Pregnancy Is Hypoxic

When the clever mammals decided to grow the next generation in their placentas (except for the stupid monotremes), they remembered their copepod friends who vertically migrate to the Oxygen Minimum Zone so that they can fatten. If you want the fuel to build up you need to close the damper.

An initiating event in pregnancy is that the trophoblast blocks arterial bloodflow to the uterus, creating an hypoxic enviroment (low oxygen).

Stage of Pregnancy	Uterine Oxygen Level	Key Events
Pre-implantation	~5–8% O₂ (normoxic)	Uterus is moderately oxygenated during the menstrual cycle
Post-implantation (days 6–10)	↓ to ~2–3% O₂ (hypoxic)	Trophoblasts invade; spiral arteries are plugged, reducing maternal blood flow
Weeks 1–10	Hypoxia maintained	HIF-1α stabilized → drives vascularization, placental morphogenesis
After ~10–12 weeks	Gradual rise to ~8–10% O₂	Trophoblast plugs dissolve → maternal blood begins perfusing placenta fully

The cells of the fetus are growing at their fastest rate during the first trimester of pregnancy while hypoxia is maintained. The cells divide and reproduce almost daily. Interestingly this is the same rate that (cancer) cells grow in cell culture. As the baby becomes closer to term oxygen is slowly allowed to return to the fetus. The rate of replication slows.

Trimester	Doubling Time (avg est.)	Relative Growth
1st	~24–36 hours	Fastest (by %)
2nd	~48–72 hours	Moderate
3rd	~72–120+ hours	Slowest (but highest absolute mass gain)

The nature of the cells also changes as oxygen is allowed to return. During the hypoxic times many cells retain their “stemness”: their ability to divide and differentiate into multiple cell types. As the baby nears term only remnant populations of stem cells are left.

Developmental Stage	Gestational Age	% of Stem/Progenitor Cells	Stemness Type	Notes
Zygote	Day 1	100%	Totipotent	Can form both embryo and placenta
Blastocyst (ICM)	Days 5–7	~100% (ICM only)	Pluripotent	Embryonic stem cells in inner cell mass
Gastrulation	Weeks 3–4	~60–70%	Germ layer–committed progenitors	Cells begin losing pluripotency
Organogenesis	Weeks 4–8	~20–30%	Multipotent progenitors	Region-specific stem cells (neural, hematopoietic, etc.)
Fetal growth phase	Weeks 9–20	~5–10%	Tissue-specific stem/progenitor cells	Differentiation dominates, but growth continues
Late gestation	Weeks 21–40	~1–3%	Niche-resident stem cells	Limited to specific tissues (e.g., skin, gut, brain, bone marrow)
At birth	Week 40	~1%	Stem cell niches only	Mostly mature cells; stemness restricted to maintenance compartments

Let’s do some word association.

Hypoxic: Anabolic. Growthy. Stemness. Fetal.

Normoxic: Catabolic. Stable. Adult. Differentiated.