Embryology lecture 1

Primordial germ cells (PGCs)

Cells derived from the epiblast that give rise to gametes; development begins with fertilization

Fertilization

Fusion of haploid gametes, oocyte & sperm, resulting in a diploid embryo

Gametes

Cells whose primary function is to transmit genetic information; derived from primordial germ cells

PGC formation timing

Formed during the 2nd week

PGC migration to yolk sac

PGCs move to the wall of the yolk sac by ~3rd week

PGC migration to genital ridge

In the 4th week, PGCs migrate from the yolk sac towards the genital ridge, along the gut tube & dorsal mesentery

PGC invasion of gonad

PGCs invade the developing gonad by the 6th week

Indifferent gonad

Stage of gonad development before sex differentiation, when it is impossible to distinguish male and female gonads

Primitive sex cords

Formed when PGCs arrive and the genital ridge epithelium proliferates into underlying mesenchyme

SRY gene

Testis-determining factor carried on the Y chromosome; causes primitive sex cords to differentiate into testis cords

Genetically male embryo pathway

XY complex; SRY gene → primitive sex cords differentiate into medullary/testis cords → Testis

Genetically female embryo pathway

XX complex; in absence of SRY, primitive sex cords degenerate & surface epithelium proliferates → cortical cords → Ovary

Meiosis - major functions

1) Meiotic recombination, 2) Reduction of chromosome number to a haploid complement

Meiosis - key events

1 round of pre-meiotic DNA replication, unique Prophase I for genetic exchange, 2 rounds of chromosome segregation (Meiosis I & II)

Mitosis

Cell division giving rise to 2 genetically identical daughter cells, each with 46 chromosomes

Meiosis - chromosome reduction

Reduces chromosome number to a haploid number of 23

Meiotic recombination

Genetic exchange between maternal & paternal alleles, occurring during Prophase I

Leptotene

First stage of Prophase I; condensation of chromosomes

Zygotene

Second stage of Prophase I; pairing/synapsis of homologous chromosomes

Pachytene

Third stage of Prophase I; crossing-over/meiotic recombination occurs

Diplotene

Fourth stage of Prophase I; synapsed chromosomes begin to separate

Male genital ridge germ cell development

Germ cells commit to spermatogenesis; Sertoli cells differentiate, testis cords form; germ cells enter mitotic arrest as spermatogonia until after birth; meiosis I initiated at puberty

Female genital ridge germ cell development

Germ cells commit to oogenesis; synchronously enter meiotic prophase, become oocytes; arrest at diplotene of prophase I at birth; meiosis I completed at puberty

Oogonia

Primordial (earliest) egg cells

Oogenesis

Process by which oogonia differentiate into mature oocytes

3 stages of follicle growth

Primary/preantral → Secondary/antral → Pre-ovulatory

Primary oocyte formation

Oogonia differentiate into primary oocytes, which begin but arrest meiosis I in prophase I until puberty

Primordial follicle

Primary oocyte surrounded by a single layer of flattened follicular epithelial cells

Primary follicle

Formed at puberty when follicular cells proliferate into a stratified epithelium of granulosa cells

Zona pellucida

Layer of glycoproteins surrounding the primary oocyte

Antrum

Fluid-filled space that develops within the secondary follicle

Corona radiata

Layer of granulosa cells surrounding the oocyte once the antrum has enlarged

Completion of meiosis I (oogenesis)

Triggered by luteinizing hormone (LH) stimulation; produces a secondary oocyte (arrested in metaphase II) and a polar body

Ovulation

Release of the secondary oocyte from the ovary; occurs after meiosis I completes

Meiosis II completion (oocyte)

Only completed upon fertilization

Spermatogenesis

Process by which spermatogonia are transformed into spermatozoa; begins at puberty, continues into old age

Spermatogenesis process order

Primary spermatocytes → Meiosis I → secondary spermatocytes → Meiosis II → spermatids

Spermiogenesis

Transformation of haploid spermatids into sperm

Spermiogenesis steps

1) Acrosome formation, 2) Condensation of the nucleus, 3) Loss of cytoplasm, 4) Middle piece & tail formation

Oogenesis vs Spermatogenesis - population

Oogenesis: finite population established at birth; Spermatogenesis: continuously dividing stem cell population

Oogenesis vs Spermatogenesis - gametes produced

Oogenesis: 1 gamete per meiotic event; Spermatogenesis: 4 gametes per meiotic division

Oogenesis vs Spermatogenesis - meiosis timing

Oogenesis: begins fetally, not resumed until puberty; Spermatogenesis: meiosis initiated at puberty

Fertilization location

Occurs in the ampullary region of the fallopian tube

Ovulated (secondary) oocyte features

Surrounded by corona radiata & zona pellucida; completed meiosis I; extruded 1st polar body; arrested at metaphase of meiosis II

Capacitation

Conditioning of the sperm in the female reproductive tract

Contact and recognition (fertilization)

Sperm binds to species-specific receptors (ZP3) on the zona pellucida

Acrosome reaction

Release of proteolytic enzymes from the acrosome to digest the zona pellucida

Sperm fusion with egg membrane

Triggers the cortical granule reaction in the egg, blocking polyspermy (only 1 sperm can enter)

Egg activation

Completion of meiosis (second meiotic division) triggered by sperm fusion

Fusion of genetic material

Formation of the diploid embryo (zygote)

Cortical granule reaction

Cortical granules fuse with the egg membrane and release contents into the perivitelline space, separating the egg membrane from the zona pellucida to block polyspermy

Cleavage

Series of mitotic divisions of the zygote producing blastomeres, still surrounded by the zona pellucida

Blastomeres

Individual cells produced by mitotic cleavage divisions of the zygote

Embryonic genome activation (EGA)

Initiation of gene transcription from the embryonic genome to support subsequent development

Major zygotic genome activation

Burst of RNA transcription between the 2-4 cell stage; essential to sustain further development

Compaction

Around the 8-cell stage; blastomeres maximize contact with each other

Cellular events of compaction

Redistribution of E-cadherin, increased tight junction formation, shape change of blastomeres; defines inner/outer cells which dictates their fate

Trophectoderm

Blastomeres remaining in contact with the outside of the embryo; forms the placenta

Inner cell mass (ICM)

Blastomeres located inside the embryo; forms the embryo proper

Blastocyst cavity (blastocele)

Fluid-filled cavity formed through fluid buildup produced by the trophectoderm

CDX2

Gene/transcription factor whose expression drives trophectoderm lineage segregation

OCT4

Pluripotency factor whose expression drives inner cell mass lineage segregation

ICM unique properties

Source of embryonic stem cells (ESCs); can self-renew and are pluripotent; can give rise to all 3 embryonic germ layers

Hatching

Process by which the blastocyst breaks free of the zona pellucida in order to implant; trophoblast cells secrete proteases to digest the zona pellucida

Blastocyst implantation timing

Occurs around day 6 of gestation

Hypoblast formation

Segregates from the inner cell mass during implantation

Embryonic epiblast formation

The rest of the inner cell mass (not hypoblast) forms the embryonic epiblast

Amniotic cavity

Appears within the epiblast during implantation

Bilaminar embryonic disc

Structure created by the epiblast and hypoblast together after implantation

Epiblast derivatives

Ectoderm of amnion, embryonic ectoderm, primitive streak (notochordal process, embryonic mesoderm, embryonic endoderm)

Hypoblast derivatives

Endoderm of yolk sac, extraembryonic mesoderm

7.5-day human blastocyst

Trophoblast proliferates and loses cell membranes, forming the syncytiotrophoblast, which embeds into the uterine wall

12-day human blastocyst

Blastocyst is entirely embedded into the endometrium of the uterine wall