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Controversial Topics in Reproduction: Assisted
Reproduction and the Slippery Slope
Barry R. Zirkin, PhD
Johns Hopkins University
Section A
Male Contraception
Testis
Courtesy of Martin Dym
4
Testis Cross Section
Barry Zirkin
5
Cross Section of a Seminiferous Epithelium
Barry Zirkin
6
The Seminiferous Epithelium
7
Hypothalamic-Pituitary-Testicular Axis
Barry Zirkin
8
Testosterone and Estradiol Implants
Barry Zirkin
9
T-E Implants: Effects on LH
Barry Zirkin
10
Leydig Cells in Untreated Testis
Barry Zirkin
11
Leydig Cells in Contracepted Rat
Barry Zirkin
12
T-E Implants: Effects on Testicular T Secretion
Barry Zirkin
13
Effect of TE Implants on Intratesticular T
Barry Zirkin
14
Effect on Testis of TE Implants
Barry Zirkin
15
Percutaneous Aspiration of Testicular Fluid in Man
Courtesy of Dr. Jonathan Jarrow
16
Human: Serum T and ITT
17
Intratesticular and Serum Testosterone Concentrations
18
Testosterone Plus Levonorgestrel
„
Testosterone plus levonorgestrel suppresses
intratesticular testosterone
− Protocol
X T enanthate, IM, 100 mg weekly
X Levonorgestrel (LNG), 31.25 or 62.5 µg daily
X Treatment period: six months
19
Serum Testosterone
20
Intratesticular Testosterone
21
Sperm Count
22
Section B
How Does Testosterone Function?
Courtesy of Lonnie Russell
Effect on Testis of TE Implants
Barry Zirkin
24
TUNEL Staining after Testosterone/Estradiol Implants
Barry Zirkin
25
Intratesticular Testosterone and Testicular Cell Death
Barry Zirkin
26
How Does Testosterone Function?
Courtesy of Lonnie Russell
27
Effect of Reduced Intratesticular Testosterone
„
Effect of reduced intratesticular testosterone on sertoli
cell cytoarchitecture
Vimentin distribution in sertoli cells
Slides: Barry Zirkin
28
BMF = Bcl2 Modifying Factor
„
„
Actin-associated pro-apoptosis protein
When cells lose attachment to their underlying basal
lamina, BMF interacts with Bcl2 family members to
promote apoptosis
Barry Zirkin
29
Upregulation of BMF
„
Upregulation of BMF in pachytene spermatocytes and
round spermatids in response to TE
Barry Zirkin
30
Hypothetical Model of Germ Cell Apoptosis
Reduced
Intratesticular T
Loss of SertoliSpermatid Adhesion
???
O’Donnell et al. (1996)
Bax, Bcl XL, Bclw
?Effector
BMF
???
Trigger?
Release of Cytochrome c
Caspase 3
Sinha-Hikim et al. (2004)
“executioner”
Kim et al. (2000)
Barry Zirkin
31
Section C
New Ways To Have Kids:
Are We On A Slippery Slope?
New Ways To Have Kids
„
New ways to have kids: are we on a slippery slope?
− Sperm-egg interaction during fertilization
− Assisted reproductive technologies: promise,
controversy, and public health implications
33
Fertilization
34
Maturation of Sperm in the Female Genital Tract
35
In Vitro Fertilization
36
Intracytoplasmic Sperm Injection (ICSI)
37
Sex Selection
38
Cloning
39
How to Clone an Adult Horse
40
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