Prenatal hair development: Implications for drug exposure determination

doi:10.1016/j.forsciint.2009.12.024

Forensic Science International

Volume 196, Issues 1–3, 20 March 2010, Pages 27-31

https://doi.org/10.1016/j.forsciint.2009.12.024 Get rights and content

Abstract

Neonatal hair is a clinically important toxicological matrix, as it allows determination of in utero drug exposure. This paper serves to review the physiological development of the hair follicle and hair production during fetal life. An understanding of the mechanisms and timing of hair development in the prenatal period is critical to effectively assessing the time window of exposure determination associated with toxicological analysis of neonatal hair.

Section snippets

Origins of hair follicle development

Hair follicle development occurs as a result of ectodermal and mesodermal interactions during epidermal development [3], [4]. The majority of the hair follicle structure is comprised of ectodermal derivatives, however the dermal papilla, located at the base of the follicle is derived from the mesodermal mesenchyme of the dermis; the dermis itself being originated from the paraxial mesoderm via the dorsolateral aspect of the somite (dermomyotome) [5].

Melanocytes, the cells responsible for skin

Hair follicle initiation and structural development

Hair follicle development begins with the formation of a placode in the epidermal ectoderm consisting of condensed, elongated epidermal keratinocytes [3]. At approximately the 8th week of development, hair follicles begin to appear as a condensed proliferation of epidermal cells budding down into the mesenchymal dermal region adjacent to the ectoderm (see Fig. 1) [4], [11]. Multiple signaling molecules are proposed to be involved in stimulating invagination of the hair bud. Increases in

The production of hair and follicular growth cycle

Hair follicles are unique organs, in that they continually cycle through periods of activity and degeneration, essentially renewing themselves perpetually while local hair production continues. The three stages of the follicular life cycle are known as the anagen phase (hair production), catagen phase (involution/degeneration of the lower follicle), and the telogen phase (‘resting’ phase) ultimately resulting in the loss of the produced hair fiber (Fig. 1) [11], [15], [32]. All hair follicles

Patterns and waves of prenatal hair growth

The initiation of scalp hair production in utero occurs in waves evident by the developmental stage of the follicle demonstrated at birth. In the neonate, follicles in the frontal and parietal regions of the scalp (Fig. 4) are already converting to the telogen phase. Anagen-phase follicles cover the occipital region of the scalp, with catagen/telogen progression occurring sometime after the 8th and usually before the 12th post-natal week [8].

The morphology of hair fibre and duration of the

Summary

Initial hair production begins around the 10th week of development with hair first appearing transcutaneously around 16 weeks. By the 20th week the entire scalp is covered with anagen phase hair. These follicles undergo their first life cycle and hair production ceases with the initiation of a short catagen/telogen phases between the 24th and 28th developmental week. Scalp hair fibres present at birth, therefore, reflect metabolic activity occurring after the 28th week of prenatal development

References (48)

E.M. Ostrea et al.
Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides
Environ. Res.
(2009)
R. Paus et al.
Transforming growth factor-beta receptor type I and type II expression during murine hair follicle development and cycling
J. Invest. Dermatol.
(1997)
D.W. Smith et al.
Scalp hair patterning as a clue to early fetal brain development
J. Pediatr.
(1973)
U. Gat et al.
De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin
Cell
(1998)
K.D. Kaufman
Androgen metabolism as it affects hair growth in androgenetic alopecia
Dermatol. Clin.
(1996)
Y. Mishima et al.
Embryonic development of melanocytes in human hair and epidermis. Their cellular differentiation and melanogenic activity
J. Invest. Dermatol.
(1966)
D.K. Kim et al.
The appearance, density, and distribution of Merkel cells in human embryonic and fetal skin: their relation to sweat gland and hair follicle development
J. Invest. Dermatol.
(1995)
A.C. Gilliam et al.
The human hair follicle: a reservoir of CD40+ B7-deficient Langerhans cells that repopulate epidermis after UVB exposure
J. Invest. Dermatol.
(1998)
D.M. Danilenko et al.
Growth factors and cytokines in hair follicle development and cycling: recent insights from animal models and the potentials for clinical therapy
Mol. Med. Today
(1996)
F. Pragst et al.
State of the art in hair analysis for detection of drug and alcohol abuse
Clin. Chim. Acta
(2006)

M.H. Hardy

The secret life of the hair follicle

Trends Genet.

(1992)

L. Jones

Hair structure anatomy and comparative anatomy

Clinics Dermatol.

(2001)

D.F. Orwin

The cytology and cytochemistry of the wool follicle

Int. Rev. Cytol.

(1979)

L.N. Jones et al.

The role of 18-methyleicosanoic acid in the structure and formation of mammalian hair fibres

Micron

(1997)

L.N. Jones et al.

Formation of surface membranes in developing mammalian hair fibres

Micron

(1994)

T. Gray et al.

Bioanalytical procedures for monitoring in utero drug exposure

Anal. Bioanal. Chem.

(2007)

R. Schmidt-Ullrich et al.

Molecular principles of hair follicle induction and morphogenesis

Bioessays

(2005)

K. Moore et al.

The Developing Human: Essentials of Embryology and Birth Defects

(1998)

M. Wiley et al.

MSC1008Y: Advanced Human Embryology

(2009)

M. Sieber-Blum et al.

Epidermal neural crest stem cells (EPI-NCSC) and pluripotency

Stem Cell Rev.

(2008)

A. Mancini

Structure and function of the newborn skin

S.A. Furdon et al.

Scalp hair characteristics in the newborn infant

Adv. Neonatal Care

(2003)

M. Sieber-Blum et al.

The adult hair follicle: cradle for pluripotent neural crest stem cells

Birth Defects Res. C: Embryol. Today

(2004)

M. Sieber-Blum et al.

Pluripotent neural crest stem cells in the adult hair follicle

Dev. Dyn.

(2004)

Cited by (42)

Anatomy and physiology of human hair
2023, Toxicologie Analytique et Clinique
Souvent qualifié de « mini-organe », le cheveu humain s’avère d’une extrême complexité. D’un point de vue anatomique, le cheveu adulte est divisé en deux zones distinctes : la tige, composée de cellules épithéliales anucléées et kératinisées, visibles à la surface du scalp, et la racine, ou follicule pileux, qui forme avec ses annexes, les glandes sudorales et sébacées, et le muscle arrecteur, l’unité pilo-sébacée. Sur le plan physiologique, le follicule présente un cycle continu de croissance et de régression contrôlé par un environnement nécessitant des compartiments de cellules souches progénitrices ainsi que des voies de signalisation complexes. Pour parvenir à une telle collaboration entre le follicule et son environnement, une morphogenèse sophistiquée est nécessaire au cours du développement embryonnaire. Le développement du cheveu commence vers la 8^e semaine de vie et se compose de trois phases, l’induction, l’organogenèse et la cytodifférenciation. Ce processus nécessite une interaction étroite entre l’ectoderme et le mésoderme sous-jacent par l’intermédiaire de facteurs de croissance, de cytokines, de neuropeptides, de neurotransmetteurs et d’hormones. Les premiers cheveux émergent par vagues successives et présentent des caractéristiques morphologiques et des modalités de croissance différentes de celles du cheveu terminal, qui apparaît entre 12 et 18 mois. La compréhension de ces phénomènes est essentielle pour appréhender les mécanismes d’incorporation des xénobiotiques dans les cheveux, ainsi que les difficultés d’interprétation des concentrations, en particulier dans la petite enfance.
Often qualified as a mini-organ, human hair presents a complex functioning. From an anatomical perspective, adult hair is divided into two parts: the hair shaft, composed of dead, fully keratinized epithelial cells visible on the surface of the scalp, and the root, which includes the hair follicle and its appendages, the sweat and sebaceous glands as well as the arrector muscle, to form the pilosebaceous unit. The follicle presents a continuous cycle of growth and regression, controlled by an environment requiring surrounding niches for hair follicle stem cells and various signaling pathways. To achieve such a complex organization between hair follicles and surrounding environment, sophisticated morphogenesis is required during embryonic development. Indeed, hair development begins around the 8th week of development and consists of three phases, induction, organogenesis and cytodifferentiation. This process requires close interaction between the ectoderm and the mesoderm via growth factors, cytokines, neuropeptides, neurotransmitters, and hormones. The first hair emerges in successive waves and present different morphological and growth characteristics from the terminal hair, which appears between 12 and 18 months. Comprehension of these phenomena is essential to understand the mechanisms of drug incorporation into hair, as well as the difficulties of interpretation of the concentrations, particularly in the early childhood.
Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit
2023, Environmental Research
Due to adverse health effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted, and gradually replaced by alternative plasticizers (APs). Up to this date, urine was the sole matrix studied for plasticizer exposure in neonates hospitalized in the neonatal intensive care unit (NICU), a population highly vulnerable to toxic effects of plasticizers. The primary aim of this study was to assess simultaneous measurement of phthalate and AP metabolites in neonatal scalp hair. In addition, we aimed to use this matrix to investigate exposure of premature neonates to plasticizers during their stay in the NICU.
Hair samples in this study were collected from premature neonates and their mothers included in a prospective birth cohort study in a tertiary NICU at the Antwerp University Hospital (UZA), Belgium. Samples from premature neonates (n = 45) and their mothers (n = 107) as well as from control neonates (n = 24) and mothers (n = 29) were analyzed using liquid-chromatography coupled to tandem mass spectrometry.
This is the first study reporting metabolites of phthalate and alternative plasticizers in neonatal hair samples as biomarkers for exposure to these plasticizers. Results showed that hair sampled from premature neonates after a NICU stay contained significantly higher metabolite concentrations of both phthalates (DEHP, DiBP, and DnBP; 9.0–2500, 9.3–2200, and 24.7–5300 ng/g), and alternative plasticizers (DEHA, DEHT, and TOTM; 38.8–3400, 127.5–5700, and 10.8–8700 ng/g) – when compared to healthy control neonates. Besides, DEHP and DEHT metabolite concentrations were significantly higher than in hair sampled from adult populations. In addition, prolonged NICU exposure to non-invasive respiratory support devices and gastric tubes was correlated with increased concentrations in hair samples, indicating accumulation of plasticizers in this alternative matrix.
In conclusion, our data indicate that preterm neonates are still highly exposed to phthalate and alternative plasticizers during NICU stay, despite the EU Medical Devices Regulation.
Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism
2023, Journal of Steroid Biochemistry and Molecular Biology
Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n = 42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11β-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11βHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.
Fetal exposure to organic contaminants revealed by infant hair: A preliminary study in south China
2023, Environmental Pollution
Citation Excerpt :
These results suggest that p,p'-DDE in infant hair originates from the predominated maternal-fetal transmission of p,p'-DDE rather than the maternal metabolism of p,p'-DDT. Between developmental weeks 24–28, fetal follicles enter the catagen phase, followed by telogen stages, and then shed to undergo their second life cycle (Gareri and Koren, 2010). Consequently, infant hair OC levels in full-term neonates are thought to provide an index of OC exposure from week 28 of pregnancy to birth (roughly in the last trimester).
Fetal exposure to multiple organic contaminants (OCs) is a public concern because of the adverse effects of OCs on early life development. Infant hair has the potential to be used as an alternative matrix to identify susceptible fetuses, owing to its reliability, sensitivity, and advantages associated with sampling, handling, and ethics. However, the applicability of infant hair for assessing in utero exposure to OCs is still limited. In this study, 57 infant hair samples were collected in Guangzhou, South China, to evaluate the levels and compositions of typical OCs in the fetus. Most of the target OCs were detected in infant hair, with medians of 144 μg/g, 17.7 μg/g, 192 ng/g, 46.9 ng/g, and 1.36 ng/g for phthalate esters (PAEs), alternative plasticizers (APs), organophosphorus flame retardants (OPFRs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs), respectively. Meanwhile, paired maternal hair (0–9 cm from the scalp) was collected to examine the associations between maternal and infant hair for individual compounds. Low-brominated PBDEs tended to deposit in infant hair, with median concentrations approximately two times higher than those in maternal samples. Levels of PBDEs and 4,4′-dichlorodiphenyldichloroethylene (p,p'-DDE) in paired maternal and infant hair showed strong positive correlations (p < 0.05), while most plasticizers (PAEs and APs) were poorly correlated between paired hair samples. Exposure sources were responsible for the variation in correlation between OC levels in the paired infant and maternal samples. Crude relationships between fetal exposure to OCs and birth size were examined using the Bayesian kernel machine regression (BKMR) model. BDE-28 was found to be adversely associated with the birth size. This study provides referential information for evaluating in utero exposure to OCs and their health risks based on infant hair.
An update on stem cells applications in burn wound healing
2021, Tissue and Cell
Burn wounds have proven to be capable of having a long lasting devastating effects on human body. Conventional therapeutic approaches are not up to the mark as they are unable to completely heal the burn wound easily and effectively. Major pitfalls of these treatments include hypertrophic scarring, contracture and necrosis. Presence of these limitations in the current therapies necessitate the search for a better and more efficient cure. Regenerative potency of stem cells in burn wound healing outweigh the traditional treatment procedures. The use of multiple kinds of stem cells are gaining interest due to their enhanced healing efficiency. Distinctions of stem cells include better and faster burn wound healing, decreased inflammation levels, less scar progression and fibrosis on site. In this review, we have discussed the wound-healing process, present methods used for stem cells administration, methods of enhancing stem cells potency and human studies. Pre-clinical and the clinical studies focused on the treatment of thermal and radiation burns using stem cells from 2003 till the present time have been enlisted. Studies shows that the use of stem cells on burn wounds, whether alone or by the help of a scaffold significantly improves healing. Homing of the stem cells at the wound site results in the re-epithelialization, angiogenesis, granulation, inhibition of apoptosis, and regeneration of skin appendages together with reduced infection rate in the human studies. Several studies on animals have shown that stem cells can effectively promote wound healing. Although more research is needed to find out the effectiveness of this treatment in patients with severe burn wounds.
Hair analysis of more than 140 families with drug consuming parents. Comparison between hair results from adults and their children
2019, Forensic Science International
Hair samples from children are frequently analyzed in order to characterize their endangerment in a drug using environment. However, the interpretation of the results remains difficult because of lacking data for comparison. In this study, hair samples from families with drug consuming parents were analyzed for illegal and selected medical drugs and the results were evaluated concerning a relationship between findings of parents and children depending on kind of drug, age and gender of children as well as maternal or paternal drug concentrations in hair.
In an ongoing social supporting project for families with underage children and drug consuming parents, hair samples were analyzed since 2011 for methadone, opiates and opioid analgesics, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines by LC–MS/MS with LOQs ≈ 0.01 ng/mg. From the data pool of more than 1300 individuals, 100 families with results for one or both parents and one to five children, 30 families with results only for both parents, and 11 families with results only for 2–4 children were selected. Fifty eight of these 141 families were repeatedly tested (altogether 251 family tests).
One to 5 drugs were detected in 239 (95.2%) of the family tests with highest occurrence of cocaine (79.7%) and THC (50.2%). According to the concentrations of the tested persons, the most probable drug users were the mother (25%), the father (24%), both parents (16%), or were not tested (30%). Within the families, there was an agreement of the detected drugs between parents and children of 47.8%, between both parents of 36.1%, and between children of 42.3%. For parents with hair concentrations in the typical range of regular drug use, the drug was detected in children hair with the following frequency: methadone 65.5%, heroin (6-AM) 63.6%, cocaine 92.1%, amphetamine 80%, MDMA 42.9% and THC 67.4% with higher percentage for younger children. The agreement for medical drugs (benzodiazepines 7.7%, synthetic opioids 8.7%, diphenhydramine 7.1%) was much lower suggesting voluntary administration or intake. Despite the strong variation of the data, clear trends were found that the child/parent drug concentration ratio decreases with increasing children age and is higher for boys than for girls.
The comparison of hair results within families gives a deeper insight in the drug situation, often enables the identification of the drug user and is helpful for social and legal decisions to improve the conditions of the children.

View all citing articles on Scopus

View full text

Prenatal hair development: Implications for drug exposure determination

Abstract

Section snippets

Origins of hair follicle development

Hair follicle initiation and structural development

The production of hair and follicular growth cycle

Patterns and waves of prenatal hair growth

Summary

Environ. Res.

J. Invest. Dermatol.

J. Pediatr.

Cell

Dermatol. Clin.

J. Invest. Dermatol.

J. Invest. Dermatol.

J. Invest. Dermatol.

Mol. Med. Today

Clin. Chim. Acta

Trends Genet.

Clinics Dermatol.

Int. Rev. Cytol.

Micron

Micron

Bioanalytical procedures for monitoring in utero drug exposure

Anal. Bioanal. Chem.

Molecular principles of hair follicle induction and morphogenesis

Bioessays

The Developing Human: Essentials of Embryology and Birth Defects

MSC1008Y: Advanced Human Embryology

Epidermal neural crest stem cells (EPI-NCSC) and pluripotency

Stem Cell Rev.

Structure and function of the newborn skin

Scalp hair characteristics in the newborn infant

Adv. Neonatal Care

The adult hair follicle: cradle for pluripotent neural crest stem cells

Birth Defects Res. C: Embryol. Today

Pluripotent neural crest stem cells in the adult hair follicle

Dev. Dyn.