Genetics

Question 1

What are nine causes of male infertility?

Answer 1

1. Endocrine abnormalities
2. Trauma
3. Infection
4. Immunologic infertility
5. Varicocele effect
6. Exposure to toxic chemicals
7. Obstruction secondary to infection
8. Vasectomy
9. Idiopathic

Question 2

What does “idiopathic” infertility mean?

Answer 2

The etiology is currently unknown.

Question 3

What does “etiology” mean?

Answer 3

The study of what causes a certain disease or illness

Question 4

How many, roughly, of all male patients attending a fertility clinic are diagnosed with idiopathic infertility?

Answer 4

Nearly one-quarter, and some researchers would argue one-half

Question 5

Relative to genetics, what is the phenotypical differences between minor and major defects in meiosis, respectively?

Answer 5

Minor defects underlie both evolution and genetic diversity, whereas major defects (when dysfunctional) can lead to tumorigenesis or some genetic syndromes in offspring.

Question 6

What is the difference between euchromatin and heterochromatin?

Answer 6

Euchromatin is more open and less compact, containing genes frequently expressed, while heterochromatin describes regions of the chromosomes less commonly expressed and more densely compacted.

Question 7

Chromosomes can be visualized with certain stains using what type of microscope and during what times of the cell cycle?

Answer 7

Bright light microscopy, just before cell division, respectively

Question 8

How many pairs of chromosomes can be identified in a human?

Answer 8

24 = 22 autosomes + X + Y

Question 9

Explain the origins of the word “chromosome.”

Answer 9

Greek terms meaning chroma (color) and soma (body)

Question 10

When did investigators finally agree that the Y chromosome exists?

Answer 10

In the 1950’s

Question 11

Which gender is heterogametic and why?

Answer 11

Males, X and Y vs. XX

Question 12

What four broad categories can genetics-related male infertility be grouped into?

Answer 12

1. Chromosomal and karyotype abnormalities
2. Partial chromosomal abnormalities
3. Autosomal gene defects
4. Disorders of sexual development leading to male infertility

Question 13

What are two broad categories of disorders related specifically to embryonic sexual development that can lead to male infertility?

Answer 13

1. Congenital Bilateral Absence of the Vas Deferens (CBAVD)

2. Intersex Disorders

Question 14

List six examples of intersex disorders that lead to male infertility.

Answer 14

1. Gonadal development and intersex
2. Hypospadias
3. Cryptorchidism
4. Steroid Biosynthetic Pathways and Metabolism Deficiencies
5. Antimullerian Hormone defects
6. Defects of the Hypothalamic-Pituitary-Gonadal Axis

Question 15

Name two examples of defects of the Hypothalamic-Pituitary-Gonadal axis that result in male infertility.

Answer 15

1. Kallman’s Syndrome (Hypogonadotropic Hypogonadism)

2. Defects in the Gonadotropins and their Receptors

Question 16

When was the first PGD in humans done, by whom, and what was it for, respectively?

Answer 16

Over 20 years ago, Handyside et al., an X-linked recessive disorder, respectively. A female embryo was selected by screening the embryos for the presence of a Y chromosome thus negating the risk of the couple having an affected child.

Question 17

What is one of the most frequent chromosomal anomalies that result in male infertility snd how often does it occur?

Answer 17

Klinefelter Syndrome; 1 in every 500 births (respectively)

Question 18

What is the cause of Klinefelter’s Syndrome?

Answer 18

Duplication of the X chromosome in a male (XXY, XXXY, or XXXXY)

Question 19

What are two signs of patients with Klinefelter syndrome?

Answer 19

1. Usually azoospermic

2. Small atrophic testes

Question 20

Have pregnancies been reported with Klinefelter Syndrome males without ART?

Answer 20

Yes

Question 21

How can sperm be retrieved from patients with Klinefelter Syndrome?

Answer 21

TESE and ICSI

Question 22

Why should infertility patients with Klinefelter Syndrome undergo genetic counseling?

Answer 22

Because even though the offspring born to them with ART have had normal karyotypes to date, it is still possible that the children will be born with an abnormality of the sex chromosome

Question 23

How often does an XX male occur?

Answer 23

1 in 20,000 births

Question 24

What is the genotype, phenotype, and gender identity of an XX male?

Answer 24

Female, Male, Male (respectively

Question 25

Why does azoospermia occur in XX males?

Answer 25

Frequently due to translocated SRY onto X chromosome WITHOUT the AZF region of Y

Question 26

Are XYY males usually fertile?

Answer 26

Yes, but rarely may present with infertility

Question 27

How is the XX male syndrome characterized?

Answer 27

Normal development of the testes and male genital tract with normal masculinzatoin, but small atrophic testes because the presence of two X chromosomes blocks meiosis resulting in azoospermia

Question 28

Should ICSI be attempted for XX males? Why or why not?

Answer 28

No, as they have a Sertoli cell-only phenotype and sperm will not be retrieved.

Question 29

What is Noonan’s syndrome?

Answer 29

Male Turner’s, 46 X,Y - a partial chromosomal defect (deletions of the SRY and AZF region on the Y chromosome, possibly)

Question 30

What are three types of partial chromosomal abnormalities that may lead to male infertility?

Answer 30

1. Translocations or deletions
2. Y chromosome micro deletions
3. CNV’s (both autosomal and on the sex chromosome)

Question 31

What is the “spermatogenesis gene” called?

Answer 31

AZF (Azoospermia Factor Region)

Question 32

Some cytogenecists found, 30 years ago, severely infertile men who had small deletions on what portion of the Y chromosome?

Answer 32

Yq11 (distal portion, long arm)

Question 33

Deletion of which part of the AZF gene has a higher likelihood of finding sperm?

Answer 33

AZFc

Question 34

How are Y micro deletions usually found?

Answer 34

Using multiplex PCR assays

Question 35

How are CNV’s usually identified?

Answer 35

By an assay, array comparative genomic hybridization (aCGH) which is a molecular cytogenetic method to identify CNV’s.

Question 36

What are six Intersex Disorders that can cause male infertility?

Answer 36

1. Gonadal Development genes missing
2. Hypospadias
3. Cryptorchidism
4. Steroid Biosynthetic Pathways and Metabolism Deficiencies
5. AMH
6. Defects of Hypothalamic-Pituitary-Gonadal Axis

Question 37

What is Kallman’s Syndrome?

Answer 37

Hypogonadotropic Hypogonadism - Due to failure of the GnRH-releasing neurons to migrate to the olfactory lobe during development, the gonadotropins are not produced (X-linked disorder).