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Sains Malaysiana 47(10)(2018):
2509–2517 http://dx.doi.org/10.17576/jsm-2018-4710-28 Testosterone Down-Regulates
Expression of αvβ3-Integrin,
E-Cadherin and Mucin-1 during Uterine Receptivity Period in
Rats (Testosteron Menindas
Ekspresi αvβ3-Integrin, E-Cadherin
dan Mucin-1 semasa Tempoh
Reseptif Rahim dalam
Tikus) HELMY MOHD MOKHTAR1*,
NELLI
GIRIBABU2
& NAGUIB SALLEH2* 1Department of Physiology, Faculty
of Medicine, Universiti Kebangsaan
Malaysia Medical Center, Jalan Yaacob
Latiff, Bandar Tun
Razak, 56000 Cheras, Kuala Lumpur,
Federal Territory, Malaysia 2Department of Physiology, Faculty
of Medicine, University of Malaya, 50603 Kuala Lumpur, Federal
Territory, Malaysia Diserahkan: 27 Mac 2018/Diterima: 20 Jun 2018 ABSTRACT Adequate
development of uterine receptivity is crucial for establishment
of pregnancy. Expression of uterine receptivity molecules i.e.
αvβ3 integrin, E-cadherin and mucin-1 could be affected
by testosterone. The objective of this study was to investigate
effect of testosterone on expression of these molecules during
early pregnancy. 30 ovariectomised
female Sprague-Dawley rats were divided into 5 groups that consisted
of vehicle control, rats received eight days sex-steroid replacement
regime (intended to mimic the hormonal changes in early pregnancy)
and three groups of rats given testosterone (1 mg/kg/day) subcutaneously
with or without flutamide or finasteride
between day 6 and 8 representing the period of uterine receptivity.
At the end of the treatment, rats were sacrificed and uteri
were removed. Expression and distribution of αvβ3
integrin, E-cadherin and mucin-1 were examined by immunoflourescence
and levels of messenger RNA (mRNAs) were evaluated by real-time
PCR. Expression of αvβ3 integrin, E-cadherin and mucin-1
in the uteri of rats receiving sex-steroid replacement regime
increased significantly as compared to control (p<0.05). In these rats, concomitant administration of testosterone between
day 6 and 8 resulted in expression of αvβ3 integrin,
E-cadherin and mucin-1 to decrease significantly (p<0.05)
as compared to rats receiving sex-steroid replacement regime
without testosterone treatment. Moreover, the testosterone effects
were not antagonized by either flutamide
or finasteride. As a result, reduced expression of uterine receptivity
molecules by testosterone might interfere with early pregnancy
establishment, therefore could adversely affect the female fertility. Keywords: αvβ3 integrin;
E-cadherin; mucin-1; testosterone; uterine receptivity ABSTRAK Perkembangan yang mencukupi
bagi reseptif rahim adalah penting
untuk membolehkan
kehamilan berlaku.
Pengekspresan molekul reseptif rahim
seperti αvβ3 integrin, E-cadherin
dan mucin-1 boleh dipengaruhi oleh testosteron. Objektif kajian ini adalah
untuk mengkaji
kesan testosteron terhadap pengekspresan molekul ini semasa
peringkat awal
kehamilan. 30 ekor tikus Sprague-Dawley yang telah
diovariektomi dibahagikan kepada 5 kumpulan terdiri daripada kumpulan kawalan, kumpulan tikus yang menerima regim penggantian steroid seks selama lapan hari
(bertujuan untuk
meniru perubahan hormon semasa peringkat
awal kehamilan)
dan tiga kumpulan
tikus yang diberikan
rawatan testosteron (1 mg/kg/hari) secara subkulitan
dengan atau
tanpa kehadiran flutamide atau finasteride antara hari ke-6 hingga ke-8 rawatan yang mewakili tempoh reseptif
rahim. Di akhir rawatan,
tikus telah
dikorbankan dan uteri dikeluarkan. Pengekspresan dan taburan αvβ3
integrin, E-cadherin dan mucin-1 ditentukan dengan menggunakan immunoflourescence dan paras mRNA ditentukan dengan menggunakan Real-time PCR.
Pengekspresan αvβ3 integrin, E-cadherin dan
mucin-1 dalam uteri tikus
yang menerima regim
penggantian steroid seks didapati meningkat secara signifikan berbanding kawalan (p<0.05). Pada tikus
ini, pemberian
bersama testosteron antara hari ke-6 hingga hari ke-8 telah menyebabkan pengekspresan αvβ3 integrin, E-cadherin dan mucin-1 menurun dengan signifikan (p<0.05) berbanding
kumpulan yang menerima
regim penggantian steroid seks tanpa rawatan
testosteron. Selain itu,
kesan testosteron
ini tidak ditentang
oleh flutamide
atau finasteride. Kesimpulannya, penurunan
pengekspresan molekul
reseptif rahim
oleh testosteron mungkin mengganggu perkembangan awal kehamilan dan seterusnya
boleh menjejaskan
kesuburan wanita. Kata kunci:
αvβ3 integrin; E-cadherin; mucin-1; reseptif
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