Section I: Introduction
Surber C, Elsner P, Farage MA (eds): Topical Applications and the Mucosa.
Curr Probl Dermatol. Basel, Karger, 2011, vol 40, pp 9–19
Morphology and Physiological Changes of Genital
Skin and Mucosa
Miranda A. Faragea ⭈ Howard I. Maibachb
a
Feminine Care Clinical Sciences, Procter and Gamble Company, Cincinnati, Ohio, and bDermatology Department, University of
California School of Medicine, San Francisco, Calif., USA
Abstract
The morphology and physiology of both the vulva and
vagina undergo characteristic age-related changes over
a lifetime. At birth, these tissues exhibit the effects of
residual maternal estrogens. During puberty, the vulva
and vagina mature under the influence of adrenal and
gonadal steroid hormones. During the reproductive
years, the vagina responds to ovarian steroid hormone
cycling, and both tissues adapt to the needs of pregnancy
and delivery. Following menopause, the vulva and vagina
atrophy. A rise in the prevalence of incontinence among
older women increases the risk of vulvar and perineal der-
matitis. This chapter covers the morphology and physiol-
ogy of the genital area from infancy to old age.
Copyright © 2011 S. Karger AG, Basel
The morphology and physiology of the vulva and
vagina change over a lifetime. The most salient
changes are linked to puberty, the menstrual cy-
cle, pregnancy and menopause. The cutaneous
epithelia of the mons pubis, labia and clitoris orig-
inate from the embryonic ectoderm and exhibit a
keratinized, stratified structure similar to skin at
other sites. The mucosa of the vulvar vestibule,
which originates from the embryonic endoderm,
is nonkeratinized. The vagina, derived from the
embryonic mesoderm, is responsive to estrogen
cycling. At birth, the vulva and vagina exhibit the
effects of residual maternal estrogens. During pu-
berty, the vulva and vagina acquire mature char-
acteristics in a sequential fashion in response to
adrenal and gonadal maturation. A trend to ear-
lier pubertal onset has been observed in Western
developed countries. In women of reproduc-
tive age, the vaginal mucosa responds to steroid
hormone cycling, exhibiting maximal thickness
and intracellular glycogen content at mid-cycle.
Vulvar skin thickness remains unchanged but
menstrual-cycle-associated changes in ortho-
and parakeratosis occur at the cytological level.
The vulva and vagina further adapt to the needs
of pregnancy and delivery. After menopause, tis-
sue atrophy ensues. Postmenopausal changes in
skin barrier function, skin hydration and irritant
susceptibility have been observed on exposed skin
but not on the vulva. Nevertheless, older women
with incontinence are at increased risk for devel-
oping incontinence dermatitis. A combination of
factors, such as tissue atrophy, slower dissipation
of excess skin hydration, shear forces associated
with limited mobility and lower tissue regenera-
tion capacity increase the risk of morbidity from
incontinence dermatitis in older women. This
chapter covers the morphology and physiology of
Table 1. Morphological and physiological changes in genital skin and mucosa from infancy to old age (reproduced from Farage
et al. [1] and Farage and Maibach [2])

Life stage Pertinent physiology Vulvar characteristics Vaginal features

(approximate age*)

Newborn Effects of residual, Plump labia majora Stratified squamous epithelium

(birth to 1 month old) transplacental maternal
estrogens
Well-developed labia minora
Immature hair follicles and
sebaceous glands
high in glycogen content
Lactic-acid-producing microbes
colonize the vagina shortly after
birth
White or blood-tinged vaginal
discharge may be present [3]

Early childhood Lack of stimulation by Mons pubis and labia majora The vaginal epithelium thins, is
(1 year to 8 years of adrenal or gonadal steroid lose fat less stratified and has a low
age) hormones Benign labial adhesions, if glycogen content
present, normalize without Vaginal pH is neutral or alkaline
treatment [4] Prevalence of lactic-acid-
producing microbes decreases
[5]

Puberty Adrenal and gonadal
(8–15 years of age) maturation ensues.
Secondary sex characteristics
are acquired, and
menstruation begins [6]
Subcutaneous fat is deposited
in the mons pubis and labia
majora
The vulvar epithelium thickens
The labia minora and clitoris
become more prominent
Pubic hair emerges
The vaginal epithelium thickens
and stratifies
Cyclic changes in intracellular
glycogen content ensue
Cervicovaginal secretions are
produced
Prevalence of lactic-acid-
producing microbes rises [5]

Reproductive years The menstrual cycle The morphology of the vulva is
(menarche, approx. mature
12 years until Vulvar skin thickness remains
perimenopause) constant throughout the
menstrual cycle [7]
Parakeratosis of the vulvar
stratum corneum rises at
mid-cycle [7, 8]
Vaginal epithelial thickness,
parakeratosis and glycogen
content rise at mid-cycle [7, 8]
Lactic-acid-producing microbes
are numerically dominant in
healthy women [9, 10]
Menstrual cyclicity becomes
established [11, 12]
Cervicovaginal secretions
become thicker, clearer and more
elastic prior to ovulation

Pregnancy Blood volume increases; the
menstrual cycle ceases
during gestation
Hair may darken along the
midline of the abdomen
Increased blood flow heightens
vulvar coloration
Susceptibility to vulvar varicose
veins increases [13]
Flattening of the fourchette
and perineal trauma occur
during delivery
Connective tissue relaxes and
vaginal muscle fibers thicken
The risk of Candida infection
increases [14]
Following delivery, the
morphology and dimensions of
the vaginal tract are
reestablished

10 Farage · Maibach
Table 1. Continued

Life stage Pertinent physiology Vulvar characteristics Vaginal features

(approximate age*)
Postmenopause Follicular function and the
(1 year following final menstrual cycle cease; the
menstrual period, prevalence of urinary and
approx. average 50 fecal incontinence rises;
years old) physical health, immune
function, tissue regeneration
capacity and cognition may
be compromised with
increasing age
Pubic hair becomes sparse
Subcutaneous fat is lost
Vulvar tissue atrophies
The risk of perineal dermatitis
rises in older women with
incontinence
The vaginal epithelium atrophies
Cervicovaginal secretions
become sparse
Vaginal pH rises; colonization by
enteric microflora may rise
Atrophic vaginitis is common

*The age definition of each stage is approximate due to interindividual variations.

the genital area from infancy to old age and has
been reviewed in Farage et al. [1] and Farage and
Maibach [2]. A summary of these changes can be
found in table 1.
Embryonic Derivation and Epithelial Structure
size and organelle density as they migrate upward
from the generative basal layer, but do not form
clearly demarcated strata as observed in the skin
(fig. 1b). The vagina, of mesodermal origin, has
nonkeratinized squamous epithelium that is re-
sponsive to ovarian steroid hormone cycling [7].

The lower urogenital tract is the only portion of
the female anatomy derived from all 3 embryolog-
ical layers (ectoderm, endoderm and mesoderm)
[15]. Like skin at other anatomical sites, the skin
of the mons pubis, the labia, the clitoris and the
perineum, derived from the embryonic ectoderm,
has a keratinized, stratified squamous structure
with sweat glands, sebaceous glands and hair fol-
licles (fig. 1a). Cutaneous thickness and degree of
keratinization are relatively high on the mons pu-
bis and labia majora, but decrease over the anterior
portions of the clitoris and in going from the out-
er surface to the inner surface of the labia minora
[16]. The mucosa of the vulvar vestibule is the only
portion of the female genital tract of endodermal
origin [17]. Its superficial stratum is nonkerati-
nized, and differentiation of the inner layers is in-
distinct: loosely packed, polyhedral cells alter in
Infancy and Early Childhood
The genitals of the newborn exhibit the effects
of residual maternal estrogens. At birth, the labia
majora appear plump, and the labia minora are
well developed. The vaginal introitus is visible,
but the urethral opening less easily discerned. The
vaginal mucosa is glycogen rich. It becomes colo-
nized with lactic-acid-producing microbes, such
as Lactobacillus species, within the first 24 h of
birth [6]. A physiological, white, mucoid vaginal
discharge is present, which may become tinged
by slight withdrawal endometrial bleeding as the
concentration of residual maternal estrogen falls
[3, 18].
These estrogenic effects dissipate by the fourth
postnatal week. The vaginal epithelium loses its
stratification and glycogen content, becoming

Morphology and Physiological Changes of Genital Skin and Mucosa 11

 Intercellular material -
high lipid content
Keratinized
Stratum
corneocyte
corneum
Stratum
granulosum

Desmosome Pyknotic nucleus

Stratum Stratum
spinosum superficiale

Sweat duct
Stratum
Stratum basale/ spinosum
parabasale Desmosome
Basement
membrane Stratum basale/
parabasale
Dermis
Subepithelial
Basement
Sweat tissue
membrane
glands Sebaceous glands
Hair follicle
a b

Fig. 1. Vulvar epithelial structure. Adapted with permission from Farage and Maibach [2]. a Vulvar skin. b Mucosa.

much thinner. The vaginal pH becomes neutral Puberty

or alkaline, presumably because of a relative defi-
ciency of acid-producing vaginal microbes [5, 19,
20]. Vulvar skin thickness drops, and the mons
pubis and labia majora lose some of the subcuta-
neous fat present at birth [16, 21, 22]]. Although
the full complement of vulvar hair follicles and
sebaceous glands is thought to be present from
birth, these structures do not mature until the ad-
renal glands are activated at puberty. The prepu-
bescent labia minora have barely discernible vel-
lus hair follicles that are lost at puberty when the
follicles of the labia majora and mons pubis termi-
nally differentiate [21].
Labial adhesions may occur between the ages
of 2 months and 2 years, creating a flat vulvar ap-
pearance. This benign condition is due to a lack
of estrogen and normalizes without treatment.
Should the condition interfere with urinary flow,
topical estrogen treatment promotes separation of
the labia [4].
Pubertal changes in the vulva and vagina are in-
duced by adrenal and gonadal maturation. Puberty
generally begins between the ages of 8 and 13
years. Physical changes associated with puberty
are an accelerated growth rate, the appearance of
pubic hair (pubarche), the appearance of axillary
hair, breast development (telarche) and the on-
set of menstruation (menarche). The timing and
stages of development of secondary sex charac-
teristics were first defined in the seminal study of
192 girls in a British orphanage by Marshall and
Tanner [23].
Maturation of the adrenal glands and androgen
secretion (adrenarche) begin at about the age of
6, approximately 2 years before pituitary-gonadal
maturation and the production of ovarian steroid
hormones (gonadarche). Because adrenarche and
gonadarche proceed independently, the appear-
ance of pubic hair does not provide information

12 Farage · Maibach
1 2
Fig. 2. Tanner stages of pubic hair development. Reproduced from Farage et al. [1] and Farage and Maibach [2].
about pituitary-ovarian maturation. Pubic hair
development, elicited by androgens, proceeds in
5 stages [23] (fig. 2):
• stage 1: no pubic hair;
• stage 2: sparse hair appears on the labia majora
and the mons pubis along the midline;
• stage 3: the thickness and coarseness of the
hair increases, with coverage of the lobes of the
labia majora and increased lateral growth from
the midline of the mons pubis;
• stage 4: hair growth increases such that only the
upper lateral corners of the mature triangular
configuration are deficient;
• stage 5: adult pattern, attained between the
ages of 12 and 17 years, with a characteristic
horizontal upper margin on the mons pubis
just above the limit of the genitofemoral folds,
and hair coverage extending from the labia to
the upper aspects of the thighs.
Gonadal maturation usually occurs during the
2 years preceding menarche. During the matura-
tion process, follicular development causes estro-
gen production to rise. The vaginal epithelium
thickens and intracellular glycogen production
begins. The cervix and vagina increase in size, the
vaginal fornices develop, cervicovaginal secretions
are produced, and vaginal fluid becomes acidic.
Vulvar morphology also matures at this time.
Fat deposition occurs in the mons pubis and la-
bia majora. The vulvar epithelium increases in
thickness [16], labial skin becomes rugose, the
clitoris becomes more prominent, the vestibu-
lar glands become active, the introitus increases
Morphology and Physiological Changes of Genital Skin and Mucosa
3 4 5
in diameter, and the urethral orifice is more
discernible.
Breast development, influenced by estrogens, is
also described by 5 Tanner stages, from no develop-
ment (stage 1) to the mature adult breast (stage 5)
[23]. Menarche occurs near the end of the Tanner
sequence of breast changes, typically sometime
between the ages of 11 and 15 years [6]. The mean
age of menarche worldwide lies between 12 and
13 years [24]. The sequence from first appearance
of pubic hair to breast development and menar-
che takes about 4 years. Normative menstrual cy-
cle length is established by the sixth gynecological
year (i.e. the sixth year following menarche), usu-
ally at a chronological age of 19 or 20 [11, 12].
Idiopathic Precocious Puberty
Historically, puberty had been defined as preco-
cious in girls when secondary sex characteristics
(particularly breast development) appeared prior
to the age of 8. However, an apparent advance in the
age of onset of pubertal changes has been observed
in the USA and in girls from developing countries
who have migrated to Western Europe for foreign
adoption (reviewed in Parent et al. [25]). Two large
studies in the USA found that pubertal signs may
appear before the age of 8, especially in African-
American compared to Caucasian girls (reviewed
in Anderson et al. [26], Herman-Giddens et al.
[27] and Sun et al. [28]). Between the 1970s and
1990s, the average age of menarche in the USA fell
from 12.75 to 12.54 years [26].
13
 Controversy surrounds the clinical significance
of these findings. Most cases of early pubertal devel-
opment are idiopathic [29, 30] and probably do not
represent precocious puberty unless bone matura-
tion and developmental characteristics are so ac-
celerated that diminished adult height is likely [29].
However, because true endocrine pathology may
be overlooked if early pubertal signs are dismissed,
a vigilant longitudinal follow-up of girls with ear-
ly pubertal onset is advised [31]. Several risk fac-
tors, including genetics [32], low birth weight [33,
34], higher body mass index [26, 35–38] and ex-
posure to endocrine disruptors [39–42], have been
statistically linked to early onset of pubertal signs.
However, the causative biological mechanisms for
this phenomenon are still unknown.
Reproductive Years
During the reproductive years, changes in the vul-
va and vagina are linked to the menstrual cycle
and pregnancy. Physiological changes during the
menstrual cycle have been recently reviewed in
Farage et al. [43].
Effects of the Menstrual Cycle
Vulvar epithelial thickness is at its highest in the
reproductive years. Vulvar skin thickness remains
constant over the menstrual cycle, but its surface
cells are predominantly orthokeratotic (lacking
nuclei) at the beginning and end of the cycle, and
increasingly parakeratotic (bearing a degener-
ated nucleus) at mid-cycle [8]. These cytological
changes are thought to be mediated by estrogen:
for example, parakeratosis of vulvar epithelial
cells is rare in postmenopausal women but rises
dramatically in this group in response to systemic
estrogen supplementation [8].
The vaginal mucosa is sensitive to ovarian
steroid hormone cycling. Estrogen stimulation
causes the thickness, glycogen content and par-
akeratosis of the vaginal epithelium to peak at ap-
proximately mid-cycle [7].
14
Vaginal pH rises during menstruation [44],
and the current understanding of the impact of
the menstrual cycle on the microbial ecology of
the vagina from infancy to after the menopause
has been reviewed by Farage et al. [20]. Studies
using traditional culture techniques suggest that
Lactobacillus species predominate in the vaginal
flora of healthy women and that their cell densi-
ties remain relatively constant over the menstrual
cycle [9]. However, culture techniques typically
identify only the most readily cultivated microbi-
al populations, which may represent but a subset
of the extant community. Emerging data obtained
by analysis of total microbial community DNA
indicate that lactic-acid-producing species such
as Atopobium, Megasphaera and Leptotrichia,
rather than Lactobacillus, are numerically dom-
inant in some women [10]. Consequently, gen-
era besides Lactobacillus may contribute to the
acidity of the vaginal tract, but the impact of the
menstrual cycle on these genera is still to be in-
vestigated [20].
Effects of Pregnancy and Delivery
During pregnancy, an increase in total blood vol-
ume heightens the coloration of the vulva and va-
gina. The connective tissue of the vulva, vagina
and perineum relaxes, and the muscle fibers of the
vaginal wall increase in size in preparation for de-
livery. Progesterone elevates venous distensibility,
which may cause varicose veins in the vulva [13].
Pregnancy is associated with a 10- to 20-fold in-
crease in the prevalence of vulvovaginal candidi-
asis [14, 20].
During delivery, the perineal and vaginal mus-
culature relaxes and the vaginal rugae flatten to
allow expansion of the vaginal tract, accommo-
dating passage of the newborn infant. Injury to
the perineum may occur spontaneously or be-
cause of episiotomy. After delivery, the vaginal in-
troitus is wider and the fourchette appears more
flattened. Over the next 6–12 weeks, the typical
morphology and dimensions of the vaginal tract
are reestablished.
Farage · Maibach
Menopause and Aging
The loss of follicular activity will lead to meno-
pause which is the permanent cessation of men-
struation. A constellation of symptoms emerges
during the perimenopause (the transition period
to menopause). The most notable is menstrual cy-
cle irregularity, reflecting an increase in the num-
ber of anovulatory cycles and cycles with a pro-
longed follicular phase. Some women experience
cramps, bloating or breast tenderness; symptoms
of estrogen depletion, such as vasomotor symp-
toms (‘hot flashes’), migraine and vaginal dryness
[45, 46], may ensue. The perimenopause typical-
ly commences after the age of 45 and lasts about
4 years. Menstruation ceases at a median age of
50 years in Western industrialized societies [47].
Menopause is considered established 1 year after
the final menstrual period [48].
The most apparent changes are the graying of
the pubic hair and becoming sparse, the loss of
subcutaneous fat in the labia majora and the labia
minora, vestibule, and vaginal mucosa atrophy
[16, 49]. At the cytological level, estrogen-induced
parakeratosis of the vulvar stratum corneum is
highest in the third decade of life, but rarely seen
by the eighth decade [50].
Postmenopausal atrophic vulvovaginitis is a
virtually universal condition [46, 51]. Vaginal se-
cretions decrease, reducing lubrication and in-
creasing coital discomfort [52]. Thinned tissue is
more easily irritated and may be more susceptible
to infection [53]. The vaginal pH rises, and the
prevalence of colonization by enteric organisms
associated with urinary tract infections increas-
es [54, 55]. Besides these physiologically induced
changes, certain vulvar dermatoses, such as lichen
sclerosus, are most prevalent in peri- and post-
menopausal women [46, 52, 56].
Vulvar skin differs from exposed skin in the
characteristics of skin hydration, friction, perme-
ability and visually discernible irritation (reviewed
in Oriba et al. [57] and Farage et al. [58]). It is
commonly assumed that aged skin is intrinsically
Morphology and Physiological Changes of Genital Skin and Mucosa
less hydrated, less elastic, more permeable and
more susceptible to irritation. However, assess-
ments of the vulvar skin of pre- and postmeno-
pausal women, using bioengineering techniques,
did not reveal large age-related changes in these
characteristics (table 2).
For example, the skin of the labia majora is
more hydrated than forearm skin as measured
by transepidermal water loss [62], and its coef-
ficient of friction is higher [59]. Although small
age-related changes in these parameters were
measured on the forearm of pre- and postmeno-
pausal women, the impact of the menopause on
the water barrier function and friction coefficient
of vulvar skin was negligible [59].
Vulvar skin is more permeable to hydrocorti-
sone than forearm skin, but comparable testos-
terone penetration rates have been measured at
both sites. In postmenopausal women, skin per-
meability to hydrocortisone drops on the forearm
but not on the vulva, and no age-related differ-
ences in testosterone penetration were found at
either site [60].
Exposed forearm skin was more susceptible
than vulvar skin to the model irritant, aqueous
sodium lauryl sulfate (1% w/v). This agent caused
more intense erythema on the forearms of pre-
menopausal women, but no visually discernible
response on the vulva in either pre- or postmeno-
pausal women [61].
Although large age-related differences in vul-
var skin permeability and intrinsic susceptibility
to irritants have not been demonstrated, dermati-
tis of the vulva, perineum and buttocks is never-
theless a significant problem in older people with
incontinence [63]. Studies of incontinence derma-
titis in infants have elucidated a multifactorial eti-
ology. In brief, exposure to urinary moisture un-
der occlusion makes the skin more susceptible to
friction damage; urinary ammonia elevates the lo-
cal pH, which alters skin barrier function [46, 53,
64–66] and activates fecal enzymes; these enzymes
further compromise skin integrity and increase
skin susceptibility to microbial infection [67–71].
15
Table 2. Skin physiological parameters in pre- and postmenopausal women (reproduced from Farage et al. [1] and
Farage and Maibach [2])

Parameter Body site Age groupa Measured valueb Significance Reference

Water barrier function forearm premenopausal 3.7 ± 0.4 p < 0.05 59

(TEWL, g/m2/h)
postmenopausal 2.6 ± 0.3

vulva premenopausal 14.8 ± 1.5 n.s. 59

postmenopausal 13.5 ± 1.8

Skin hydration forearm premenopausal 93.3 ± 2.3 n.s. 59

(capacitance, AU)
postmenopausal 91.9 ± 2.8

vulva premenopausal 116.8 ± 4.1 n.s. 59

postmenopausal 118.0 ± 8.2

Friction coefficient μ forearm premenopausal 0.49 ± 0.02 p < 0.05 59

postmenopausal 0.45 ± 0.01

vulva premenopausal 0.60 ± 0.04 n.s. 59

postmenopausal 0.60 ± 0.06

Hydrocortisone forearm premenopausal 2.8 ± 2.4 n.s. 60

penetration, % dose
absorbed postmenopausal 1.5 ± 1.1

vulva premenopausal 8.1 ± 4.1 p < 0.01 60

postmenopausal 4.4 ± 2.8

Testosterone forearm premenopausal 20.2 ± 8.1 n.s. 60

penetration, % dose
absorbed postmenopausal 14.7 ± 4.2

vulva premenopausal 26.7 ± 8.0 n.s. 60

postmenopausal 24.6 ± 5.5

Visual erythema forearm premenopausal 9 p = 0.03 61

scores (scored on day
2, i.e. 24 h after postmenopausal 5
exposure to 1% SLS) vulva premenopausal 0 n.s. 61

postmenopausal 0

aAge group sizes for water barrier function, skin hydration and friction parameters: premenopausal = 34 subjects,
postmenopausal = 10 subjects; for hydrocortisone and testosterone penetration: 9 subjects in each age group; for
visual erythema scores: 10 subjects per age group. TEWL = Transepidermal water loss, SLS = sodium lauryl sulfate;
bLevel of statistical significance of age group differences, n.s. = not significant.

16 Farage · Maibach
 Perineal dermatitis is particularly debilitating
to older people with incontinence because urine
and feces exert their effects against a background
of atrophied tissue, immobility, a potentially weak-
ened immune response, and often compromised
physical health and cognition [66, 72–74]. Several
factors exacerbate the deleterious effects of skin
wetness, occlusion and fecal enzyme action in el-
derly subjects [65]. Although the baseline skin
wetness level does not differ significantly in aged
skin, the excess hydration induced by occlusion is
significantly greater and dissipated more slowly in
older skin than in young [75]. Although the coef-
ficient of vulvar skin friction is unchanged in old-
er women, reduced mobility subjects atrophied
genital tissue to higher shear forces than those en-
countered by infants. Moreover, atrophied genital
tissue may be more susceptible to pH changes and
enzymatic action, while immune function and tis-
sue regeneration capacity may also be compro-
mised [51, 52]. Lastly, elderly individuals may not
receive the same degree of attentiveness as infants,
and those with impaired cognition may be unable
to alert caregivers to incontinent episodes. These
factors underscore the need for vigilant care and
proper hygiene to help maintain healthy urogeni-
tal skin in older women with incontinence.
In summary, the vulva and vagina undergo
characteristic age-related changes over a lifetime.
At birth, these tissues exhibit the effects of resid-
ual maternal estrogens. During puberty, the vulva
and vagina mature under the influence of adrenal
and gonadal steroid hormones. During the repro-
ductive years, the vagina responds to ovarian ste-
roid hormone cycling, and both tissues adapt to
the needs of pregnancy and delivery. Following
menopause, the vulva and vagina atrophy. A rise
in the prevalence of incontinence among older
women increases the risk of vulvar and perineal
dermatitis. Vigilant care and proper hygiene in el-
derly people, especially those with incontinence,
are needed to avoid dermatitis and skin deterio-
ration which may be debilitating at this stage of
life.

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Miranda A. Farage, PhD
Procter and Gamble Company, Feminine Care Innovation Center
6110 Center Hill Road, Box 136
Cincinnati, OH 45224 (USA)
Tel. +1 513 634 5594, Fax +1 866 622 0465, E-Mail farage.m@pg.com
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