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Contents lists available at ScienceDirect

Tissue and Cell

journal homepage: www.elsevier.com/locate/tice

Seasonal morphophysiological variations in the prostatic complex of

the Tarabul’s gerbil (Gerbillus tarabuli)
Arezki Kheddache a,b,∗∗ , Elara N’tima Moudilou c , Yamina Zatra a , Naouel Aknoun-Sail a ,
Zaina Amirat a , Jean-Marie Exbrayat c,∗ , Farida Khammar c
a
Laboratoire de Recherche sur les Zones Arides, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene. BP 32
El-Alia, 16111 Alger, Algérie
b
Université Mammoud Mammeri, Faculté des Sciences Biologiques et des Sciences Agronomiques, Département de Biologie, 15000 Tizi-Ouzou, Algérie
c
Université de Lyon, UMRS 449, Biologie Générale - Reproduction et Développement Comparé, Université Catholique de Lyon, EPHE/PSL, 10 place des
Archives, 69288 Lyon Cedex 02, France

a r t i c l e i n f o a b s t r a c t

Article history: Gerbillus tarabuli is a nocturnal Saharan rodent which has an annual reproductive cycle characterized by
Received 11 December 2015 the reproductive activity in spring and a long phase of sexual quiescence in other seasons. We describe
Received in revised form 8 June 2016 the morphology and hormonal regulation of the prostatic complex of this rodent in the two periods, based
Accepted 16 January 2017
on anatomical, histological, morphometric, and immunohistochemical analyses. The organisation of this
Available online xxx
prostatic complex is similar to that reported for Meriones unguiculatus, but different from the prostate
of Psammomys obesus, the rat, and the mouse. In addition to the anterior lobes, ventral lobes, and dorsal
Keywords:
lobes, the prostatic complex of Gerbillus tarabuli, also includes dorsolateral lobe. Each lobe is composed of
Saharan rodent
Gerbillus tarabuli
a fibro-muscular stroma surrounding a glandular epithelium. Dorsolateral lobes are easily distinguishable
Prostate by their big volume. The prostate grows and regresses cyclically throughout the year. During the resting
Morphology season, ventral lobes and anterior lobes showed atrophy, with a significant decrease in both epithelial
Regulation height and supranuclear area size, and a strong thickening of the fibro-muscular compartment. In dorsal
Seasonality lobes, the epithelial and stromal compartments atrophied and regenerated simultaneously, whereas in
dorsolateral lobe the thickness of the epithelium, the supranuclear zone and the stroma increased during
resting period. Furthermore, seasonal variations were observed in the distribution and expression of both
androgen receptors, and estrogens receptors. Expression patterns of all receptors were lobe-specific. In
conclusion, both androgens and estrogens are involved in the homeostasis and regulation of the prostate
in Gerbillus tarabuli. Dorsolateral lobe seems to be controlled by a different mechanism than other lobes.
© 2017 Elsevier Ltd. All rights reserved.

1. Introduction (Marker et al., 2003). In rodents, the prostate is composed of four

The prostate is a mammalian male accessory sex gland con-
tributing to the composition of sperm and ensuring the survival,
mobility, and viability of spermatozoa in both male and female
reproductive tract. Its anatomy varies according to the species
Abbreviations: ALs, anterior lobes; VLs, ventral lobes; DLs, dorsal lobes; DLLs,
dorsolateral lobe; AR, androgen receptors; ER!, estrogens receptors alpha; ER",
estrogens receptors beta.
∗ Corresponding author.
∗∗ Corresponding author at: Laboratoire de Recherche sur les Zones Arides, Faculté
des Sciences Biologiques ; Université Sciences et Technologie Houari Boumediene.
BP 32 El-Alia, 16111 Alger, DZ-Algérie.
E-mail addresses: aa ke@yahoo.fr (A. Kheddache),
jmexbrayat@univ-catholyon.fr (J.-M. Exbrayat).
pairs of lobes: ventral (VLs), lateral (LLs), dorsal(DLs), and ante-
rior lobes (ALs), or coagulating glands, located on the concave face
of the seminal vesicles (Jesik et al., 1982; Lin and Bissell, 1993;
Marker et al., 2003). Prostatic lobes comprise glandular epithe-
lium embedded in fibromuscular stroma (Hayward et al., 1996). The
development and function of prostate are regulated by an interac-
tion of androgens and estrogens.
Androgens and more particularly testosterone is necessary to
the prenatal and postnatal development of the male accessory
sex glands (Thomson, 2001). Biological effects of androgens are
mediated by their binding to receptors. The activation of androgen
receptors results in interactions with androgen response elements
(ARE) located in the regulatory regions of androgen-responsive
genes (Prins et al., 1991). Androgens stimulate prostate growth
and prevent cell apoptosis (Banerjee et al., 1995; Jang et al.,

http://dx.doi.org/10.1016/j.tice.2017.01.004
0040-8166/© 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
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2013). After castration, the epithelium regresses but the remaining
prostatic epithelial cells remain androgen-sensitive. Testosterone
replacement therapy results in the regeneration of the prostatic
epithelium, with the normal cell number and function being
restored. Androgen receptors are expressed and active in both
epithelial and stromal compartments. Stromal-epithelial interac-
tions were shown to be essential for the development of glandular
epithelium and they are also known to play a key role in the devel-
opment of some prostate diseases, such as prostate hypertrophy
and prostate cancer (Cunha et al., 2004).
It is well known that also estrogens are implicated in the
normal development and function of the prostate as well as in
the aetiology of prevalent prostatic diseases (Prins and Korach,
2008; Lazari et al., 2009). The effects of these hormones are medi-
ated primarily through the binding to the two major estrogens
receptors (ER) subtypes, ER! and ER" that are thought to be
ligand-activated transcription factors (Aranda and Pascual, 2001).
The effects of estrogens binding to these two ERs appear to
be antagonistic. The activation of ER! has been reported to be
responsible for aberrant cell proliferation, inflammation, and the
development of pre-malignant prostate lesions, whereas ER" acti-
vation has anti-proliferative, anti-inflammatory, and potentially
anti-carcinogenic effects in the prostate (Ellem and Risbridger,
2009). In rodents, neonatal exposure to high doses of estrogens
permanently imprints the growth and function of the prostate, pre-
disposing it to hyperplasia and severe dysplasia analogous to the
prostatic intraepithelial neoplasia related with aging (Prins et al.,
2001; Bianco et al., 2002).
Some comparative anatomic studies (macroscopic and micro-
scopic) of the prostate in rats, mice, and humans were reported
(Huss et al., 2001; Roy-Burman et al., 2004). Many studies have
been performed on the morphology of prostate of rodents belong-
ing to the Gerbilinae subfamily, like Praomys natalensis (Gross and
Didio, 1987), Psammomys obesus (Sprando et al., 1999), and Meri-
ones unguiculatus (Williams, 1974). Among these species, only the
Mongolian gerbil, Meriones unguiculatus, was suggested to be a
good model to study the prostate morphophysiology under differ-
ent experimental conditions (Cordeiro et al., 2008).
Seasonally breeding animals might be also useful for studying
androgen regulation of the male reproductive organs (Tähkä et al.,
1997). Many of Saharan rodents fall within this category. However,
little is known about their physiology and the hormonal regulation
of the accessory sex glands, particularly the prostate. In this study,
we focused on nocturnal Gerbillus tarabuli, a seasonal breeder with
the maximum sexual activity in spring (from January till the end
of May). In males, the seasonality of the reproduction is associated
with cyclic changes in the size and weight of the testes and the
seminal vesicles. The endocrine functions of the testes are at their
minimum in autumn and at their maximum in the beginning of
spring (Khammar and Brudieux, 1987).
The purposes of our study were: (1) to describe the anatomi-
cal, histological, and morphometric changes occurring during the
breeding and resting season, and (2) to investigate the expression
and possible seasonal variations in the expression and cellular dis-
tribution of ARs, ERs! and ERs" in the prostate of Gerbillus tarabuli.
2. Materials and methods
2.1. Animals
Ten adult male Tarabul’s gerbils (Gerbillus tarabuli) were cap-
tured in the Beni Abbes area (wilaya of Bechar, 30" 7" N, 2◦ 10 W) in
the Algerian Sahara in the middle of the breeding (n = 5) or resting
period (n = 5). All animals were caught in live traps, in the field near
the oasis. They were subsequently weighed, placed in cages and fed
Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
with barley. After 24–48 h, all animals were euthanized by cervi-
cal dislocation and dissected. The adults were defined as having a
body weight more than 32.8 g, as suggested by Granjon et al. (1999),
the location and morphology of testes characteristics of adults and
the presence of spermatozoa in testes revealed by means of light
microscopy.
2.2. Macroscopic analysis and tissue preparation
The prostatic lobes were separated, weighed, and fixed by a
48-h immersion in 10% neutral buffered formalin. Then, the sam-
ples were dehydrated with a graded ethanol series (70–95%–100%),
cleared in butanol, embedded in paraffin, and cut into sections of
5.0 #m for histological, morphometric, and immunohistochemical
analyses.
2.3. Histological and morphometric analysis
The sections were stained with haematoxylin-eosin-saffron
(HES) as described by Exbrayat (2013). To measure the epithelial
and supranuclear zone heights and stroma thickness, 50 random
fields from each prostatic lobe were imaged for each animal at a
magnification of 400, and measurements were performed in each
field, totalling 250 measurements for each group (breeding and
resting period). Digital images were obtained using a Nikon Eclipse
E400 microscope with a D.S-5 Mc camera and analysed with the
Nis-Elements BR 3.10
2.4. Immunohistochemistry
The expression and cell distribution of ARs, ER! and ER" were
visualized using immunohistochemistry. For that, sections were
dewaxed in cyclohexane, hydrated in an ethanol series of decreas-
ing concentrations (100% to 70%), and rinsed with tap water.
Antigen receptors were retrieved by boiling in 10 mM citrate buffer
(Vector Laboratories, pH 6.0) in a pressure cooker. Sections were
then incubated for 30 min in 0.3% hydrogen peroxide (Fisher Sci-
entific) in PBS buffer in order to quench endogenous peroxidase
activity, and washed twice with PBS. Non-specific binding sites
were blocked by a one-hour incubation with horse normal serum
at room temperature. The sections were then incubated (1 h, room
temperature) with the following primary antibodies: the ER! rab-
bit polyclonal IgG antibody (sc 7207, Santa Cruz Biotechnology;
diluted 1/200), the ER" polyclonal IgG antibody (sc 8974, Santa
Cruz Biotechnology; diluted 1/50), and the AR antibody (ab 74272,
Abcam plc; diluted 1/400). Negative control sections were incu-
bated with PBS instead of the primary antibody. Afterwards, all
sections were washed in PBS, and incubated for one hour with a
biotinylated secondary antibody (Vectastain Elite ABC kit-Vector
Laboratory). Following a 30-min incubation with an avidin-biotin-
peroxidase complex, the immunoreactions were labelled using
DAB chromogen (3, 3 diaminobenzidine, kit for peroxidase; Roche
Diagnostics; 1-min incubation). Haematoxylin QS (Vector Labora-
tories) was used to counterstain the sections. The percentage of
immunoreactive cells in prostatic lobes in each image was deter-
mined. The number of immunoreactive cells (Ni) and the number
of nuclei in unstained cells (Nu) were counted (Ni/(Ni + Nu) × 100).
The immunostaining results were evaluated using a Nikon Eclipse
E400 microscope and categorised as weakly positive (+), moder-
ately positive (++) or strongly positive (+++).
2.5. Statistical analysis
The body weight, organ weight, and morphometric measure-
ments were analysed using the Statistica software version 5.0, and
expressed as means with standard error of the mean (SEM) for each
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of the periods (breeding or resting). The statistical significance of

Breeding period
the difference between the two groups was determined using the

21.92 ± 1.14***
14.31 ± 0.32***
Student’s t-test. P-values ≤0.05 were considered as indicative of a

5.15 ± 0.21
statistical significance.

3. Results

DorsolateraL Lobe
3.1. Anatomy of prostatic complex

Resting period

32.73 ± 2.15
16.46 ± 0.33
5.72 ± 0.21
We found that the prostatic complex of Gerbillus tarabuli is
divided into four pairs of lobes. VLs, DLLs, and DLs surround the
prostatic urethra and ALs are located on the concave face of the
seminal vesicles. These symmetrical lobes encompass the urethra
at the base of the urinary bladder. DLLs can be easily distinguished

Breeding period

29.98 ± 1.61***
from the other lobes by their big volume and a butterfly-like shape.

5.87 ± 0.24***
12.99 ± 0.3**
VLs are located below the bladder neck, forming a compact oval
structure surrounded by adipose tissue. DLs are located between

Seasonal variations in the morphometric parameters of the prostatic lobes of the Tarabul’s gerbil (Gerbillus tarabuli) between the resting (n = 5) and breeding period (n = 5).
the bladder, seminal vesicles, and ALs occupying a central position
between the other lobes. Deferent ducts are inserted in this region
(Fig. 1).
The gerbil body weight was not significantly different between

Resting period

11.86 ± 0.25

21.96 ± 1.09
Dorsal Lobe
the breeding and the resting period (Fig. 2A). The prostatic complex

4.52 ± 0.15
underwent development in spring and atrophied in other seasons.
Between the two periods, the weight of prostatic lobes and semi-
nal vesicles reduced simultaneously with the testis regression. The
weight of the testes decreased significantly by an average 52.63%
and those of seminal vesicles by 118.25%. Prostatic lobes also sig-

Breeding period

23.69 ± 0.29***
nificantly decreased: by 211.45% in the ALs, 208.35% in DLs, and

7.43 ± 0.22***
15.97 ± 0.43*
121.04% in VLs. The DLLs weight reduced by 74.44% but this result
was not statistically significant (P-value >0.05; Fig. 2B).

3.2. Histological and morphometric analysis

Resting period
The prostate lobes were constituted of a secretory epithelial
Ventral Lobe

14.71 ± 0.41

39.56 ± 0.96
5.52 ± 0.34
tissue forming tubular units, and of fibromuscular stroma. The stro-
mal compartment consisted of a subepithelial region and a layer
of smooth muscle cells surrounding the tubules. Some seasonal
changes in the size of epithelial cells, supranuclear area, and the
stroma were observed throughout the year (Table 1). During the
breeding period, the lumen was larger with much more secretions
Breeding period

12.4 ± 0.29***
6.20 ± 0.21***

than in the resting period (Fig. 3 and 4).

45.47 ± 1.77

3.2.1. Anterior lobes

In spring, ALs were composed of very large tubules with highly
folded mucosa and a thick layer of smooth muscle cells. Epithelial
cells were cubic or low columnar with elliptical centrally located
Restingperiod
Anterior lobe

nuclei. This epithelium was surrounded by connective tissue and

49.35 ± 2.19
10.88 ± 0.34

Values are presented as means ± standard error of the mean (SEM).

3,65 ± 0.1

bordered a large lumen (Fig. 3B and D). During the resting season,
the wall muscular fibres were more developed, with increase in
the thickness of stroma (resting period: 49.35 #m ± 2.19, breeding
period: 45.47 #m ± 1.77; Table 1), the mucosa was unfolded into
a narrowed luminal area, and the epithelial cells where shorter
Mean height of the secretory epithelium (#m)

(resting period: 10.88 #m ± 0.34, breeding period: 12.4 #m ± 0.29;

Mean height of the supranuclear area (#m)

P-value <0.001) with a significant decrease in the size of the

supranuclear area (resting period: 3.65 #m ± 0.1, breeding period:
Mean thickness of the stroma (#m)

6.20 #m ± 0.21; P-value <0.001; Fig. 3A and C).

3.2.2. Ventral lobes

A histological analysis of VLs during the breeding season
revealed a simple, cylindrical epithelium with basally located
nuclei covering a wide lumen. The stroma was scarce, with few
P-value <0.001.
P-value ≤ 0.05.
P-value <0.01.

smooth muscle cells and connective tissue (Fig. 3F and H). During
the resting season, some changes were observed in the differ-
ent tissue compartments: a significant reduction in the volume of
Period
Table 1

the epithelium (resting period: 14.71 #m ±0.41, breeding period:

*

**

***

15.97 #m ± 0.43; P-value < 0.05; Table 1) and the supranuclear area

Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
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Fig. 1. Accessory sex glands (prostatic complex and seminal vesicles) in adult Gerbillus tarabuli. Ventral (A) and dorsal (B) views of the prostatic lobes. AL: anterior lobe, DL:
dorsal lobe, DLL: dorsolateral lobe VL: ventral lobe, of the prostate and VS: seminal vesicles, as well as the UB: urinary bladder, U: urethra, and a DD: deferent duct.

Fig. 2. Seasonal variations of the weight of body (A), testes, and accessory sex glands (B) in Gerbillus tarabuli. (RT) Right testes, (VS) seminal vesicles, (AL) Anterior lobe,
(VL) ventral lobe, (DL) dorsal lobe, (DLL) dorsolateral lobe. Values are presented as means ± standard error of the mean (SEM); n = 5 for each period.* P-value ≤ 0.05;**
P-value < 0.01;*** P-value < 0.001.

(resting period: 5.52 #m ± 0.34, breeding period: 7.43 ± 0.22 #m ±;
P-value <0.001), with a decrease in the width of the lumen and an
increased volume of the adjacent stroma (resting period: 39.56 #m
±0.96, breeding period: 23.69 #m ± 0.29; P-value <0.001; Fig. 3E
and G).
3.2.3. Dorsal lobes
The DLs morphology was similar to that of VLs, with tubule-
acinar units composed of cubic or columnar epithelial cells with
basally located oval nuclei, surrounded by fibromuscular stroma.
However, the secretory epithelium and the stromal organisa-
tion were different. Following the staining, the secretions in the
dorsal lobes were strongly basophilic with a vesiculous aspect
(Fig. 4B and D). Furthermore, during the resting season, these lobes
showed atrophy, with clear regression of the glandular epithelium,
reflected by a reduction of the acinar lumen devoid of secretion. The
height of the epithelium and of the supranuclear area decreased
significantly (resting period: 11.86 #m ± 0.25, breeding period:
12.99 #m ± 0.3, P-value <0.01 and resting period: 4.52 #m ± 0.15,
breeding period: 5.87 #m ± 0.24, P-value < 0.001, respectively;
Table 1). The adjacent stroma became significantly thinner (resting
period: 21.96 #m ± 1.09, breeding period: 29.98 #m ± 1.61 P-value
<0.001; Fig. 4 Aand C).
3.2.4. Dorsolateral lobes
Contrary to other lobes, DLLs did show neither histological dif-
ferences nor atrophy between the two periods. The tubule-acinar
units were surrounded by a dense stroma. The epithelium was com-
posed of a single layer of cubic or columnar secretion cells, with
round or oval centrally located nuclei. The epithelium invaginated
into the lumen filled with secretions during the two periods. DLLs
secretions were slightly acidophilic. Morphometric parameters
were also different than those obtained for other lobes: the height
of the epithelial cells and supranuclear area significantly decreased
during the breeding season (Resting: 16.46 #m ± 0.33; Breed-
ing: 14.31 #m ± 0.32; P-value <0.001, and Resting: 5.72 #m ± 0.21;
Breeding: 5.15 #m ± 0.21;respectively, Table 1). Interestingly, the
nuclei were located much more apically during the breeding period
than during the resting season, leaving a large infranuclear area. On
the contrary, the thickness of the fibromuscular stroma during the
breeding season significantly decreased (21.92 #m ± 1.14 as com-

Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
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Fig. 3. Histological variations of the anterior (A,B,C and D) and ventral (E,F,G and H) prostatic lobes of Gerbillus tarabuli during the resting (left) and breeding (right) period.
Haematoxylin-eosin-saffron (HES) staining) FS: fibromuscular stroma, CT: connective tissue, E: epithelium, SA: supranuclear area, L: lumen, S: secretions. Scale bar = 50 #m.

Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
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Fig. 4. Histological variations of the dorsal (A,B,C and D) and dorsolateral (E,F,G and H) prostatic lobes of Gerbillus tarabuli during the resting (left) and breeding (right) period.
Haematoxylin-eosin-saffron (HES) staining. FS: fibromuscular stroma, CT: connective tissue, E: epithelium, SA: supranuclear area, L: lumen, S: secretions. Scale bar = 50 #m.

Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
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pared to 32.73 #m ± 2.15 during the resting season, P-value <0.001;
Fig. 4E–H).
3.3. Expression of androgen and estrogens receptors
The expression and distribution of ARs, ERs! and ERs" during
the breeding and resting period were determined using immuno-
histochemistry (Fig. 5, Fig. 6 and Fig. 7, respectively). The results
werevalidated by a negative control. Prostatic lobes of all ani-
mals were positive for ARS and ERs, with a similar intensity of the
staining among different animals. The results are summarised in
Table 2 and 3, respectively.
3.3.1. Androgen receptors (AR)
In ALs, during the resting period, the ARs immunoreactivity was
observed in 59.37% of cells. The staining was intense in the stromal
cells and moderate in the epithelium. During the breeding period,
61% of cells were labelled. A strong signal for ARs was localised in
the epithelial cells, whereas it was weak in the stroma (Table 2;
Fig. 5A and B).
In VLs, during the resting period, the ARs immunoreactivity was
detected in 42.55% of cells, with a moderately positive staining in
epithelial cells, and a weak signal in stromal cells. During the breed-
ing period, an intense immunoreactivity was observed in about
80% of cells in both epithelial and stromal compartments (Table 2,
Fig. 5C and D).
In DLs, during the resting period, 45.69% cells were immunopos-
itive for ARs. These lobes contained numerous epithelial cells with
an intense nuclear staining. In contrast, the cells of fibromus-
cular stroma were weakly positive. During the breeding period,
the ARs expressions were different: they effected 52.35% of cells
.The immunostaining increased in the stromal compartment and
decreased in secretory cells (Table 2; Fig. 5E and F).
In DLLs, the highest ARs immunoreactivity was observed dur-
ing the resting period, 51.97% of cells expressing ARs). Highly
and moderately immunopositive cells were observed in epithe-
lial and stromal compartments respectively. During the breeding
period, the ARs immunoreactivity decreased (44.92% of cells). The
immunostaining became moderately positive in epithelial cells and
weak in stromal cells (Table 2, Fig. 5G and H)
3.3.2. Estrogens receptor alpha (ER˛)
During the resting period, the ER! immunoreactivity was
intense in epithelial and moderate in stromal cells of the ALs, with
53.18% cells stained. During the breeding period, the percentage of
immunostained cells decreased to 47.95% to become moderate in
both histological compartments (Table 3, Fig. 6A and B).
In the VLs, the ER! immunoreactivity was moderate in the
epithelial cells and weak in stromal cells during the resting period,
with 36.69% of positive cells. During the breeding period, the per-
centage of the immunostained cells increased (53.92%) and it was
intense in the epithelium and moderate in the stroma (Table 3,
Fig. 6C and D).
DLs exhibited a moderate immunoreactivity for ER! in epithelial
and stromal cells during the resting period, with 51.62% of posi-
tive cells. During the breeding period, the ER! immunoreactivity
decreased (45.22% of cells) and immunostaining was weak in the
epithelial and moderate in stromal cells (Table 3, Fig. 6E–F).
During the resting period, 49.27% of cells were immunostained
for ER! in the DLLs with a moderate signal in both compartments.
Approximately 44.70% of cells were ER!-immunpositive during the
breeding period. As compared to the resting period, in the epithelial
compartment reactivitiy has not changed and that in the stromal
cells became weak (Table 3, Fig. 6G–H).
Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
7
3.3.3. Estrogens receptor beta (ERˇ)
In ALs, the ER" immunoreactivity was intense in the epithelial
and stromal cells during the resting period, with 57.78% of pos-
itive cells. During the breeding period, the immunostaining was
moderate in the epithelium and weak in the stroma. However, the
percentage of positives cells increased (72.5%) (Table 3, Fig. 7A–B).
During the resting period, the epithelial and stromal cells of VLs
were weakly immunoreactive for ER" with staining observed in
40.64% of cells. The immunostaining was intense in the epithelium
and moderate in the stroma with 63.63% of positive cells during the
breeding period (Table 3, Fig. 7C–D).
During the resting period, the ER" immunoreactivity was weak
in the epithelium and intense in the stromal cells of DLs with 56.42%
of positive cells. In contrast, the percentage of immunostained cells
increased in spring (64.26%) and became intense in both compart-
ments of these prostatic lobes (Table 3, Fig. 7E–F).
In the DLLs, the ER" immunoreactivity was intense in the epithe-
lium and moderate in the stromal cells. Unlike in the other prostatic
lobes, the number of positive cells was high (52.86%) during the
resting period. During the breeding period, the percentage of ER"
immunoreactivve cells decreased (47.75%) and the signal was mod-
erate in the epithelium and weak in the stromal cells (Table 3,
Fig. 7G–H).
4. Discussion
Numerous prostate studies have been carried out. Nevertheless,
studies referring to cyclic variations in the prostate of wild ani-
mals remain scarce. To our knowledge, this study is the first report
which describes the morphophysiology of the prostatic complex in
Gerbillus tarabuli, a Saharan rodent with a seasonal reproductive
cycle.
We found that the prostatic complex of Gerbillus tarabuli is
divided into four isolated pairs of lobes attached to the urethra:
VLs, DLs, DLLs, and ALs. Such an anatomical organisation was also
found in other nocturnal Saharan gerbils such as Meriones lybicus,
Meriones crassus, Gerbillus gerbillus and Gerbillus nanus (unpub-
lished data), and in the Mongolian gerbil (Meriones unguiculatus;
Rochel et al., 2007). We observed that in the Tarabul’s gerbil, the
DDLs can be easily distinguished from the other lobes by their
big volume, a butterfly-like shape and location. A similar obser-
vation was reported for Meriones unguiculatus (Rochel et al., 2007).
In the mouse (Sugimura et al., 1986a, 1986b), rat (Jesik et al., 1982;
Hayashi et al., 1991), and sand rat (Sprando et al., 1999), the DLs
were the least developed and the VLs constituted about one half
of the mass of the entire prostatic complex. The presence of iso-
lated lobes is common for most rodents studied to date, however a
different organisation was observed in diurnal Saharan gerbil Psam-
momys obesus (Sprando et al., 1999), and in the mouse and rat (Price,
1963). Therefore, this particular anatomic structure of the prostatic
complex could to be characteristic for the two genera Gerbillus and
Meriones, belonging to the Gerbillinae subfamily.
In Gerbillus tarabuli, a reduction of the weight of prostatic lobes
and seminal vesicles was simultaneous to the testis regression
occurring between the breeding and resting season. This result
is in accordance with those obtained by Khammar and Brudieux
(1987) and Boufermes et al. (2013) for seminal vesicles in sym-
patric species: Gerbillus gerbillus and Meriones lybicus. These studies
showed that serum testosterone levels and weight of both the
gonads and seminal vesicles increased in spring and decreased in
other seasons. Previous work on our species showed atrophy of the
seminal vesicles and other organs of the genital tract after castra-
tion occurring during the breeding season (Keddache, 2007). The
prostatic lobes of Gerbillus tarabuli did not show the same degree
of atrophy during the resting season, with the DLLs showing no
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Fig. 5. Immunolocalisation of AR in the prostatic lobes of Gerbillus tarabuli during the resting (left) and breeding (right) period. The sections were counterstained with haema-
toxylin. A–B: anterior lobe, C–D: ventral lobe, E–F: dorsal lobe, G–H: dorsolateral lobe. No immunostaining was observed in the negative control (insert). FS: fibromuscular
stroma, E: epithelium, L: lumen, S: secretions. Scale bar = 50 #m.

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Fig. 6. Immunolocalisation of ER! in the prostatic lobes of Gerbillus tarabuli during the resting (left) and breeding (right) period. The sections were counterstained with haema-
toxylin. A–B: anterior lobe, C–D: ventral lobe, E–F: dorsal lobe, G–H: dorsolateral lobe. No immunostaining was observed in the negative control (insert). FS: fibromuscular
stroma, E: epithelium, L: lumen, S: secretions. Scale bar = 50 #m.

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Fig. 7. Immunolocalisation of ER" in the prostatic lobes of Gerbillus tarabuli during the resting (left) and breeding (right) period. The sections were counterstained with haema-
toxylin. A–B: anterior lobe, C–D: ventral lobe, E–F: dorsal lobe, G–H: dorsolateral lobe. No immunostaining was observed in the negative control (insert). FS: fibromuscular
stroma, E: epithelium, L: lumen, S: secretions Scale. bar = 50 #m.

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Table 2
Immunolocalisation of androgen receptors (ARs) in the prostatic lobes of the Tarabul’s gerbil during the resting and breeding seasons.

Resting period Breeding period

Anterior lobe % Immunopositive cells 59.37% 61%

EP ++ +++
S +++ +

Ventral lobe % Immunopositive cells 42.55% 80%

EP ++ +++
S + +++

Dorsal Lobe % Immunopositive cells 45.69% 52.35%

EP +++ ++
S + +++

Dorsolaterl Lobe % Immunopositive cells 51.97% 44.92%

EP +++ ++
S ++ +

EP: label intensity in epithelial cells, S:label intensity in stroma. (+): weakly positive, (++): moderately positive, (++ + ): strongly positive staining.

Table 3
Variations of the immunostaining intensity for estrogen receptors (ER! and ER") in the prostatic lobes of the Tarabul’s gerbil during the resting and breeding period.

ER! ER"

Resting period Breeding period Resting period Breeding period

Anterior lobe % Immunopositive cells 53.18% 47.95% 57.78% 72.50%

EP +++ ++ +++ ++
S ++ ++ +++ +

Ventral lobe % Immunopositive cells 36.69% 53.92% 40.64% 63.63%

EP ++ +++ + +++
S + ++ + ++

Dorsal Lobe % Immunopositive cells 51.62% 45.22% 56.42% 64.26%

EP ++ + + +++
S ++ ++ +++ +++

Dorsolateral Lobe % Immunopositive cells 49.27% 44.70% 52.86% 47,75%

EP ++ ++ +++ ++
S ++ + ++ +

EP: staining intensity in epithelial cells, S: staining intensity in stroma. (+): weakly positive, (++): moderately positive, (+++): strongly positive staining.

significant regression. A similar heterogeneity was reported for
other rodent species. In Syrian hamster, Mesocricetus auratus, the
VLs showed a weak seasonal regression, whereas the DLs markedly
regressed when the days shortened (Buzzell, 1989). It is probable
that the differences in the extent of atrophy between the prostate
lobes we observed in the Tarabul’s gerbil were due to apoptosis
occurring at different levels in different lobes, as it was observed
in Rat (Banerjee et al., 1995; Woolveridge et al., 1998; Jang et al.,
2013). Variations in the weight of the prostatic complex indicate a
higher activity of the gland during the breeding period.
Our results show that the DLLs, VLs, and DLs present a common
histological organisation pattern: infolded mucosa, thin fibromus-
cular stroma, and the presence of several small lumina. However,
the ALs are the components differing the most from the other
lobes due to a larger thickness of the muscular layer, a highly
folded mucosa and some wide secretory cavities. These histolog-
ical characteristics resemble those of seminal vesicles. During the
breeding period, the microscopic anatomy of the prostatic com-
plex of Gerbillus tarabuli was similar to that documented for other
rodent species (Price, 1963; Buzzell, 1989; Sugimura et al., 1986a,
1986b; Hayashi et al., 1991; Sprando et al., 1999). It has been shown
that during the resting, the prostatic complex of Gerbillus tarabuli
underwent histological changes, and it is well documented that
the prostate involuted following androgen withdrawal. This invo-
lution includes decreasing the epithelium height, acinus shrinkage
and stromal remodelling (Huttunen et al., 1981; Holterhus et al.,
1993).Therefore; we conclude that the structure of the prostatic
lobes of Gerbillus tarabuli changes during the seasonal reproductive
cycle.
Morphometrical examination of the prostatic lobes of adult Ger-
billus tarabuli showed distinctive morphological features for each
lobe according to the season. The secretory epithelium and the
supranuclear zone significantly decreased in size during the rest-
ing period in the ALs, VLs and DLs, which explains the absence of
secretions, as was seen after castration in other rodents (Sugimura
et al., 1986b; Holterhus et al., 1993). In contrast, in the DLLS their
size increased during this period.
We found that the fibro-muscular compartment thickness of
prostatic lobes in the Tarabul’s gerbil varied significantly between
the two periods. In the ALs, VLs and DLLs, when the secretory
epithelium was the most active, the adjacent stroma was less thick
compared with the period at which the epithelium atrophied. Sim-
ilar seasonal histological variations were noted in seminal vesicles
of Meriones libycus (Belhocine et al., 2007) and accessory sex glands
of the bank vole, Clethrionomys glareolus (Tähkä et al., 1997). This
phenomenon was also observed after androgenic deprivation fol-
lowing castration in the rat, the Mongolian gerbil (Oliveira et al.,
2007), and in The Tarabul’s gerbil (Keddache, 2007). On the other
hand, the volume of the DLs stroma, epithelium and lumen signifi-
cantly increased during the breeding period and decreased during
sexual quiescence. The histological and quantitative data suggest
the existence of lobe-specific mechanisms for stroma remodelling.
Stromal-epithelial interactions appear to be essential for the devel-
opment of glandular epithelium and they are also known to play
a key role in the development of the prostate (Cunha et al., 2004).
Vilamaior et al. (2005) demonstrated that smooth muscle cells of
the rat ventral prostate converted from a contractile to a synthetic
phenotype after surgical castration. Belhocine et al. (2010) reported
that in Meriones libycus gelatinases implicated in the extracellu-

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lar matrix remodelling were abundant in the seminal vesicles and
ventral prostate during the resting period. It is highly probable
that these enzymes are at the origin of the fibro-muscular stroma
thickening in the Gerbillus tarabuli prostatic lobes.
Immunohistochemical analyses showed some variations in the
expression, distribution and immunostaining of ARs in the prostatic
lobes of Gerbillus tarabuli throughout its reproductive cycle. These
results indicate a differential regulation of the different lobes. Com-
parable results were reported in the rat (Prins and Woodham, 1995;
Banerjee et al., 2001; Yamashita, 2004) and mouse (Yamashita,
2004). Thus, the changes in the androgen peripheral blood con-
centrations triggered changes in the expression of the ARs. In
spring, the expression of ARs increased, inducing proliferation and
secretory activity of the epithelial cells. Comparable results were
reported for both mouse and rat by Takeda et al. (1991), and by
Maffini et al. (2002) in rats. We also observed seasonal variations in
the expression of the ARs in the stromal compartment, suggesting
that this compartment is implicated in maintaining differentiation
and homeostasis of the prostate. Stromal cells produce mitogens
stimulating proliferation of prostate epithelial cells (Cunha et al.,
2004; Kato et al., 2013). Thus, these androgen–mediated paracrine
and autocrine effects maintain homeostasis in the adult prostate
(Kasai et al., 1996; Nieto et al., 2014). The stromal-epithelial
interactions within the prostate are often dependent on the ARs.
Androgens can have either a stimulatory or anti-proliferative effect,
depending on the microenvironment and the hormone levels (Nieto
et al., 2014). Cordeiro et al. (2008) analysed the AR expression in
the ventral prostatic lobes of the Mongolian gerbil during different
phases of postnatal development and following androgen block-
age. They showed that both the regulation and distribution of the
ARs are complex mechanisms that are likely to be regulated pre-
natally by androgens or by other factors which still unknown. Our
results clearly show that the morphology and function of the pro-
static complex in Gerbillus tarabuli is under permanent control of
androgens.
The prostatic lobes of the Tarabul’s gerbil are also clearly under
control of estrogens. In our study, the distribution of the ERs
expression was lobe-specific, with both estrogen receptors (ER!
and ER") expressed in the glandular epithelium and stroma of
the prostatic lobes. The expression differed with the atrophy and
regeneration of these lobes. Therefore, we conclude that estrogens
are involved in the homeostasis and physiology of the prostate
gland. Lobe-specific responses to estrogens have been also reported
in the mouse (Risbridger et al., 2001; Yamashita, 2004) and rat
(Yamashita, 2004). The ER! expression was usually localised in
the stromal cells of adult prostate in men (Tsurusaki et al., 2003),
dogs (Gallardo et al., 2007), monkeys, rats, and mice (Ellem and
Risbridger, 2009). The ER"s were mainly expressed in the epithe-
lium of rats, mice and men (Ellem and Risbridger, 2009; Lazari
et al., 2009; Adebayo et al., 2014). In Gerbillus tarabuli, both recep-
tor types were found in the epithelium and the stroma with some
variations of the expression between the two seasons. Estrogens
produced by aromatization of the testosterone were shown to act
on the proliferation of the prostatic lobes upon binding to ER!.
On the contrary, their binding to ER" had anti-proliferative effects
(Ellem and Risbridger, 2009). According to Asano et al. (2003),
testosterone regulates the expression of estrogens receptors. ER"s
were expressed when testosterone concentration increased. This
explains its strong expression observed in the nuclei of the epithe-
lial cells of the prostatic lobes during the breeding period. Recently,
Cândido et al. (2012) showed that the androgen/estrogens ratio
leads to deferential ERs immunoreactivity in the epithelial and stro-
mal compartments. Our results are in line with those of Beguelini
et al. (2015) who reported that the expression of ARs and ERs! in
the prostatic complex of a bat Myotis nigricans during the resting
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gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
period was essential for the reactivation of the gland, allowing the
increase of testosterone levels.
Interestingly, the dorsolateral lobes (DLLs) of Gerbillus tarabuli
did not react to the change of periods like the other lobes. This sug-
gests that it may be regulated by some other hormone, for example
prolactin whose implication in the regulation of the male reproduc-
tive tract was suggested by previous studies (Costello and Franklin,
1994; Laszczyñska, 2002).
In addition to the ALs, VLs and DLs, the prostatic complex of
Gerbillus tarabuli also possesses a pair of DLLs. The seasonal mor-
phophysiological variations observed in the prostatic complex are
in accordance with the results previously obtained for the gonads
and seminal vesicles of all the studied Saharans rodents with a
photoperiod-dependent reproduction cycle. Moreover, the results
of this study show different patterns of the ARs and ERs expression
in the different prostatic lobes and according to the season of the
reproductive cycle, suggesting the direct effect of these hormones
on the prostate in Saharan rodents.
Acknowledgments
The authors thank all the personnel of the Beni Abbes Station
in the Algerian Sahara for catching the gerbils. They also thank C
Bouchot, N.Djouada, and S. Amroun for technical assistance and M.
Raquet for technical advice. They gratefully acknowledge a financial
support of the Algerian Ministry of Higher Education and Scien-
tific Research, the Agence Universitaire de la Francophonie (AUF)
and from the Algerian–French collaborative Project Hubert-Curien
Tassili 09 MDU 756.
References
Adebayo, A.O., Akinloye, A.K., Olukole, S.G., Ihunwo, A.O., Oke, B.O., 2014.
Anatomical and immunohistochemical characteristics of the prostate gland in
the greater cane rat (Thryonomys swinderianus). Anat. Histol. Embryol 44 (2),
138–1345.
Aranda, A., Pascual, A., 2001. Nuclear hormone receptors and gene expression.
Physiol. Rev. 81 (3), 1269–1304.
Asano, K., Maruyama, S., Usui, T., Fujimoto, N., 2003. Regulation of estrogen
receptor alpha and beta expression by testosterone in the rat prostate gland.
Endocr. J. 50 (3), 281–287.
Banerjee, P.P., Banerjee, S., Tilly, K.I., Tilly, J.L., Brown, T.R., Zirkin, B.R., 1995. Lobe
specific apoptotic cell death in rat prostate after androgen ablation by
castration. Endocrinology 136 (10), 4368–4376.
Banerjee, P.P., Banerjee, S., Brown, T.R., 2001. Increased androgen receptor
expression correlates with development of age-dependent, lobe-specific
spontaneous hyperplasia of the brown Norway rat prostate. Endocrinology 142
(9), 4066–4075.
Beguelini, M.R., Goes, R.M., Rahal, P., Morielle-Versute, E., Taboga, S.R., 2015.
Impact of the processes of testicular regression and recrudescence in the
prostatic complex of the Bat, Myotis nigricans (Chiroptera: vespertilionidae). J.
Morphol. 20 (10), 1002.
Belhocine, M., Gernigon-Spychalowicz, T., Robert, A.M., Schoevaert, D.,
Bennazzoug, Y., Exbrayat, J.M., 2007. Ecophysiological responses of seminal
vesicles of Libyan jird (Meriones libycus) to the Saharan conditions:
histological, morphometrical and immunohistochimical analysis. Histol.
Histopathol. 22 (3), 603–615.
Belhocine, M., Gernigon-Spychalowicz, T., Jacob, M.P., Benazzoug, Y., Exbrayat, J.M.,
2010. Immunoexpression of gelatinase (MMP-2 and MMP-9) in the seminal
vesicles and ventral prostate of Libyan jird (Meriones libycus) during the
seasonal cycle of reproduction. Histol. Histopathol. 25 (5), 619–636.
Bianco, J.J., Handelsman, D.J., Pedersen, J.S., Risbridger, G.P., 2002. Direct response
of the murine prostate gland and seminal vesicles to estradiol. Endocrinology
143 (12), 4922–4933.
Boufermes, R., Amirat, Z., Khammar, F., 2013. Etude comparative des variations
saisonnières des activités testiculaire et thyroïdienne chez deux espèces de
rongeurs déserticoles: la gerbille (Gerbillus gerbillus) et le rat des sables
(psammomys obesus). Sci. Technol. C 37, 16–21.
Buzzell, G.R., 1989. Architecture of the dorsal and ventral lobes of the prostate of
the Syrian hamster Mesocricetus auratus, after regrowth from short
day-induced regression. J. Reprod. Fertil. 85 (2), 563–568.
Cândido, E.M., Fávaro, W.J., Montico, F., Hetzl, A.C., Cagnon, V.H.A., 2012.
Senescence and steroid hormone receptor reactivities in accessory sex glands
of elderly rats (Sprague-Dawley) following exogenous hormonal therapy.
Tissue Cell 44 (4), 227–237.
G Model
YTICE-1070; No. of Pages 13 ARTICLE IN PRESS
A. Kheddache et al. / Tissue and Cell xxx (2017) xxx–xxx
Cordeiro, R.S., Scarano, W.R., Campos, S.G., Santos, F.C., Vilamaior, P.S., Góes, R.M.,
Taboga, S.R., 2008. Androgen receptor in the Mongolian gerbil ventral prostate:
evaluation during different phases of postnatal development and following
androgen blockage. Micron 39 (8), 1312–1324.
Costello, L.C., Franklin, R.B., 1994. Effect of prolactin on the prostate. Prostate 24
(3), 162–166.
Cunha, G.R., Ricke, W., Thomson, A., Marker, P.C., Risbridger, G., Hayward, S.W.,
Wang, Y.Z., Donjacour, A.A., Kurita, T., 2004. Hormonal, cellular, and molecular
regulation of normal and neoplastic prostatic development. J. Steroid Biochem.
Mol. Biol. 92 (4), 221–236.
Ellem, S.J., Risbridger, G.P., 2009. The dual, opposing roles of estrogen in the
prostate. Ann. N. Y. Acad. Sci. 1155, 174–186.
Exbrayat, J.M., 2013. Classical methods of visualization. In: Exbrayat, J.M. (Ed.),
Histological and Cytochemical Methods of Visualization. CRC Press, Taylor et
Francis Group, Boca Raton, London, New York, pp. 5–58.
Gallardo, F., Mogas, T., Baró, T., Rabanal, R., Morote, J., Abal, M., Reventós, J.,
L.Ioreta, J., 2007. Expression of androgen, estrogens alpha and beta, and
progesterone receptors in the canine prostate: differences between normal,
inflamed, hyperplastic and neoplastic glands. J.Comp. Pathol. 136 (1), 1–8.
Granjon, L., Bonnet, A., Hamdine, W., Volobouev, V., 1999. Reevaluation of the
taxonomic status of North African gerbils usually referred to as Gerbillus
pyramidum (Gerbillinae, Rodentia): Chromosomal and biometrical data. Z.
Saugetierkunde 64, 298–307.
Gross, S.A., Didio, L.J., 1987. Comparative morphology of the prostate in adult male
and female Praomys (Mastomys) natalensis studied with electron microscopy. J.
Submicrosc. Cytol. 19 (1), 77–84.
Hayashi, N., Sugimura, Y., Kamamura, J., Doncajour, A.A., Cunha, G.R., Rubin, M.A.,
Humphrey, P.A., Sundberg, J.P., Rozengurt, N., Barrios, R., 1991. Morphological
and fuctional hetereogeneity in the rat prostatic gland. Biol. Reprod. 45 (2),
308–321.
Hayward, S.W., Baskin, L.S., Haughney, P.C., Foster, B.A., Cunha, A.R., Dahiya, R.,
Prins, G.S., Cunha, G.R., 1996. Stromal development in the ventral prostate,
anterior prostate and seminal vesicle of the rat. Acta Anat. 155 (2), 94–103.
Holterhus, P.M., Zhao, G.Q., Aumüller, G., 1993. Effects of androgen deprivation and
estrogen treatment on the structure and protein expression of the rat
coagulating gland. Anat. Rec. 235 (2), 223–232.
Huss, W.J., Maddison, L.A., Greenberg, N.M., 2001. Autochthonous mouse models
for prostate cancer: past, present and future. Semin. Cancer Biol 11 (3),
245–260.
Huttunen, E., Romppanen, T., Helminen, H.J., 1981. A histoquantitative study on
the effects of castration on the rat ventral prostate lobe. J. Anat. 132, 357–370.
Jang, H., Bae, W.J., Kim, S.J., Yuk, S.M., Han, D.S., Ha, U.S., Hwang, S.Y., Yoon, S.H.,
Wang, Z., Kim, S.W., 2013. The effect of anthocyanin on the prostate in an
andropause animal model: rapid prostatic cell death by apoptosis is partially
prevented by anthocyanin supplementation. World J. Mens Health 31 (3),
239–246.
Jesik, C.J., Holland, J.M., Lee, C., 1982. An anatomic and histologic study of the rat
prostate. Prostate 3 (1), 81–97.
Kasai, S., Sugimura, K., Matsumoto, K., Nishi, N., Kishimoto, T., Nakamura, T., 1996.
Hepatocyte growth actor is a paracrine regulator of rat prostate epithelial
growth. Biochem. Biophys. Res. Comm. 228, 646–652.
Kato, M., Ishii, K., Iwamoto, Y., Sasaki, T., Kanda, H., Yamada, Y., Arima, K., Shiraishi,
T., Sugimura, Y., 2013. Activation of FGF2-FGFR signaling in the castrated
mouse prostate stimulates the proliferation of basal epithelial cells. Biol.
Reprod 89, 1–10.
Keddache, A., 2007. Influence De La Castration Sur Les vésicules séminales De La
Gerbille (Gerbillus Tarabuli): étude Histologique Et électrophorèse Des
Protéines. Thèse De Magister. Alger, FSB, USTHB, 101p.
Khammar, F., Brudieux, R., 1987. Seasonal changes in testicular contents and
plasma concentrations of androgens in the desert gerbil (Gerbillus gerbillus). J.
Reprod. Fertil. 80 (2), 589–594.
Laszczyñska, M., 2002. Role of prolactin in male reproductive system. Post Biol.
Kom. 29, 45–59.
Lazari, M.F., Lucas, T.F., Yasuhara, F., Gomes, G.R., Siu, E.R., Royer, C., Fernandez,
S.A., Porto, C.S., 2009. Estrogen receptors and function in the male reproductive
system. Arq. Bras. Endocrinol. Metabol. 53 (8), 923–933.
Lin, C.Q., Bissell, M.J., 1993. Multi-faceted regulation of cell differentiation by
extracellular matrix. FASEB J. 7 (9), 737–743.
Please cite this article in press as: Kheddache, A., et al., Seasonal morphophysiological variations in the prostatic complex of the Tarabul’s
gerbil (Gerbillus tarabuli). Tissue Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.01.004
13
Maffini, M.V., Geck, P., Powell, C.E., Sonnenschein, C., Soto, A.M., 2002. Mechanism
of androgen action on cell proliferation: AS3 protein as a mediator of
proliferative arrest in the rat prostate. Endocrinology 143 (7), 2708–2714.
Marker, P.C., Donjacour, A.A., Dahiya, R., Cunha, G.R., 2003. Hormonal, cellular, and
molecular control of prostatic development. Dev. Biol. 253 (2), 165–174.
Nieto, C.M., Rider, L.C., Cramer, S.D., 2014. Influence of stromal epithelial
interactions on androgen action. Endocr. Relat. Cancer 21 (4), 147–160.
Oliveira, S.M., Leite Vilamaior, P.S., Corradi, L.S., Góes, R.M., Taboga, S.R., 2007.
Cellular and extracellular behavior in the gerbil (Meriones unguiculatus) ventral
prostate following different types of castration and the consequences of
testosterone replacement. Cell Biol. Int 31 (3), 235–245.
Price, D., 1963. Comparative aspects of development and structure in the prostate.
Nat. Cancer Inst. Monogr. 12, 1–27.
Prins, G.S., Korach, S., 2008. The role of estrogens and estrogen receptors in normal
prostate growth and disease. Steroids 73 (3), 233–244.
Prins, G.S., Woodham, C., 1995. Autologous regulation of androgen receptor
messenger ribonucleic acid in the separate lobes of the rat prostate gland. Biol.
Reprod. 53 (3), 609–619.
Prins, G.S., Birch, L., Greene, G.L., 1991. Androgen receptor localization in different
cell types of the adult rat prostate. Endocrinology 129 (6), 3187–3199.
Prins, G.S., Birch, L., Couse, J.F., Choi, I., Katzenellenbogen, B., Korach, K.S., 2001.
Estrogen imprinting of the developing prostate gland is mediated through
stromal estrogen receptor alpha: studies with alphaERKO and betaERKO mice.
Cancer Res. 61 (16), 6089–6097.
Risbridger, G.P., Wang, H., Frydenberg, M., Cunha, G., 2001. The metaplastic effects
of estrogen on mouse prostate epithelium: proliferation of cells with basal cell
phenotype. Endocrinology 142 (6), 2443–2450.
Rochel, S.S., Bruni-Cardoso, A., Taboga, S.R., Vilamaior, P.S.L., Goes, R.M., 2007. Lobe
identity in the Mongolian Gerbil prostatic complex: a new rodent model for
prostate study. Anat. Rec. 290 (10), 1233–1247.
Roy-Burman, P., Wu, H., Powell, W.C., Hagenkord, J., Cohen, M.B., 2004. Genetically
defined mouse models that mimic natural aspects of human prostate cancer
development. Endocr. Relat. Cancer 11 (2), 225–254.
Sprando, R.L., Collins, T.F., Black, T.N., Olejnik, N., Rorie, J.I., West, L.J., Bowers, J.D.,
Sass, N., Robl, M., 1999. Light microscopic observations on the reproductive
tract of the male sand rat, Psammomys obesus. Tissue Cell 31 (1), 99–115.
Sugimura, Y., Cunha, G.R., Donjacour, A.A., 1986a. Morphogenesis of ductal
networks in the mouse prostate. Biol. Reprod. 34 (5), 961–971.
Sugimura, Y., Cunha, G.R., Donjacour, A.A., 1986b. Morphological and histological
study of castration-induced degeneration and androgen-induced regeneration
in the mouse prostate. Biol. Reprod. 34 (5), 973–983.
Tähkä, K.M., Zhuang, Y.H., Tähkä, S., Tuohimaa, P., 1997. Photoperiod-induced
changes in androgen receptor expression in testes and accessory sex glands of
the bank vole, Clethrionomys glareolus. Biol. Reprod. 56 (4), 898–908.
Takeda, H., Nakamoto, T., Kokontis, J., Chodak, G.W., Chang, C., 1991.
Autoregulation of androgen receptor expression in rodent prostate:
immunohistochemical and in situ hybridization analysis. Biochem. Biophys.
Res. Comm 77 (1), 488–496.
Thomson, A.A., 2001. Role of androgens and fibroblast growth factors in prostatic
development. Reproduction 121 (2), 187–195.
Tsurusaki, T., Aoki, D., Kanetake, H., Inoue, M., Muramatsu, M., Hishikawa, Y., Koji,
T., 2003. Zone-dependent expression of estrogens receptors ! and " in human
benign prostatic hyperplasia. J. Clin. Endocrinol. Metab 88 (3), 1333–1340.
Vilamaior, P.S., Felisbino, S.L., Taboga, S.R., Carvalho, H.F., 2005. Modulation of
smooth muscle cell function: morphological evidence for a contractile to
synthetic transition in the rat ventral prostate after castration. Cell Biol. Int. 29,
809–816.
Williams, W.M., 1974. The Anatomy of the Mongolian Gerbil (Meriones
Unguiculatus). Tumblebrook Farm, inc. Université de Cornell, West Brookfield,
MA, pp. 107.
Woolveridge, I., Taylor, M.F., Wu, F.C., Morris, I.D., 1998. Apoptosis and related
genes in the rat ventral prostate following androgen ablation in response to
ethane dimethanesulfonate. Prostate 36 (1), 23–30 (15).
Yamashita, S., 2004. Localization of estrogen and androgen receptors in male
reproductive tissues of mice and rats. Anat Rec. A Discov. 279 (2), 768–778.