|Embryology - 26 Sep 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Reading
- 4 Second Trimester
- 5 Third Trimester
- 6 Growth
- 7 Fetal Neural
- 8 Fetal Endocrine
- 9 Fetal Respiratory
- 10 Fetal Genital
- 11 Fetal Renal
- 12 Fetal Gastrointestinal
- 13 Fetal Integumentary
- 14 Fetal Surgical Procedures
- 15 References
- 16 Glossary Links
| This page shows some key events of human development during the fetal period (weeks 9 to 37) following fertilization. The long Fetal period (4x the embryonic period) is a time of extensive growth in size and mass as well as ongoing differentiation of organ systems established in the embryonic period. Clinically this period is generally described as the Second Trimester and Third Trimester. Many of the critical measurements of growth are now carried out by ultrasound and this period ends at birth.
|Changing fetal proportions, not size growth.||Use the links below to get more detailed information about this period of development.|
|Fetal Links: Introduction | Week 10 | Week 12 | Second Trimester | Third Trimester | Fetal Neural | Fetal Blood Sampling | Birth-Weight | Fetal Origins Hypothesis | Fetal Growth Restriction | BGD Practical | Medicine Lecture | Science Lecture | Preterm Birth | Birth | Category:Human Fetus|
- Fetal Graphs: Crown-Rump Length (CRL) | Third trimester CRL | Head Circumference | Head Circumference 2nd Trimester | Liver Weight | Pancreas Weight | Thymus Weight | Small Intestine Length | Large Intestine Length | Length and Weight Changes | Fetal Development
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Jiesi Luo, Lingfeng Qin, Mehmet H Kural, Jonas Schwan, Xia Li, Oscar Bartulos, Xiao-Qiang Cong, Yongming Ren, Liqiong Gui, Guangxin Li, Matthew W Ellis, Peining Li, Darrell N Kotton, Alan Dardik, Jordan S Pober, George Tellides, Marsha Rolle, Stuart Campbell, Robert J Hawley, David H Sachs, Laura E Niklason, Yibing Qyang Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering. Biomaterials: 2017, 147;116-132 PubMed 28942128
Li Ling, Tianqin Wei, Lianli He, Yaping Wang, Yan Wang, Xiushan Feng, Wenqian Zhang, Zhengai Xiong Low-intensity pulsed ultrasound activates ERK1/2 and PI3K-Akt signalling pathways and promotes the proliferation of human amnion-derived mesenchymal stem cells. Cell Prolif.: 2017; PubMed 28940899
Maria Mytilinaiou, Dragana Nikitovic, Aikaterini Berdiaki, Antonis Kostouras, Antonis Papoutsidakis, Aristidis M Tsatsakis, George N Tzanakakis Emerging roles of syndecan 2 in epithelial and mesenchymal cancer progression. IUBMB Life: 2017; PubMed 28940845
Janusz J Jadasz, Lena Tepe, Felix Beyer, Iria Samper Agrelo, Rainer Akkermann, Lucas-Sebastian Spitzhorn, Maria Elena Silva, Richard O C Oreffo, Hans-Peter Hartung, Alessandro Prigione, Francisco J Rivera, James Adjaye, Patrick Küry Human mesenchymal factors induce rat hippocampal- and human neural stem cell dependent oligodendrogenesis. Glia: 2017; PubMed 28940767
Qing Ke, Jia Ye, Siyang Tang, Jin Wang, Benyan Luo, Fang Ji, Xu Zhang, Ye Yu, Xiaoyang Cheng, Yuezhou Li N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita. J. Physiol. (Lond.): 2017; PubMed 28940424
|Fetal Development - Length - Weight|
|Gestational age||Fertilization age||Length||Mass|
|(LMP) (GA weeks)||(weeks)||(cm)||(g)|
|8 (embryonic)||6||1.6 (crown to rump)||1|
|13 (second trimester)||11||7.4||23|
25.6 (crown to heel)
|28 (third trimester)||26||37.6||1005|
L Cussen, J Scurry, G Mitropoulos, C McTigue, J Gross Mean organ weights of an Australian population of fetuses and infants. J Paediatr Child Health: 1990, 26(2);101-3 PubMed 2361065
Katrine Hansen, C James Sung, Carol Huang, Halit Pinar, Don B Singer, Calvin E Oyer Reference values for second trimester fetal and neonatal organ weights and measurements. Pediatr. Dev. Pathol.: 2003, 6(2);160-7 PubMed 12548377
John G Archie, Julianne S Collins, Robert Roger Lebel Quantitative standards for fetal and neonatal autopsy. Am. J. Clin. Pathol.: 2006, 126(2);256-65 PubMed 16891202
Ultrasound CRL Data
|Fertilization and Gestational Age - Crown-Rump Length (measured by ultrasound)|
- Second Trimester
- Week 12 - CRL 85 mm, femur length 15 mm, biparietal diameter 25 mm.
Then look in detail at the head development in a 12 week fetus showing both forms of ossification in the skull.
|Second Trimester Timeline|
|Timeline human development | First Trimester Timeline | Second Trimester Timeline | Third Trimester Timeline|
||Clinical second trimester (GA Clinical Week 14) Second Trimester|| Week 12 - CRL 85 mm, femur length 15 mm, biparietal diameter 25 mm
Hearing Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph
Respiratory Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant
Tongue Week 12 - first differentiated epithelial cells (Type II and III)
Genital female genital canal (80 days) formed with absorption of the median septum
|| Tongue Week 12 to 13 - maximum synapses between cells and afferent nerve fibers
Hearing - Outer Ear Development Week 13 - Meatal plug disc-like, innermost surface in contact with the primordial malleus, contributes to the formation of the tympanic membrane.
|| Tongue Week 14 to 15 - taste pores develop, mucous
Ovary Development 100 days - primary follicles present
Nail Development toenails appear
Head Development facial skeleton remodelling begins
Hearing - Inner Ear Development Week 14 GA 16 - neural-crest-derived melanocytes, now intermediate cells of the stria vascularis, tightly integrate with Na+ /K+ -ATPase-positive marginal cells, which started to express KCNQ1 in their apical membrane.
||Pancreas glucagon detectable in fetal plasma.|
||14 cm|| Hearing Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.
Pituitary adenohypophysis fully differentiated
Respiratory Week 16 to 25 lung histology - canalicular
Hearing - Outer Ear Development Week 16.5 - External auditory meatus is fully patent throughout its length, lumen is still narrow and curved.
Hearing - Inner Ear Development Week 16 GA 18 - cells in the outer sulcus express KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30, but these are not expressed in the spiral ligament. gap junction cartoon
primary follicles begin to form in the ovary and are characterized by an oocyte
glandular urethra forms and skin folds present
|| Neural - Brain development histology week 17
Tooth Development Week 17 - First papilla of the permanent dentition appear (first molar) immediately behind the second milk molar, milk teeth are well advanced (Fetus 180 mm).
|| Tongue Week 18 - substance P detected in dermal papillae, not in taste bud primordia
Skin vernix caseosa covers skin
Spleen Week 18 - alpha-SMA-positive reticulum cells increase in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive white pulp was observed around the arterioles. 
Hearing - Outer Ear Development week 18 - External auditory meatus is already fully expanded to its complete form.
||Neural week 19 neuronal migration ends and the radial glial cells that aided the migration now become transformed into astrocytes and astrocytic precursors.|
|| Pituitary week 20 to 24 growth hormone levels peak, then decline
Skin lanugo, skin hair
Skin 5 months - Hair growth initiated at base of cord, lateral outgrowths form associated sebaceous glands; Other cords elongate and coil to form sweat glands; Cords in mammary region branch as they elongate to form mammary glands.
|| Neural brain cortical sulcation - sylvian fissure, interhemispheric fissure, callosal sulcus, parietooccipital fissure, and hippocampic fissures present
Spleen - Week 22 - antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-smooth muscle actin-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. 
|| Respiratory Week 24 to 40 lung histology - terminal sac
Spleen Week 24 - marginal zone appeared in the alpha-smooth muscle actin-positive reticular framework around the white pulp. Tooth Development Week 24 - Permanent incisors and canines appear. Earliest potential survival expected if born
ovarian follicles can consist of growing oocytes surrounded by several layers of granulosa cells
||Respiratory end month 6 alveolar cells type 2 appear and begin to secrete surfactant|
Third trimester Crown-Rump Length
- Vibration acoustically of maternal abdominal wall induces startle respone in fetus.
- Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs.
- Week 37 to 38 Birth.
|Third Trimester Timeline|
|Timeline human development | First Trimester Timeline | Second Trimester Timeline | Third Trimester Timeline|
|Clinical third trimester (GA Clinical Week 28) Third Trimester||Hearing 3rd Trimester - vibration acoustically of maternal abdominal wall induces startle respone in fetus.|
||Respire Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs|
Tooth Development Week 29 - Permanent premolars (correspond to the milk molars) appear.
Genital male gonad (testes) descending
||Nail Development fingernails reach digit tip|
||Neural brain cortical sulcation - primary sulci present|
||Neural brain cortical sulcation - insular, cingular, and occipital secondary sulci present|
||Nail Development toenails reach digit tip|
||Birth|| Clinical Week 40
Heart pressure difference closes foramen ovale leaving a fossa ovalis
Thyroid TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels
Adrenal - zona glomerulosa, zona fasiculata present
- Links: Third Trimester
Fetal Head Growth
|Second trimester||Second and third trimesters|
|Fetal Fissure Development||Timeline Neural Development|
|Links: Scaled Fissures 13-21 weeks | Fissures 13-21 weeks | Brain Sylvian Fissure | Scaled Brain and Ventricles 13-21 weeks | Scaled Brain, Ventricles and Ganglia 13-21 weeks | Limbic Tract 13-19 weeks | Brain and Ventricles 13-21 weeks | Sylvian Fissure Movie | Neural System Development | Magnetic Resonance Imaging||Timeline human development|
- Links: Neural System Development
- HPA axis established by week 20
- Pituitary functional throughout fetal development
- required for metabolic activity, also in the newborn
- important for neural development
- newborn has total calcium levels (approx 20 grams) accumulated mainly in the 3rd trimester (weeks 28–40)
- fetal parathyroid hormone (PTH) potentially available from 10–12 weeks and PTH does not cross the placenta
- fetus relatively hypercalcemic, active transplacental transport of Ca2+ to fetus
- maternal serum - calcium ions (Ca2+), inorganic phosphate (Pi) and PTH concentrations are within the non-pregnant normal range throughout pregnancy.
- maternal bone turnover increases in the 3rd trimester.
- maternal diabetes can affect fetal pancreas development (increase in fetal islet beta cells).
- testosterone - required during fetal development for external genital development and internal genital tract in male.
- estrogens - secreted inactive precursor converted to active form by placenta.
- Links: Endocrine System Development | Endocrinology - Control of steroid production in the fetal gonads | Neuroscience - The Effect of Sex Hormones on Neural Circuitry
- week 4 - 5 embryonic
- week 5 - 17 pseudoglandular
- week 16 - 25 canalicular
- week 24 - 40 terminal sac
- late fetal - 8 years alveolar
- ovary and testis development
- external genital development
- testis descent
|Tests descent beginning||Tests descent end|
- Links: Genital System Development
- week 32-34 nephron development completed
- term birth nephron number per kidney about 1 million (300,000 to 2 million)
Nephron development has four identifiable developmental stages:
- Vesicle (V) stage (13-19 weeks, second trimester)
- S-shaped body (S) stage ( 20-24 weeks, second trimester)
- Capillary loop (C) stage (25-29 weeks, third trimester)
- Maturation (M) stage (infants aged 1-6 months, neonatal and postnatal)
Fetal developmental features include: the growth and rotation of intestines initially herniated outside the ventral body wall; changes in mesenteries; development of the blood supply and tract wall.
The initial functions of the tract with amionic fluid swallowing and the accumulation of both secretions and swallowed components within the large intestine as meconium.
Fetal Surgical Procedures
There are a range of fatal abnormalities that are potentially amenable to surgical intervention, see recent review link Maternal-Fetal Surgical Procedures.
Some examples include:
- Cardiac Malformations
- Congenital Diaphragmatic Hernia
- Myelomeningocele/Spina Bifida
- Obstructive Uropathy
- Sacrococcygeal Teratoma
- Thoracic Lesions
- Twin-Twin Transfusion Syndrome
- Osman Sulak, Gülnur Ozgüner, Mehmet Ali Malas Size and location of the kidneys during the fetal period. Surg Radiol Anat: 2011, 33(5);381-8 PubMed 21110022
- Hitoshi Ishimoto, Robert B Jaffe Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr. Rev.: 2011, 32(3);317-55 PubMed 21051591
- S C Westerway, A Davison, S Cowell Ultrasonic fetal measurements: new Australian standards for the new millennium. Aust N Z J Obstet Gynaecol: 2000, 40(3);297-302 PubMed 11065037
- Heiko Locher, John C M J de Groot, Liesbeth van Iperen, Margriet A Huisman, Johan H M Frijns, Susana M Chuva de Sousa Lopes Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss. Dev Neurobiol: 2015; PubMed 25663387
- Takashi Satoh, Eiichi Sakurai, Hiroshi Tada, Tomoyuki Masuda Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation. Cell Tissue Res.: 2009, 336(2);287-97 PubMed 19255788
- A Afif, R Bouvier, A Buenerd, J Trouillas, P Mertens Development of the human fetal insular cortex: study of the gyration from 13 to 28 gestational weeks. Brain Struct Funct: 2007, 212(3-4);335-46 PubMed 17962979
- H J Kadhim, J F Gadisseux, P Evrard Topographical and cytological evolution of the glial phase during prenatal development of the human brain: histochemical and electron microscopic study. J. Neuropathol. Exp. Neurol.: 1988, 47(2);166-88 PubMed 3339373
- C Garel, E Chantrel, H Brisse, M Elmaleh, D Luton, J F Oury, G Sebag, M Hassan Fetal cerebral cortex: normal gestational landmarks identified using prenatal MR imaging. AJNR Am J Neuroradiol: 2001, 22(1);184-9 PubMed 11158907
- L B Paquette, H A Jackson, C J Tavaré, D A Miller, A Panigrahy In utero eye development documented by fetal MR imaging. AJNR Am J Neuroradiol: 2009, 30(9);1787-91 PubMed 19541779
- Maternal-Fetal Surgical Procedures. Walsh WF, Chescheir NC, Gillam-Krakauer M, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Apr. (Comparative Effectiveness Technical Briefs, No. 5.) Report | Comparative Effectiveness Research, Health Care
Darren Farley, Donald J Dudley Fetal assessment during pregnancy. Pediatr. Clin. North Am.: 2009, 56(3);489-504, Table of Contents PubMed 19501688
Rosalie M Grivell, Lufee Wong, Vineesh Bhatia Regimens of fetal surveillance for impaired fetal growth. Cochrane Database Syst Rev: 2009, (1);CD007113 PubMed 19160321
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Cite this page: Hill, M.A. 2017 Embryology Fetal Development. Retrieved September 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Fetal_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G