2. MS & EAE
• What is EAE?
– Experimental model for MS in mice
– Induce mice to produce antibodies
against their own myelin (specifically
against myelin basic protein, MBP)
• Conveniently enough, EAE affects
female mice more severely than
male mice! (just like MS in humans)
• Induce EAE by:
– Directly injecting mice with MBP
– Transfer lymph node cells from
injected mouse to the mouse that you
want to have EAE
• Then, measure severity of
symptoms in mouse (clinical score)
3. Origins of sex difference
in EAE?
• Activational effects?
– Remove gonads (GDX)
– Treat GDX’d animals with a hormone:
• Testosterone?
• Estrogen?
• Progesterone?
• Estriol? (one type of estrogen, high levels
secreted during pregnancy)
Progesteron
e & Placebo
4. Origins of sex difference
in EAE?
• Organizational effects?
– Test for this if GDX has no effect on
EAE severity
– Treat animals with T, E2, etc at birth
5. Origins of sex difference
in EAE?
• Sex chromosome effects?
– (remember the four-core genotypes
mice?)
6. Origins of sex difference
in EAE
• Summary:
– Testosterone protects against EAE
– Mice with XX chromosomes are
worse off than mice with XY
– Estriol (one type of estrogen)
protects against EAE
• These are all ideas for treating
humans with MS!
7. DR ARNOLD’S
LECTURE
Main Idea
The hypothalamus, pituitary
gland, and gonads all regulate
each other.
9. The male feedback loop
Hypothalamus
T GnRH
--- +++
Testes Pituitary
FSH &
LH
+++
10. Roles of FSH and LH
FSH LH
Female Stimulates ovaries to produce:
Estradiol during follicular phase
Progesterone during luteal
phase
Both surge at midcycle,
triggering ovulation
Male Stimulates Stimulates
spermatogenes Leydig cells to
is produce T
11. Uterine cycle Steroid hormone Gonadotropin cycle (hormones from
cycle (hormones Ovarian cycle pituitary)
from ovary)
Follicular phase
Luteal phase
12. At beginning of cycle,
estrogen & progesterone
levels are low.
26. After several days, if
fertilization &
implantation do not
occur, the corpus
luteum degenerates
27. Degenerated corpus
luteum stops
producing/secreting
estrogen &
progesterone
28. Now that estrogen &
progesterone levels are at
their lowest again, the cycle
starts all over!
29. What about pregnancy?
• If fertilization & implantation occur
(after ovulation), the corpus luteum
does not degenerate
• Instead, it sticks around and
continues to produce steady levels
of E & P (at least until the placenta
is big enough and mature enough to
take over this job)
• Birth control pills mimic this
“pregnancy-typical” hormone state,
maintaining steady levels of E & P
– At this steady level, estrogen inhibits
LH release
– With no spike in LH, no ovulation
occurs
– With no ovulation, no pregnancies can
occur
31. Only near ovulation
can sex lead to
reproduction
For nearly all mammals, the brief high-fertility window just
preceding ovulation marks the only time when sex can
result in reproduction.
32. Only near ovulation
can sex lead to
reproduction
This simple biological fact has had profound implications
for the evolution of mammalian sexuality.
33. Only near ovulation
can sex lead to
reproduction
Mate choice at high fertility Mating behavior
with
Female Reproductive high-fertility
Success females
Male reproductive
success
Throughout evolution, female reproductive success
(which, in evolutionary biology, just means offspring
number) has depended largely on mating behavior at high
fertility, whereas male reproductive success has depended
largely on mating behavior with high-fertility females.
34. Only near ovulation
can sex lead to
reproduction
Mating behavior
with
Mate choice at high fertility high-fertility
females
Female Reproductive
Success Male reproductive
success
Enhanced sexual Enhanced sexual
interest in certain interest in high-fertility
males at high fertility females
Accordingly, a nearly universal pattern among mammals is
that females exhibit enhanced sexual interest in males
with certain characteristics at high fertility, and males
demonstrate enhanced sexual interest in high-fertility
females.
35. Enhanced sexual Enhanced sexual
interest in certain interest in high-fertility
males at high fertility females
Do these common patterns reveal psychological
adaptations?
36. Psychological adaptations for “fertility-
dependent” mating behavior?
• These common patterns suggest
that...
• Female mammals might possess
psychological adaptations that take
their own fertility into account when
guiding sexual desire & behavior
• Male mammals might possess
psychological adaptations that take a
potential mate’s fertility into account
when guiding sexual desire &
behavior
37. Big question: do humans experience
similar changes in sexuality across
the ovulatory cycle?
(Please note: This is a relatively new area of
research and, at present, we really only have
data on heterosexual women, men, and couples.
As of yet, little is known regarding how these
effects play out among non-heterosexual women
and men and lesbian couples... But stay tuned!)
38. OK, let’s start with women’s mate
preferences...
• Based on evolutionary theory and past
research on nonhuman mammals, we
can predict that women will show
stronger preferences for men with
certain traits at high fertility
• Specifically, we might expect to see
stronger preferences for men with
whatever traits were historically
associated with beneficial genetic
qualities (e.g., genes that promote good
immune function) at high fertility
• Why? Because high fertility (near
ovulation) is the only time when having
sex can result in passing on a partner’s
genes to future offspring... and this has
been true throughout human evolution
39. So, what traits have historically been
associated with beneficial genetic
qualities?
• We don’t know for sure, but we can
make some educated guesses.
• Symmetry is a pretty good guess.
– The basic idea is that we all start out with
a genetic “blueprint” to build a
symmetrical body.
– Ancestral humans probably encountered
all kinds of stressors during development
(e.g., pathogens/parasites).
– Such stressors tend to make it difficult for
the body to develop perfectly
symmetrically (supported by animal and
some human research).
– Ancestral men (or humans in general)
who encountered stressors but still
developed a highly symmetrical body
might have had genes that are protective
against the negative influence of these
stressors.
40. So, what traits have historically been
associated with beneficial genetic
qualities?
• Masculinity is another decent
guess.
– Masculine traits (including a
masculine face, body, voice,
dominant/competitive behavior)
reflect the influence of testosterone.
– Testosterone actually inhibits
(reduces) immune function, possibly
making individuals with higher
testosterone more vulnerable to
pathogens (supported by animal
research).
– Ancestral men who withstood the
negative effects of testosterone and
survived to display pronounced
masculine traits might have had genes
that are protective against pathogens
and other stressors.
41. Putting it all together...
• So, what specific predictions can you
make about changes in women’s
preferences for symmetry and
masculinity across the ovulatory cycle?
• And what is the proposed ultimate
explanation for this pattern?
– I’ll get you started: Ancestral women who
felt more sexually attracted to men with
traits that indicated beneficial underlying
genes (e.g., symmetry and masculinity) at
high fertility, when sex was most likely to
result in conception, may have had a
higher number of surviving kids than
women who showed a different pattern
of preferences across the cycle... What
would be the effect of this over
evolutionary time?
• What is the proposed proximate
explanation for this pattern?
42. What about other preferences?
• Some mate preferences probably
won’t change across the cycle.
• Which ones?
• If, historically, women found a
certain trait desirable in men but
not because it indicated beneficial
genetic qualities (rather, it indicated
some other non-genetic benefit),
then we might expect women to
prefer that trait all of the time,
regardless of their current fertility.
• Can you think of any examples?
43. Summary of predicted effects: Changes
in women’s mate preferences across
the ovulatory cycle
• So, we can predict that...
1. Women’s preferences for traits
that were historically associated
with genetic benefits will
become stronger at high fertility
1. Women’s preferences for traits
that were historically associated
with non-genetic benefits will
not change across the ovulatory
cycle
44. Summary of predicted effects: Changes
in women’s mate preferences across
the ovulatory cycle
• What’s the state of the evidence?
45. Implications for women’s
relationships
• If women’s mate preferences change
across the ovulatory cycle, then women
in relationships might experience
changes in their desire for their partner
across the cycle (women’s preferences
change, but their partner’s qualities stay
the same...)
• What if a woman’s partner lacks the
traits that she finds particularly
attractive at high fertility? What if her
partner has the traits that she finds
particularly attractive at high fertility?
• How might her interest in other men
change as a function of her fertility and
her current partner’s traits?
