Int J Anat Res 2017, 5(1):3496-500. ISSN 2321-4287 3496

Original Research Article

MICRO-MORPHOMETRIC STUDY OF SKIN IN DEVELOPING HUMANFETUSES AND ITS CLINICAL RELEVANCEFazal ur Rehman *1, Nazim Nasir 2.

ABSTRACT

Address for Correspondence: Dr. Fazal Ur Rehman, Department Of Anatomy, Jawahar Lal NehruMedical College, AMU, Aligarh, INDIA. E-Mail: khanfazal660@gmail.com

Studies on the human skin microanatomy are few and contradictory. Using fetal skin of different age group, doingH & E staining followed by correlative light microscopy of serial tissue sections, and comparing it at differentfetal age, we studied the topographic microanatomy of the skin of human fetuses. Histomorphology was comparedfrom 8 weeks of gestation upto 30 weeks from last menstrual period (LMP). We found that epidermal differentiationbegins at 8 weeks of gestation. A single layer of epidermal cells covers embryos up to 9 weeks of gestation afterthe LMP. At 9 weeks, periderm is also visible and it’s called as a double layer stage. It is followed by appearanceof intermediate layer at 13 weeks. Budding cells are found only at 14 weeks. Hair follicles are visible at 16 weeks,whereas eccrine sweat glands appear at 20 weeks. Eccrine ducts are elongated and visible at 23 weeks. Coilingof the duct starts at 29th week. Thus, fetal age can be determined by studying the features of developing skin. Alsomany skin diseases show morphological changes in early fetal life. Congenital skin diseases can be predicted bythe knowledge of normal fetal skin development.KEY WORDS: Fetal Skin, Development, Histology (Microanatomy), Congenital, Skin diseases.

INTRODUCTION

International Journal of Anatomy and Research,Int J Anat Res 2017, Vol 5(1):3496-500. ISSN 2321-4287

DOI: https://dx.doi.org/10.16965/ijar.2016.508

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DOI: 10.16965/ijar.2016.508

*1 Associate Professor, Department of Anatomy, Jawahar Lal Nehru Medical College, AMU, Aligarh,INDIA.2 Department of Basic Medical Sciences, College of Applied Medical Sciences, KKU, Abha, KSA.

Received: 13 Dec 2016Peer Review: 15 Dec 2016Revised: None

Accepted: 06 Feb 2017Published (O): 28 Feb 2017Published (P): 28 Feb 2017

the skin of the foetus [3–5]. Identification ofthese age-related morphologic patterns allowsa definition of fetal age and offers backgroundinformation for detecting congenital skindiseases, such as ectodermal dysplasias,blistering diseases, and ichthyosis [6-8].Skin is a complex organ system in adult, acts asprotective barrier/ protective membrane of thebody, body temperature regulation, sensation,excretion, immunity, a blood reservoir, andsynthesis of vitamin D [9]. There are two typesof human skin, glabrous skin (non-hairy skin) andhair-bearing skin. Glabrous skin found on thepalms and soles, is grooved on its surface by

The objective of the study was to evaluate thehistological changes of fetal skin developmentat different stages of fetal development. Humanskin consists of a stratified cellular epidermisand an underlying dermis of connective tissue[1,2].Knowledge of the development of organs facili-tates the study of its adult anatomy; it also helpsto understand the developmental defects andstructural malformation. Beginning at 10th weeksand continuing until 30th weeks, the develop-ment of skin appendages is a sequence ofeasily recognizable histological patterns within

Int J Anat Res 2017, 5(1):3496-500. ISSN 2321-4287 3497

Fazal ur Rehman, Nazim Nasir. MICRO-MORPHOMETRIC STUDY OF SKIN IN DEVELOPING HUMAN FETUSES AND ITS CLINICAL RELEVANCE.

continuously alternating ridges and sulci, inindividually unique configurations known asdermatoglyphics. It is characterized by a thickepidermis divided into several well-markedlayers including a compact stratum corneum, bythe presence of encapsulated sense organswithin the dermis, and by a lack of hair folliclesand sebaceous glands. Hair-bearing skin(Fig. 3.1), on the other hand, has both hairfollicles and sebaceous glands but lacksencapsulated sense organs. Skin consists of twolayers derived from two germ layers: ectodermand mesoderm. The prospective epidermis,which originates from a surface area of the earlygastrula, and the prospective mesoderm, whichis brought into contact with the inner surface ofthe epidermis during gastrulation [10, 11].The mesoderm not only provides the dermis butis essential for inducing differentiation of theepidermal structures, such as the hair follicle inmammals [12]. The embryonic mesenchyme thatforms the connective tissue of the dermis.Sebaceous glands are first visible from the 13thto the 16th week of fetal development, asbulging off hair follicles. Sebaceous glandsdevelop from the same tissue that gives rise tothe epidermis of the skin. The sebaceous glandsof a human fetus secrete a substance calledvernix caseosa, a waxy, translucent white sub-stance coating the skin of newborns. After birth,activity of the glands decreases until there isalmost no activity during ages 2–6 years, andthen increases to a peak of activity duringpuberty, due to heightened levels of androgens.The neural crest also makes the pigment cellsto the skin. During the newborn period a largenumber of pathological conditions can causevesicles (small blisters), bullae (big blisters)pustules (yellow blisters), erosions (sores) andulcerations. Erythema toxicum neonatorum andmalaria are the most common skin conditionsof newborn.

length) at postmortem examination. The causesof abortion or fetal death included intradecidualhemorrhage with abruptio placentae, prematurerupture of membranes with chorioamnionitis,and pregnancy termination for localized fetalmalformations. Skin from gluteal regions weretaken for histology/ micro-morphometric study.Fetuses were collected from the departmentfetal lab. After measurement of the crown-rump(CR) for determining the age of fetuses, tissuespecimens were collected and fixed in 10%buffer formal saline, processed and sectionedinto 5–7 µm thick layers. The sections werestained with H&E method and observed bygraduated objective lens. To study the reticular,elastic and collagen fibers and mast cells,appropriate staining methods such as PAS,Verhoeff, Van Giesson and toluidine blue wereused, respectively. These tissue samples werestudied to establish the histological changesfrom the development of skin appendages, hairand apocrine & eccrine glands. Skin from otherparts of the body differs in the quantity of skinappendages and the time sequence of develop-mental events. Stages of skin developmentwould be 1–2 weeks ahead of schedule if skinfrom the neck was examined and 2 weeksbehind if skin from the thigh were used. Thisphenomenon reflects the overall developmentof mammalian embryos, which proceeds fromthe head pole to the caudal pole.

MATERIALS AND METHODS

Twenty-four human fetuses with known gesta-tional ages of 10-30 weeks were examined atautopsy. Gestational age derived from the lastmenstrual period (LMP) coincided with earlyultrasound measurements and developmentalindices (especially crown-rump length & foot

RESULTS

Assessment of skin samples allowed details ofthose features that are suddenly noticed andunderstood and can be used to determine thegestational age. This study showed that thedifferentiation of epidermis begins from the endof the second month. Based on the histologicsections, the stages of the gradual developmentof epidermis and skin appendages areillustrated to clarify the structures and theirnomenclature (Figure 2).Patterns of skin development are very easy toidentify as soon as one recognizes the morpho-logic differences between budding of basal cellsleading to hair follicles and budding leading toeccrine glands. The latter process is character-ized by slightly different cell morphology withinthe buds and the lack of mesenchymal

Int J Anat Res 2017, 5(1):3496-500. ISSN 2321-4287 3498

Fazal ur Rehman, Nazim Nasir. MICRO-MORPHOMETRIC STUDY OF SKIN IN DEVELOPING HUMAN FETUSES AND ITS CLINICAL RELEVANCE.

10 w: No appendages

14 w: Crowding of nuclei and budding of basal cells(

)

15 w: Accumulation of mesenchymal cells below hair bud ( )

16 w: Accumulation of mesenchymal cells below hair bud ( )

17 w: Elongation of hair follicles ( )

18 w: Sebaceous glands()

20 w: Hair shaft ( ) with eccrine duct ( )

25 w: Early coiling of eccrine ducts with lumen (

)

30 w: Coiling of eccrine glands ( )

condensation below the buds. A single layer ofepidermal cells covers embryos up to 9 weeksof gestation (after the LMP). From 9 to 13 weeks,two-layered skin is seen with a second, superfi-cial layer called periderm. From 13 weeks on,an intermediate layer is added and fetal skin isstratified, but still does not show appendages.Starting at 14 weeks, the developing skin showsbudding of cells of the basal layer into theunderlying mesenchyme. At 16 weeks, a corre-sponding proliferation of mesenchymal cells isseen just below the epidermal cell bud. Hairfollicles grow rapidly, and second and thirdgenerations of buds arise from the basal skinlayers. In the 18th week, hair shafts becomeclearly visible and sebaceous glands arerecognizable.Fetal skin at 20 weeks is characterized again bybudding of cells from the basal cell layer,resulting in the anlage of eccrine sweat glands.In contrast to the budding hair follicles, cells of

the eccrine sweat glands are more eosinophilic,cylindrical, and budding is not accompanied bya corresponding proliferation and condensationof the underlying mesenchymal tissue. At 23weeks, the eccrine gland ducts have elongatedand reached the level of transition of dermis tofatty tissue, and a lumen is hardly visible. At 24weeks, enlargement and kinking of the duct endoccur within the depth of the dermis, with theduct ends beginning to coil at 25 weeks. At 29or 30 weeks, eccrine sweat glands are coiled tosuch an extent that multiple transverse sectionscan be seen within the depth of the dermismelanocytes were appeared in 61–65 days offetal period in epidermis. The hair follicles wereseen as cell accumulations in epidermis thatprotruded toward dermis in the first half of thethird month. The hair follicles growth, sebaceousand sweat glands were appeared from thesecond half of the third month. They were quicklyincreased in the first half of the fourth month inall. The relationship between thickness ofepidermis and its cell layer numbers in all areaswere significant (P<0.05) and their correlationcoefficient?

DISCUSSION

Present study was carried out to see the epider-mal development in 1st & 2nd trimester humanfetuses. Analysis of epidermal development in2nd trimester shows the substantial developmentof hair follicle, separate the epidermis intofollicular and interfollicular region. In past fewyears, the use of fetal skin biopsies for prenataldiagnosis of severe inherited skin diseases hasshown the importance of the structural knowl-edge of normal human fetal skin. During the first10 weeks of gestation, the basic structure ofepidermis is built up. In the first 18 weeks ofgestation the most of the structural part andantigenic markers of epidermis are fully formed,both these are used for prenatal diagnosis forwhich fetal skin biopsy is usually carried.Epidermolysis bullosa lethalis and ichthyoticerythroderma have been diagnosed on fetal skinsamples at 16th to 20th week of gestation.Identification of structural abnormalities throughfetal skin biopsy in prenatal diagnosis is afeasible alternative to time consuming biochemi-cal analysis. In ichthyotic erythroderma, biopsy

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Fazal ur Rehman, Nazim Nasir. MICRO-MORPHOMETRIC STUDY OF SKIN IN DEVELOPING HUMAN FETUSES AND ITS CLINICAL RELEVANCE.

of fetal skin may be done to assess the histo-logic characteristics of the cells. Histologicalresults usually reveal hyperkeratotic skin cells,which ultimately give rise to a thick and hardskin layer. The developing fetus has the abilityto heal wounds by regenerating normal epider-mis and dermis with restoration of the extracel-lular matrix (ECM) architecture, strength, andfunction. In contrast, adult wounds heal withfibrosis and scar.Scar tissue remains weaker than normal skin withan altered ECM composition. Despite extensiveinvestigation, the mechanism of fetal woundhealing remains largely unknown. As a result ofresearch in past, we do know that early ingestation, fetal skin is developing at a rapid paceand the ECM is a loose network facilitatingcellular migration. Wounding in this uniqueenvironment triggers a complex cascade oftightly controlled events culminating in ascarless wound phenotype of fine reticularcollagen and abundant hyaluronic acid. Compari-son between postnatal and fetal wound healinghas revealed differences in inflammatoryresponse, cellular mediators, cytokines, growthfactors, and ECM modulators. Investigation intocell signaling pathways and transcriptionfactors has demonstrated differences in second-ary messenger phosphorylation patterns andhomeobox gene expression. Further researchmay reveal novel genes essential to scar lessrepair that can be manipulated in the adultwound and thus ameliorate scar. The differenceswere found to be small but consistent with theages of the fetuses.

gestational age of a fetus. However, in manycases, this information is not given or theaccuracy of the age given is doubtful becauseof severe growth, retardation or organ hypopla-sia then assessing gestation age from histol-ogy of fetal skin is done. This data have poten-tial relevance to prenatal diagnosis of inher-ited skin disease. From amniocentesis and/orfetal biopsy specimens; the present study offetal epidermal surface will allow one topredict the types of skin-derived cells thatshould be present in the amniotic fluid at a givenage, and to evaluate a fetal biopsy from skinand be confident that it is an accurate index offetal skin development, age and status ingeneral.

CONCLUSION

Skin development is continuous process butsome noticeable and discrete patterns arestrongly related to fetal age and are easy torecognize congenital primary skin diseases havea great impact on developing skin morphology[13-15]; conditions such as restrictive dermopa-thy, ectodermal dysplasia, and different formsof epidermolysis bullosa show abnormalitiesalready in the early stages of fetal development.Recognition of the early manifestations ofcongenital skin diseases is possible only withexact knowledge of normal histology. In post-mortem examination the clinician usually gives

Conflicts of Interests: None

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Fazal ur Rehman, Nazim Nasir. MICRO-MORPHOMETRIC STUDY OF SKIN IN DEVELOPING HUMAN FETUSES AND ITS CLINICAL RELEVANCE.

How to cite this article:Fazal ur Rehman, Nazim Nasir. MICRO-MORPHOMETRIC STUDY OFSKIN IN DEVELOPING HUMAN FETUSES AND ITS CLINICAL RELEVANCE.Int J Anat Res 2017;5(1):3496-3500. DOI: 10.16965/ijar.2016.508

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[13]. Rodeck CH, Eady RAJ, Gosden CM. Prenatal diagno-sis of epidermolysis bullosa lethalis. Lancet1980;i:949-52.

[14]. Golbus MS, Sagebiel RW, Filly RA, Gindhart TD, HallJG. Prenatal diagnosis of congenital bullous ich-thyosiform erythroderma (epidermolytic hyperkera-tosis) by fetal skin biopsy. N Engl J Med 1980;302:93-5.

[15]. Elias S, Mazur M, Sabbagha R, Esterly NB, SimpsonJL. Prenatal diagnosis of harlequin ichthyosis. ClinGenet 1980;17:275-80.