Week 2 Random Flashcards
1
Q
Timing of migration of Primordial germ cells (PGCs)
A
2nd week: formed in epiblast
3rd week: move to the wall of the yolk sac
4th week: migrate to the developing gonads
5th week: arrive in the gonads then meiosis In the mouse, ~100 PGCs leave the yolk sac →6-7 rounds of mitotic multiplication →4000 enter the primitive gonads
2
Q
Fate of misdirected PGCs
A
Die or Form Teratomas
3
Q
Stages of formation of gametes
A
1) Movement of PGC to gonads
2) Mitosis in gonads (overproduction followed by density mechanism) in oogonia divide only during development, and in males spermatogonia divide during development and puberty
3) Meiosis
4) Structural and Functional maturation of Eggs and Sperm Oogenesis and Spermatogenesis
4
Q
Oogenesis
A
2 million primary oocytes present in the ovaries at birth, only ~40,000-survivie until puberty.
400 (1 per menstrual cycle) are ovulated. Primary oocytes remain in prophase and do not finish their first meiotic division before puberty is reached.
At puberty, one activated primary oocyte produces two haploid cells asymmetric cell division The first polar body The secondary oocyte
The secondary oocyte arrests in metaphase II and is ovulated If penetrated by sperm the second oocyte completes meiosis II, One large ovum (the functional gamete) A tiny second polar body
5
Q
Describe spermatogenesis
A
Spermatogonia (diploid)
Spermatocytes (enter meiosis)
Spermatids (haploid)
->spermiogenesis-> during which they acquire a tail (flagellum) and an acrosome that develops from the Golgi body
Sperm
Spermiogenesis:
- formation of acrosome (penetration enzymes)
- condensation of nucleus
- formation of neck, middle piece, and tail
- shedding of most of the cytoplasm that is phagocytized by Sertoli cells
6
Q
Spermiation
A
Excess cytoplasm and is released into the lumen of the seminiferous tubule
7
Q
How Kareotype is done
A
Leukocyte are isolated, propagated, and toxin are injected Cells are squashed on microscope slide Lightly treated with protease to unwind DNA Stained with Geimsa (non-specific) stain- (total 850 bands; about 50/csome)
8
Q
Position of centromere
A
Metacentric (middle) submetacentric- towards one end acrocentric - at the end
9
Q
p vs q
A
p is short arm q is long arm 7p22.2 46,XY,inv(9).(p11q12)
10
Q
FISH
A
fluorescence in situ hybridization Specific nucleotide probes abeled with fluorescent dyes can be hybridized to the solated chromosomes or nuclei on microscope slides and nalyzed by fluorescence microscopy.
11
Q
Types of probes in FISH
A
Locus specific (label single gene or region) Centromeric probe (labels a specific pair of chromosomes at their centromere) Chromosome painting probe (paint entire chromosome)
12
Q
Two preps for FISH
A
Metaphase nuclei: visualize chromosome structure Interphase nuclei: determine number
13
Q
SKY
A
Spectral Karyotiping FISH with different colors Use in cancer treatment
14
Q
Why chromosomal studies are important
A
Confirmation/determination of diagnosis Prognosis Treatment Monitoring disease – disease progresion and relapse
15
Q
Microarray SNP
A
This analysis is designed to look for imbalances across the genome using SNP (Single Nucleotide Polymorphism) based technology. The SNP microarray testing has probes that can detect imbalances related to hundreds of common Balanced or low level mosaic chromosome changes will not be identified with this technology
16
Q
Use of Cell Free Fetal DNA
A
- Maternal age 35 years or older at delivery - Fetal ultrasonographic findings indicating an increased risk of aneuploidy - History of a prior pregnancy with a trisomy - Positive test result for aneuploidy, including first trimester, sequential, or integrated screen, or a quadruple screen. - Parental balanced robertsonian translocation with increased risk of fetal trisomy 13 or trisomy 21. - 10-15% DNA in mother blood is free fetal DNA - The goal of the test is very specifc trisome 13, 18, 21, XO, XXY
17
Q
false positive false negative
A
Type 1 error, 1-accuracy Type 2 error, 1-sensitivty
18
Q
Balanced / Unbalanced abnormalities of chromosomes
A
Duplications Inversions Inertions Isochromosomes
19
Q
der(14;21)
A
Chromosome derived from 14 and 21
20
Q
Balanced Translocations types
A
Reciprocal translocation Parts of chromosomes are exchanged Can result in mutations at break points or can be unaffected. Problems with segregation at gametogenesis Robertsonian translocation- centric fusion of two chromosomes. No lost coding sequences, carrier unaffected. Problems with segregation at gametogenesis.
21
Q
Balanced vs. Unbalanced chromosomal rearrangements chraracteristic and types
A
Usually lethal 1) Spontaneous new mutation 2) Unbalanced inheritance from balanced rearrangements
22
Q
Reciprocal translocation
A
Balanced chromosomes exchange
23
Q
chromosomal studies can help with
A
Diagnosis (confirmation/determination) Prognosis Recurrence Risk
24
Q
Amniocentesis
A
a prenatal diagnosis of chromosomal abnormalities and fetal infections, and also used for sex determination in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amniotic sac surrounding a developing fetus, and the fetal DNA is examined for genetic abnormalities
25
Cordocentesis
highly specialized prenatal test in which a sample of the baby's blood is removed from the umbilical cord for testing
26
Cytogenetics techniques
1) Karyotyping
2) FISH
3) Microarray SNP Analysis
4) Cell free fetal DNA in Maternal Plasma
27
How does FSH effect ovary?
Production of estrogen
28
What are the functions of Estrogen?
Proliferation of endometrium
Thinning of the cervical mucus
Stimulate pituitary to secrete LH
LH surge at mid-cycle-\> ovulation
Stimulate progesterone production
29
What cells that produce estrogen in female in ovary?
granulosa and thecal cells
30
What are LH surge effects?
completion of meiosis I -\> preovulatory follicle; arrested in metaphase of meiosis II: 3hrs before ovulation
On ovarian surface:
LH↑→Collagenase↑→Digestions of fibers around the follicle
LH↑→Prostaglandin↑→muscular contraction
31
What are cells and their function in Corpus lueteum?
Lutean cells: granulosa cells, thecal cells
Progesterone + Estrogen (turns uterine into secretion phase)
32
How long does it take for an egg to go from ampulla to uterine lumen?
3-4 days
33
Where does the fertilization occur?
At the ampula of uterine tube
34
What secretes hCG?
syncytiotrophoblast
35
When does the corpus luteum stop to produce progesterone?
nProgesterone production until the end of 4th month: trophoblastic secretion of progesterone becomes adequate.
36
Name three phases of fertilization
Phase I: penetration of the corona radiata
Phase II: penetration of zona pellucida
Phase III: Fusion of the oocyte ad sperm cell membranes
37
What is Capacitation?
(wash the sperm by folliciular tubule): Maturation of sperm in female reproductive tractà Removal of the glycoprotein coat and seminal plasma proteins from the sperm plasma membrane (Important for IVF invitro fertiliation and IUI)
38
What is Acrosome reaction?
Release of enzyme by sperm to dissolve zona pellucida (ZP)
39
What events are triggered by entry of sperm to an egg?
Cortical and zona reactions: to prevent polyspermy (forming cortical granules)
Oocyte completes meiosis II
Egg is activated
40
What are Blastomeres?
2-, 4-, 8-cell stages, cells →smaller and smaller
41
What are the results of fertilization?
Restoration of diploid number of chromosomes
Sex determination (at fertilization)
Initiation of cleavage ge:en-US'\>Cell free fetal DNA in Maternal Plasma
42
How does Blastocyst integrate in uterus?
ZP degenerates → uterine fluid penetration → Blastocele (cavity) formation
Inner cell mass → embryoblast
outer cell mass → trophoblast, epithelial wall
43
What are the three epithelial layers in endometrium?
Compact layer, spongy layer, and basal layer
44
Contraceptive methods:
Barrier
Hormone-based
IUD nRU-486 (mifepristone): potent progesterone antagonist nSurgery: Vasectomy & tubal ligation
45
trophoblast differentiation
Week 2 Day 8
Cytotrophoblast (mononucleated) migrate in the Syncitotrophoblast region and lose connection
Syncytiotrophoblast (multinucleated without border)
46
When and how embroyblast differentiate?
Week 2 Day 8
Hypoblast layer (adjacent to blastocyst cavity)
Epiblast layer (adjacent to the amniotic cavity)
47
When and where does the amniotic cavity form?
Week 2 Day 8
Surrounded by epiblast cells
48
When and what makes amniotic memberane?
Week 2 Day 8
Amnioblast (epiblast cells that adjacent to the cytotrophoblasts)
49
What are lacunae? How do they form? Where do they appear? When do they appear?
Week 2 Day 9
Vacuoles fuse in syncytiotrophoblast
50
What types of cells are present in hypoblast and epiblast during Day 9?
Epiblast -- columnar
Hypoblast -- cuboidal
51
What is fibrin coagulum?
A plug that seal the outer layer of endometrium after the embryo implants in uretus.
52
When does the lacuna becomes continous with sinusoids?
Week 2 Day 11-12
53
What is the name of a layer that surrounds Secondary yolk sac?
What is the name of a layer that surrounds amniotic cavity and chorionic cavity?
When do they appear?
Week 2 Day 11-12
Extraembryonic splanchnic mesoderm.
Extraembryonic somatic mesoderm.
54
What is the name of the cavity that is surrounded by extrasomatric membrane?
Chorionic caivty
55
What are the extension of cytotrophoblast called?
When and where do they grow?
Week 2 Day 13
Primary villi
They grow in syncytiotrophoblast
56
When and where does the secondary yolk sac come from?
Week 2
It pinches off from the primitive sac.
Also called definitive yolk sac.
57
What is the exocoelomic cavity?
58
What is the chorion composed of
Week 2
Extraembryonic somatic mesoderm
syncytiotrophoblast
cytotrophoblast
59
What is name that connects embryo to the chorion and what does it become?
Week 2
Connecting Stalk
Umbilical cord
60
Decidua reaction
Week 2 Day 11
Endometrium cells become polyhedral and prepare for implantation.
61
Which chromosomes regulate embryoblast?
Which chromosomes regulate trophoblast?
Female
Male
62
What types of cells are in epiblast?
Pluripotent.
63
What is the first site of hematopoesis?
Primary Yolk Sac
64
beta-hCG uses
Early pregnancy tests
Detecting may have hCG levels low. In normal pregnancy, hCG levels double every 2-3 days.
65
What forms extraembyronic mesoderm?
What does this extraembryonic mesoderm become?
Migration of epiblasts
Splanchnic mesoderm
Somatic mesoderm
66
Utero-placental circulation
Maternal blood lacunae form in the endometrium by invasion of syncytiotrophoblast + Chorionic villi = EARLY PLACENTA
Blood starts flowing in the trophoblast.
67
What are the two components of future planceta?
Endometrium and chorion
68
Oocyte maturation inhibitor
Inhibits progression of oocytes from birth
Small peptide
69
Stages in egg development
PRIMODIAL FOLLICE
cells become cuboidal and produce stratified epithelium of granulosa cells =
PRIMARY FOLLICLE
theca folliculi (stromal cells) separates it from connective tissue
zona pellucida (layer of glycoproteins on the surface of the oocyte, ofrming the zona pellucida)
inner cells become theca interna and outer into theca externa (fibrous capsule)
Antrum develops between granulosa cells
Cumulus oophorus forms around egg
MATURE GRAAFIAN FOLLICLE
70
What is the name of the cell formed by Cleavage?
Blastomere
71
Morula
16 cell ball
Composed of inner and outer cell mass
The inner cell mass give rise to the embryo proper
The outer cell mass give rise to the trophoblast which contributes to placenta
72
Blastula
Uterine fluid enters between cells
Blastocele forms
Cells of the inner cell are called embryoblast and outer cell mas trophoblast
Zona pellucida dissapears
L selectin mediate carbohydrate binding
73
When does the gastrulation begin?
What is gastrulation?
Week 3
Formation of all three germ layers: ectoderm, mesoderm, and endoderm
74
What are three components of primitive streak?
Node, Pit, and Groove
75
Where does the primitive streak go from and to?
From Cloacal membrane (anus) to Buccopharyngeal membrane (mouth).
76
Ovulation steps
Meiosis II is initiated
3 hours before ovulation arrested in methaphase
surface of ovary bulge
stigma (avascular spot) appear
LH increases collagenase activity
Prostaglandin levels also increase
Cumulus oophorus breaks free
Some of the cumulus oophorus cells then rearrange themselves around the zona pellucida to form the corona radiata.
77
Where are epiblast and hypoblast fused?
Buccopharyngeal membrane (mouth) and cloacal membrane (anus)
78
What does the gastrulation form?
Definitive Endoderm
The Intraembryonic Mesoderm
Trilaminar Embryo
79
What happens if primitive streak does not dissapear?
It forms a sacrococcygeal tumor (in newborn)
80
Direction of mesoderm differentiation
Cranial to caudal
81
Layers of mesoderm
Axial Mesoderm
Paraxial Mesoderm (somitomeres and somites)
Intermediate Mesoderm (urogentical system)
Lateral Plate Mesoderm (body wall)
Mesodermal contribution to the chorion (chorion)
82
Prechordal plate
Sets the limit for the cranial migration of notochordal cells
Induces formation of the forebrain
83
What are the results of the notochord formation?
- formation is a series of steps involving fusing with the endoderm
- defines primary axis, gives embryo some rigidity
- induces formation of vertebral column
- induces neuroectoderm to form neural plate
- persists as the nucleus pulposus in the intervertebral disc until early childhood. Likely replaced by connective tissue
84
3rd Week - Week of Threes
- 3 parts to the primitive streak - groove, pit, node
- 3 directions imparted by the primitive streak: dorsal-ventral, right-left, cranial-caudal
- 3 definitive germ layers - ectoderm, mesoderm, endoderm
- 3 types of villi - primary, secondary, tertiary
85
2nd Week - Week of Twos
- 2 trophoblastic layers - cytotrophoblast and syncytiotrophoblast
- 2 layers from the inner mass - epiblast and hypoblast
- 2 yolk sacs - primary and secondary
- 2 extraembryonic mesoderms - splanchnic and somatic
- 2 future cavities - chorionic and amniotic
- 2 components of the placenta - endometrium and chorion
- 2 clinical uses of betahCG
86
What causes neurulation?
What will the neural plate form?
Prechordal plate and notochord induce neural plate formation in the overlying ectoderm.
Neural plate differentiates to neuroectoderm that forms the brain and spinal cord (CNS) during the embryonic period?
87
What is the difference between primary, secondary, and tertiary stem villi?
Primary --cytotrophoblastic core covered by a synctial layer
Secondary -- mesoderm layer, followed by cytotrophoblast, and then synctiotrophoblast
Tertiary villus -- when blood vessels differentiate from mesoderm
88
When tertiary villi form, which side contacts the embryo and which side contacts the baby.
Syncitotrophoblast covers vessels in villia
Cytotrophoblast contacts endometrium
89
Composition of bilaminar embryonic disk.
Epiblast and hypoblast.
90
Prochordral plate
Week 2
Fusion of epiblast and hypoblast that will become mouth.
91
What are some of the different types of genes expressed?
Housekeeping genes
Specialized genes
Finely tuned genes
Normal vs. Diseased gene expression
92
What type of proteins remodel chromatin?
ATP-dependent chromatin remodeling complexes
93
What is The code-reader complex?
It is a scaffold protein bound to multiple proteins that recognize the chromatin modifications.
94
Types of miRNA
Small nuclear RNA (snRNA) - mRNA processing
Small nucleolar RNA (snoRNA) – rRNA processing
Small cytoplasmic RNA (scRNA) – range of function
microRNAs (miRNAs) – post-transcriptional gene-silencing
95
Whare are the functions of TFs
TFIID = TBP + TAFS
TFIIB = recognize BRE element
TFIIF = stabolize interaction TBP/TFIIB
TFIIE = attacts TFIIH
TFIIH = unwinds DNA; phosphorylateion CTD; releases RNA pol from the promtoter
96
What are enzymes involved in mRNA editing?
Phosphatase
Guanyl transferase
Methyl transferase
97
Alternative Splicing mechanisms
Exon skipping
Mutually exclusive exons:
Alternative 5’ donor site:
Alternative acceptor site:
Intron retention:
“Cryptic splice site” - a site whose sequence resembles an authentic splice site and which might be selected instead of the authentic site during aberrant splicing
98
Domainds of TFs
DNA-binding domain (DBD).
Dimerization domain
Activation domain.
99
HOX genes
They control the fundamental architectural plan of the developing embryo.
They are 180 bp long genes, coding for 60 (180 ÷ 3) amino acid long proteins.
They contain the so-called "homeodomain" consisting of a DNA-binding Helix1-Helix2-Helix3 motif (A). Helix3 occupies the major groove of DNA, while the N-terminal arm binds to the minor groove (B).
100
Effects of ubiquitin
Monoubiquitylated = Histone regulation
Multiubiquitylated = Endocytosis
Polyubiquitylated = DNA Repair; Degradation
101
What is the tag that directs proteins to lysosome?
What is the tag of ER resident proteins?
mannose-6-phosphate
KDEL
102
Functions of Amino Acids
a) Proteins
b) Hormones
c) Co-enzymes
d) Nucleotides
e) Alkaloids
f) Cell wall polymers
g) Antibiotics
h) Neurotransmitters
103
Top three molecules by mass in the body
Water
Protein
Fat
104
Modifications in amino acids
–Hydroxylation (proline, lysine)
–Esterification (serine, threonine, tyrosine) •Acetylation •Phosphorylation
–Disulfide bonds (cysteine → cystine)
–Methylation (lysine, histidine, glutamate)
–Carboxylation (glutamate)
105
10 Essential amino acids
These Ten Valuable Amino acids Have Long Preserved Life In Man.
Threonine Tryptophan
Valine Arginine\*
Histidine\* Leucine
Phenylalanine Lysine
Isoleucine Methionine\*
(Tryosine can be made from Phenylalanine)
106
Name the
5 carbon ring
6 carbon ring
Furanose
Pyranose
107
What type of transport occurs at nuclear porest?
Gated transport
108
How do molecules enter nucleus
\<5kDa diffusion
\>60kDa active transport
109
RAN transport
Cargo binds to the carrier (Nuclear Import Receptor).
Carrier enters the nucleus, releases protein, and binds to RAN-GTP
Carrier enters cytoplasm and GTP is hydrolyzed and RAN released.
110
NFAT import
| (IL2 used during Tcell activation)
NFAT is triphosphorylated
High calcium activates calcineurin (protein phosphatase)
NFAT with calcineurin enters nucleus
Gene activation (IL2 transcription)
Low calcium removes calcineurin from NFAT, and NFAT is phosphorylated and exported
111
Three secretory pathways
Signal-mediated diversion to lysosomes
Constitutive secretory pathway (e.g. collagen)
Signal-mediated diversion to secretory vessicles (for regulated secretion) (e.g. digestive enzymes)
112
What is the most abundant protein in mammals
Collagen
16 types but predominant
113
Collagen structure, assembly
Composed of two identical chains (α1) and an additional chain that differs slightly in its chemical composition (α2)
Each chain contains 1050 amino acids
Collagen are translated as longer precurosrs
Co-translational translocation
Default pathway
114
Modifications of collagen in ER and golgi
The signal peptide on the N-terminal is dissolved, and the molecule is now known as **propeptide** (not procollagen).
**Hydroxylation** of lysines and prolines on propeptide by the enzymes prolyl hydroxylase and lysyl hydroxylase (to produce hydroxyproline and hydroxylysine) occurs to aid crosslinking of the alpha peptides. It is this enzymatic step that requires **vitamin C** as a cofactor. In **scurvy**, the lack of hydroxylation of **prolines and lysines** causes a looser triple helix.
**Glycosylation** occurs by adding either glucose or galactose **monomers** onto the hydroxyl groups that were placed onto **lysines,** but not on prolines. From here the hydroxylated and glycosylated propeptide twists towards the left very tightly and then three propeptides will form a triple helix. This molecule, now known as procollagen (not propeptide) is composed of a twisted portion (center) and two loose ends on either end. At this point the **procollagen** is packaged into a transfer vesicle destined for the golgi apparatus.
In Golgi,
polymers of sugars are added
115
Largest capacity organ for protein synthesis
Pancreas
116
What cell in pancreas produce digestive enzymes?
acinar cells
117
Examples of enzymes produced in pancreas
Trypsinogens (1, 2, 3)
Chymotrypsinogen (A, B)
α-Amylase
Procarboxypeptidase A (1, 2)
Lipase
Procarboxypeptidase B (1, 2)
DNase
Prophospholipase (I, II)
RNase
Proelastase
Mesotrypsin
118
How genes for digestive enzymes are regulated?
The contain **pancreas consensus element (PCE)**
A transcription factor, **PTF-1,** present selectively in the exocrine pancreas, binds to this region and is essential for expression of these digestive enzymes.
119
How do digestive enzymes get diverted to secretory vesicles for regulated secretion?
- Creating a transport vesicle involves **assembling a protein coat** on the **cytosolic face** of the budding membrane
- **Different protein coats** select different cargo
- ** GTP-binding** proteins control both **spatial** and **temporal** aspects of membrane exchange
120
Clathrin coats types
trans-Golgi network - transport to lysozomes
trans-Golgi network - storage in secretory vesicles
plasma membrane - receptor-mediated endocytosis
121
Clathrin multimers
Triskelions
122
How digestive enzyme exocytosis is regulated?
By neurohumoral agents
gastrin-releasing peptide (GRP)
cholecystokinin (CCK)
acetylcholine (Ach)
secretin
vasoactive intestinal polypeptide (VIP)
123
What is the name of the response mediates an adaptive response so that the exocrine pancreas can adjust its machinery to the effects of the stressors and proceed with normal synthetic and transport functions
3 functions
unfolded protein response (UPR)
1) chaperones and foldases
2) activate the ERAD
3) global reduction in translation (except for digestive enzymes)
124
quality control system for unusable proteins
ER-associated protein degradation (ERAD)
125
Calnexin function
Ensures that glycosylated proteins are correctly folded.
126
Describe ERAD
Chaperone cannot fold the protein
Protein is feed through channel to cytoplasm
Protein in ubiquitinated
Proteasome degrades protein
127
What is central organ tha regualtes level of cholesterol?
Liver
128
LDL function
Carries cholesterole
apolipoprotein B100 (part of LDL complex) that binds to LDL receptor and signals removal of LDL from ciruclation
129
Cholesterol function
Membrane permeability
Precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D
130
Enzymes in lysozome
Nucleases
Proteases
Glycosidases
Lipases
Phosphatases
Sulfatases
Phospholipases
131
3 pathways to degradation in lysozomes
Autophagy
Phagocytosis
Endocytosis
132
Types of Coenzymes (Cofactors)
Cosubstrate: associates transiently with the active site of an enzyme
Prosthetic group: associates permanently to the active site of an enzyme
133
ATP
energy, energy charge, cation
deltaG = -7kcal/mol
Magnesium
Energy charge = ([ATP] + ½ [ADP])/ ([ATP] + [ADP] + [AMP])
134
Enzymes
AMP + ATP \<-\> ADP + ADP
XMP + ATP \<-\> XDP + ADP
XDP + ATP \<-\> XTP + ADP
Adenylate kinease
Nucleoside monophosphate kinease
Nucleoside diphosphate kinease
X=A,G,U, or C
135
AH2 + NAD+ --\> A + NADH + H+
CH3CH2OH + NAD+ --\> CH3CHO + NADH + H+
Dehydrogenase
Alcohol denhydrogenase
136
Which part of the CoA is reaction?
Sulfhydryl group (-SH)
forms thioester bonds with organic acids
Thioester bond -7kcal/mol
137
What is the function of S-adenosyl methionine
To carry methyl groups
Converted to S-adenosyl homocysteine after the methyl transfer
138
Turner Syndrome characteristics
Only monosomy compatible with life
Absence of ovaries
Webbed neck
Lymphedema of the extremities
Skeletal deformities
Broad chest
Widely spaced nipples
139
Cri-du-chat Syndrome characteristics
Deletion of chromosome #5
cat-like cry
Microcephaly
intelectual disability
congenital heart disease
140
Miller-Dieker syndrome characteristics
a condition characterized by a pattern ofabnormal brain development known as lissencephaly. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves.
141
Angelman's syndrome
Microdeletion on maternal csome15
Intellectual disability
Cannot speak
Exhibit poor motor development
Prone to unprovoked and prolonged period of laughter
142
Prader Willi
Microdeletion on paternal csome15
Hypotonia
Obsety
Intellectual disability
Hypogonadism
Undescended testes
143
Ciclosporin
Calcinurin inhibitor
Reduces immune response
