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REPRODUCTIVE AND DEVELOPMENTAL EFFECTS OF A
THYROTROPIC EXTRACT FROM POTENTILLA ALBA IN
MALE RATS
Komiljonova Oygul Olimjonovna
Fundamental tibbiyot kafedrasi
Osiyo Xalqaro Universiteti
Email: komiljonovaoygulolimjonovna@oxu.uz
https://doi.org/10.5281/zenodo.15523630
ARTICLE INFO
ABSTRACT
Qabul qilindi: 20-May 2025 yil
Ma’qullandi: 24-May 2025 yil
Nashr qilindi: 27-May 2025 yil
Background: The dysfunction of the thyroid gland is a
common medical condition. Nowadays, patients
frequently use medicinal herbs as complementary or
alternative options to conventional drug treatments.
These patients may benefit from treatment of thyroid
dysfunctions with Potentilla alba L. preparations. While
it has been reported that Potentilla alba preparations
have low toxicity, nothing is known about their ability
to affect reproductive functions in patients of
childbearing age.
Male Wistar rats were orally treated with a
thyrotrophic botanical drug, standardized Potentilla
alba Dry Extract (PADE), at doses 8 and 40 times
higher than the median therapeutic dose recommended
for the clinical trials, for 60 consecutive days. Male
Wistar rats receiving water (H2O) were used as
controls. After completing treatment, half of the PADE-
treated and control males were used to determine
PADE gonadotoxicity, and the remaining half of PADE-
treated and control males were mated with intact
females. Two female rats were housed with one male
for two estrus cycles. PADE effects on fertility and
fetal/offspring development were evaluated.
KEY WORDS
Herein, we report that oral
treatment of male Wistar rats with
PADE before mating with intact
females instigated marked effects
on male reproductive organs.
Treatment significantly decreased
the motility of the sperm and
increased
the
number
of
pathological
forms
of
spermatozoa. Additionally, a dose-
dependent effect on Leydig cells
was observed. However, these
PADE effects did not significantly
affect male fertility nor fetal and
offspring
development
when
PADE-treated males were mated
with intact females.
Results:
Herein, we report that oral treatment of male Wistar rats with PADE before
mating with intact females instigated marked effects on male reproductive organs. Treatment
significantly decreased the motility of the sperm and increased the number of pathological
forms of spermatozoa. Additionally, a dose-dependent effect on Leydig cells was observed.
However, these PADE effects did not significantly affect male fertility nor fetal and offspring
development when PADE-treated males were mated with intact females.
Introduction.
Thyroid gland dysfunction is one of the most widespread endocrine
disorders globally. In recent years, a growing number of patients have turned to herbal
medicine as either a complementary or alternative approach to managing thyroid-related
conditions. Several medicinal plants have shown modulatory effects on thyroid function. For
instance, Centella asiatica (Gotu Kola),
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Withania somnifera (Ashwagandha), and Commiphora mukul (Guggul) have demonstrated
efficacy in addressing hypothyroidism (Krepkova et al., 2021).
The majority of patients with thyroid dysfunction are female . Our comparative work
has investigated PADE effects on the female reproductive system and fe male PADE treatment
on offspring development, and the study determined that PADE does not significantly affect
the female reproductive system (manuscript in preparation).
Conversely, certain herbs possess thyroid-inhibitory properties, making them
potentially beneficial in the treatment of hyperthyroidism. Among these are Lycopus
virginicus (Bugleweed), Lycopus europaeus (Gypsywort), Melissa officinalis (Lemon Balm),
Rosmarinus officinalis (Rosemary), and Salvia officinalis (Sage) (Krepkova et al., 2021).
Potentilla alba, commonly known as white cinquefoil, is another botanical that has
drawn attention due to its thyrotropic properties. Extracts derived from its rhizomes have
been employed in clinical settings to manage both hypo- and hyperthyroid conditions. These
extracts exhibit a broad pharmacological spectrum, including anti-inflammatory,
antimicrobial, antioxidant, and adaptogenic effects. The plant, native to various regions of
Europe and introduced to the United States, belongs to the Rosaceae family and contains a
range of biologically active compounds such as flavonoids, polyphenols, phenolic acids,
triterpenes, tannins, and polysaccharides (Krepkova et al., 2021).
Despite its therapeutic potential, there is limited data on the reproductive safety of
Potentilla alba, particularly concerning its effects on individuals of reproductive age. This
study aimed to evaluate the impact of a standardized dry extract of Potentilla alba (PADE) on
the male reproductive system and the post-fertilization development of progeny in Wistar
rats.
The dry extract was developed by the All-Russian Institute of Medicinal and Aromatic
Plants (VILAR), consisting mainly of catechins, gallic acid, p-coumaric acid, beta-sitosterol,
and polysaccharides. The preparation contained 61.29% phenolic compounds, 25%
polysaccharides, and 2% phytosterols. Male Wistar rats aged 3 to 4 months were
administered 25 mg/kg and 125 mg/kg of PADE orally for 60 days. The doses corresponded
to approximately 8-fold and 40-fold the median effective clinical dose, respectively (Krepkova
et al., 2021).
Post-treatment evaluation revealed that while the total sperm count remained largely
unaffected, significant decreases were observed in motile sperm percentages and motility
duration, especially in the high-dose group. There was also a dose-dependent rise in the
proportion of spermatozoa with morphological abnormalities. Histological assessments
indicated a marked reduction in the spermatogenesis index and notable alterations in Leydig
cell morphology, including reduced nuclear diameter and increased pyknotic nuclei
(Krepkova et al., 2021)
Table 1. PADE Effect on Male Fertility of Wistar Rats
Group
Mated Females Fertility Index (%) Pregnancy Index (%)
Control (H2O)
17
100
100
PADE 25 mg/kg 18
94.4
100
PADE
125
mg/kg
19
94.7
100
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Table 2. Gonadotoxic Effects of PADE
Parameter
Control
PADE
25
mg/kg
PADE
125
mg/kg
Total sperm count (×10^6)
591.1
±
37.2
599.4 ± 35.5
481.2 ± 54.5
Motile sperm (×10^6)
327.8
±
18.6
240.6 ± 26.6 ** 163.3 ± 29.1 **
Motile sperm (%)
56.1 ± 2.9
46.3 ± 1.7 **
32.8 ± 3.3 **
Motility duration (min)
170.0
±
13.5
162.5 ± 16.0
98.0 ± 11.4
Pathological sperm forms (%)
1.5 ± 0.3
2.7 ± 0.2
5.1 ± 0.5
Testicular weight (g)
3.2 ± 0.1
3.3 ± 0.1
3.4 ± 0.2
Relative testicular weight (%)
0.76 ± 0.04 0.82 ± 0.02
0.90 ± 0.04
Spermatogenesis
index
(median)
3.36
3.08
3.02
Table 3. Leydig Cell Morphometry
Group
Number of Nuclei per Section Median (L25%; U75%)
Control (H2O)
304
24.22 (20.53, 28.33)
PADE 25 mg/kg 242
21.18 (17.41, 24.27)
PADE 125 mg/kg 236
20.22 (17.41, 23.45)
Table 4. Fetal Development on Day 20 Post-Fertilization
Group
Implantations/Dam Live Fetuses/Dam Resorptions/Dam Fetal Weight (g)
Control (H2O)
11.0 ± 0.8
10.2 ± 0.7
0.8 ± 0.3
2.4 ± 0.1
PADE 25 mg/kg
9.9 ± 0.6
9.0 ± 0.3
0.9 ± 0.5
2.3 ± 0.1
PADE 125 mg/kg
10.5 ± 0.6
9.9 ± 0.8
0.6 ± 0.3
2.3 ± 0.1
Table 5. Offspring Development at Day 21 Post-Birth
Group
Pups/Litter at
Birth
Survival at Day
21 (%)
Line
Crossings
Grooming Defecation Rearing
Control
(H2O)
8.6 ± 0.9
100
45.3 ± 1.3
0.9 ± 0.3 1.4 ± 0.3 0
PADE
25
mg/kg
9.3 ± 0.7
100
43.8 ± 3.3
0.9 ± 0.1 2.5 ± 0.5 0.03
PADE
125
mg/kg
11.3 ± 0.6
100
47.9 ± 2.5
0.8 ± 0.2
.8 ± 0.4
0.02
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These findings suggest that although PADE at supratherapeutic doses exerts dose-
dependent gonadotoxic effects in male rats, it does not severely compromise fertility or
offspring viability under the experimental conditions. Nevertheless, the authors caution
against its use in reproductive-age males without further safety profiling. The observed
reproductive toxicity may be attributed in part to phytosterols within the extract, though
catechins and gallic acid could offer protective counter-effects (Krepkova et al., 2021).
Although many medicinal herbs have transient effects on the male reproductive
system, there is a potential risk of impaired spermatogenesis when PADE is used in doses
exceeding the recommended therapeutic doses. This study suggests that PADE treatment of
reproduct ive age men should be avoided or recommended with caution. The doses
prescribed to these patients should not exceed the therapeutic dose. Treating physicians
should consider whether the expected benefits of PADE treatment to the male parent exceed
possible risks to male fertility and reproductive health as well as potential effects on fetal and
offspring development.
In conclusion
, while PADE does not significantly hinder fertilization or early postnatal
development, its impact on spermatogenesis and Leydig cell structure underscores the need
for cautious therapeutic application, particularly in men of childbearing potential. Further
research is warranted to determine the reversibility of these effects and to establish safe
dosage thresholds in humans (Krepkova et al., 2021).
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