3120 - Mammalian Physiology

Reproductive Physiology (RP)

Lecture series week 26/27
(March 29th – April 11/13th)
RP.I - Male reproductive system
RP.II and III (RP.II) - Female reproductive system
RP.IV (RP. III) - Pregnancy and placental
development
RP.V (RP. IV) - Fetal development and adaptations to
pregnancy
Lecture Series ZOOM Office
Hours
❖ 5th April (Monday) 2-3 pm

❖ 9th April (Friday) 11- 12 pm

❖ 13th April (Tuesday) 12 - 1 pm

❖ 20th April (7pm) EXAM

 Reproductive
Physiology
Dr. Timothy Regnault
DSB 2021
tim.regnault@uwo.ca

RP Lecture IV series
Fetal development and adaptations
to pregnancy
Fetal (embryo)
RP IV.1- Embryogenesis
development
RP IV.2 - Determination
and of embryonic sex
adaptations to
pregnancy RP IV.3 - Maternal
adaptations
lectures
RP IV.4 - Placental
RP IV.1- RP IV.4 hormones
 Acknowledgement
❖ In this series of video lectures, I will be referring to male and female as the sex
assigned at fertilization and the sex chromosomes present in the cells of this
individual (and therefore the predominant hormones produced). Sometimes this is
also referred to as biological sex. It is important to recognize that someone's gender
may differ from the sex assigned at birth. So, for that reason, I won't be using the
terms male and female in the context of gender identity in this video series.

❖ For some in our community, these reproductive lecture videos deal with sensitive
issues, and while I have done my best to accommodate potential sensitivity issues,
things are changing rapidly in our appreciation of different groups sensitivity to
aspects of reproduction and my apologies if I appear to have failed to make suitable
accommodations. If that is the case we can only learn and understand if those that
have input for change, reach out to me (us – other faculty) to discuss the
opportunities for change, so we can do our best to grow and develop inclusive
educational material appropriate for all members of our community.
 Fetal (Embryo)
development and
adaptations to
pregnancy
lectures Embryogenesis

RP IV.1
 Moving on into week 3 Repro-34/35

and beyond Within the conceptus, gastrulation

❖
converts the bilaminar embryo into
❖ During the third week of development the trilaminar embryo (ectoderm,
conceptus implantation in the uterus wall is mesoderm, endoderm).
complete and trophoblast cells
(syncytiotrophoblast/cytotrophoblast)
continue to invade uterine wall in the process
of early placentation (villi formation).
 Repro-34/35

The bilaminar embryo

Epiblast

Hypoblast
 Repro-34/35

The trilaminar embryo

REPRO
https://commons.wikimedia.org/wiki/Fi
le:HumanEmbryogenesis.svg Embryogenesis - Summary

Hemberger et al., 2020

 Early gonad development –
independent of Y - Somatic Mesoderm will form
the matrix of the gonad.
- This gives rise to the the
primitive genital ridge (B).
- Epithelial cells from here form
the sex chords

- The primordial germ cells, (A)

http://www.embryology.ch/indexen.html

which migrate from outside the

embryo and then colonize the
matrix of the gonad, and will
form the gametes

5. Gonadal (Genital)
ridge (green)
 Early gonad development
- The primordial germ cells (PGC) arise outside the genital ridge
region, in the epithelium of the yolk sac and are first identifiable at
about 3 weeks. These primitive germ cells multiply by mitosis and
then migrate from the yolk sac through the hind gut, and come to lie
within and between the developing sex cords in the primitive gonadal
ridge.

- The genital ridge (aka - primitive gonadal ridge) is a collection of

cells that develop at about 3 to 4 weeks of gestation in the human.
Columns of cells derived from a superficial epithelium overlying the
primitive genital ridge penetrate the tissue to form primary sex cords.
Developmental stages of sex
1) Differentiation of gonad (Sex determination)
2) Differentiation of internal genital organs
3) Differentiation of external genital organs

❖ 1st stage determined by XX or XY programmed gonad

development
❖ The 2nd and 3rd stages dependent on endocrine gonad

❖ Reproductive development has a long maturation time

course, beginning in the embryo and finishing in
puberty.
 To be female or male?
❖ Embryos are gonadally identical, regardless of genetic sex,
until a certain point in development (~6-7 weeks).

❖ Presence of a Y chromosome sets the stage for embryonic

male development.

❖ The Y contains a gene called SRY (sex determining region

of the Y chromosome) or the TDF (testis determining factor).

❖So, sex determination is decided at the point when either an

X or a Y sperm penetrates the ovum.
SRY and sex determination
❖ SRY causes male sex
organs to develop, while
lack of this factor will
cause the embryo to
develop as a female.

❖ In the absence of a Y
chromosome, and
therefore in the absence
of SRY, testes do not
develop and female
X or Y?
differentiation is the
default pathway
http://www.pbs.org/wgbh/nova/miracle/dete_flash.html
Where does SRY act?

+SRY

3 - Gonadal cord
4 - Primordial germ
Goodman Chapter 45

cells (PGC)
7 - Umbilical cord
8 - Intestine
10 - Genital ridge
14 - Aorta
Development of Reproductive
Mullerian Ducts
Tracts SRY
Oviducts
Uterus/Cervix
Upper Vagina
hCG/LH
Wolffian Ducts
Testosterone Efferent Ducts
Sertoli cells Epididymis
AMH/MIF/MIS
Vas Deferens
Seminal Vesicles
The early Leydig cells activity
under the influence of SRY
+ SOX9
Placental
hCG

AMH /MIF

Wolffian duct
SRY

Goodman; Chapter 45
Anti-mullerian hormone
(AMH/MIF/MIS) Under the influence of SPY, Sertoli
cells secrete AMH, up until puberty.
+SRY
AMH/MIF is part of the TGF-ß
family, leading to phosphorylation of
Smad proteins.

In the nucleus, apoptotic genes

are activated, causing apoptosis
of tubular epithelial cells and
absorption of the mullerian ducts.
Week 8 and 16 in the male
Germ cells initially divide
mitotically, ie no meiosis

http://www.pbs.org/wgbh/nova/miracle/dete_flash.html
Week 8, 10 and 16 in female – NO SPY
Germ cells initially divide
mitotically, and very soon
enter meiosis.

http://www.pbs.org/wgbh/nova/miracle/dete_flash.html
Mauvais-Jarvis et al., 2017
Summary
 ensuring satisfactory fetal development
and growth

meeting maternal needs to support the

Adaptations increased physiologic demands of
pregnancy
to
pregnancy providing energy and substrate stores
for the demands of pregnancy, labor,
and lactation

providing the fetus with sufficient

substrates and energy stores to sustain
it through the immediate postnatal
period
Repro-37
Increases in
cardiac
output and
other
changes

Robson et al, 1989

 Maternal

Weight gain and BMR

adaptations
changes and

to pregnancy

Williams Obstetrics, 24th Edition

CHAPTER 4. Maternal Physiology

Williams Obstetrics, 24th Edition

CHAPTER 4. Maternal Physiology
Anabolism transitions to catabolism in
mum to support fetal anabolic processes
Breaking down the weight
gain

Williams Obstetrics, 24th Edition

CHAPTER 4. Maternal Physiology
Human placental and fetal growth -
weight gain and functional and hormonal
capacity
Source of placental estrogen and Repro-33

progesterone and levels in circulation

Dehydroepiandro
sterone sulfate
 Parturition
❖ ~ 40 weeks.

❖ Myometrium ready for contractions together with

a conditioned cervix (softened)

❖ A change in the relationship between estrogens

and progesterone.

❖ The signal for a gradual change likely comes

from the fetus, specifically the adrenal
glands…….cortisol production
Effects of cortisol and corticotropin-releasing
factor (CRH) production in late pregnancy

Progesterone

Prostaglandins

Maturation of
adrenals ~30
weeks of gestation

Goodman Chapter 46 Dehydroepiandro

sterone sulfate
The end of innocence?
❖ Puberty (4 years) begins when the hypothalamus increases pulsatile
release gonadotropin-releasing hormone (GnRH).

❖ Leads to luteinizing hormone (LH) and follicle-stimulating

hormone (FSH) release.

❖ What happens next depends on chromosomal sex

❖ For male sex, LH (Again) and FSH signal production the hormone
testosterone, sperm and other sexual and non-sexual
characteristics.
❖ In female sex, LH and FSH trigger the commencement of the
ovulation cycle and estrogens, and other sexual and non-sexual
characteristics.
The cycle continues….
Thank
you
and
good
luck!