulated through several hormonal mechanisms:

1. suckling -> stimulates nerves - signals via afferent neural pathways through the spinal cord

2. inhibits dopaminergic neurons in the hypothalamus ->inhibition of an inhibitory neurotransmitter = disinhibition -> PRH release from Hypothalamus

3. stimulates the release of prolactin, a peptide hormone produced & secreted by lactotroph cells in the anterior pituitary

4. Thyrotropin releasing hormone (TRH), released from the hypothalamus, also stimulates the release of prolactin (Estrogens increase the sensitivity of lactotrophs to TRH, as well as decreasing their sensitivity to dopamine inhibition)

In non-lactating breast, prolactin (PRL) release is inhibited by PRL-

inhibitory factors including dopamine (dopamine receptors on lactotrophs)

Regulation of Oxytocin secretion

1. Infant suckles the nipple -> stimulation of sensory receptors

2. Positive feedback loop in the breast tissue-> nerve impulses reach the hypothalamus

3. Oxytocin released into blood from posterior pituitary gland to mammary glands

4. oxytocin causes contraction of myoepithelial cells surrounding each alveolus and milk is ejected

5. Entire reflex takes about 30 seconds

Breastmilk

Main components: water, fat, protein, carbohydrates (lactose), minerals &

vitamins -> fat and lactose provide most of the energy

• Digestive Enzymes

• Glutamate/Glutamine (as free amino acids)

• Oligosaccharides

• Influences normal gut flora

• Enzymes promote gut maturation and gut repair

• Enzymes increase bio-availability of trace elements

• Promotes intestinal growth (taurine, ethanolamine, interferon)

Variation in milk composition

Over time:

● Stage of lactation: Very early milk (colostrum) over first few weeks to later months (mature

milk) to provide optimal nutrients and provisions for the growing baby

● During a feed:

› foremilk: start of feeding is thinner and more watery and is usually lower in fat content and

contains more lactose (sugar),

› Hindmilk: later and is higher in protein content and is usually more fatty

● Different compositions throughout a day

› Morning milk can be more watery, while evening milk may be richer, partly due to hormonal

fluctuations

› Number of subsequent feeds

Breastmilk components of the Immune System, Non-specific defence - protective molecules

B12 binding proteins Reduces B12 for bacterial growth

Bifidus Factor Promotes growth of good bacteria

Fatty acids Disrupts virus membranes

Fibronectin Activates macrophages, tissue repair

Gamma-Interferon Activates immune cells

Hormones & Growth Factors Promote maturation of GI tract

Lactoferrin Binds Fe, active peptide

Lysozyme Disrupts bacterial cell walls

Mucins Immobilises bacteria

Oligosaccharides Bind to bacteria prevents attachment

Breastmilk components of the Immune System; Specific Defence:

generated by mother in response to environment

➢Transfer of antibodies to the infant e.g. secretory IgA

Note: Digestive system of infant still immature -> Ab don’t get digested but reabsorbed

in small intestine

➢Immune cells:

● B lymphocytes: Produce specific antibodies

● Macrophages: Kill microbes and produce lysozyme

● Neutrophils: May act as phagocytes

● T lymphocytes: Kill infected cells, mobilize defences

Benefits of Breastfeeding

➢Necrotizing Enterocolitis:

Condition caused by bacterial invasion into the

intestinal wall -> infection and inflammation in the infant’s gut that causes

intestinal tissue to die

➢Breastmilk reduces Necrotizing Enterocolitis in premature babies

83% of Necrotizing Enterocolitis cases occurred in formula fed babies

infant gut microbiome

Mode of delivery strongly influences early infant gut microbiome

➢Infants born by cesarean section have significantly different early gut microbial features compared to vaginally delivered infants

● Infant gut is seeded with microbes from the mother during labor (maternal vaginal and rectal microbiome)

● Differences in colonization stability rather than seeding alone (Bacteroides species present even in CS but disappear after 1 week)

➢Intrapartum antibiotics also influence microbiome

➢Breast feeding and exposure to milk microbiome influences infant gut microbiome

Breastmilk and the microbiome

Complement is a part of the humoral, innate immune system

-> enhances the ability of antibodies and phagocytic cells to clear pathogens and

damaged cells from an organism

➢Maternal complement passed to the offspring through breastmilk

➢-> modulates the composition of the infant’s intestinal microbiota

Lactational Amenorrhea

Breastfeeding induces temporary decline in the women’s fertility

➢Suckling & high milk production inhibits ovulation by increasing prolactin - > high prolactin suppresses kisspeptin neurons -> reduces pulsatile gonadotropin-releasing hormone (GnRH) -> less production of luteinizing hormone (LH) and follicular stimulating hormone (FSH) - > no maturation of follicles, no ovulation, no menstruation