The actions of thyroxine on the uterus during peri-implantation and implantation periods in rats / Abu Sadat Md. Sayem
Thyroid hormone plays important role in modulating the uterine reproductive events. However, the mechanisms underlying the action of this hormone in the uterus particularly during embryo implantation have not been fully identified. In order to understand these, in this study, effects of thyroxine...
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| Format: | Thesis |
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2018
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| Online Access: | http://studentsrepo.um.edu.my/9188/ http://studentsrepo.um.edu.my/9188/4/PhD_THESIS_FINAL_ASMSayem.pdf |
| Summary: | Thyroid hormone plays important role in modulating the uterine reproductive
events. However, the mechanisms underlying the action of this hormone in the uterus
particularly during embryo implantation have not been fully identified. In order to
understand these, in this study, effects of thyroxine on the uterus during periimplantation
and implantation periods were investigated. These include identifying
changes in the uterine expression of the receptors related to thyroid hormone functions
i.e. thyroid hormone receptor (TR-α and β), thyroid stimulating hormone receptor
(TSHR), retinoic acid receptor (RAR), retinoic X receptor (RXR), vitamin D receptor
(VDR) and extracellular signal-regulated kinase (ERK1/2). Further, changes in
expression of these proteins under the influence of sex-steroids were also identified. In
addition, effects of thyroxine on expression of aquaporins (AQP) protein which is
important in uterine fluid homeostasis and the expression of the proteins related to
uterine receptivity development such as integrin αvβ3, E-cadherin, Msx-1 and Ihh in the
uterus during peri-implantation periods were analyzed. Studies were conducted using
two models: (i) methimazole-induced hypothyroid pregnant rats treated with different
doses of thyroxine (20, 40 and 80 µg/kg/day) and (ii) rats under different sex-steroid
influence (both ovariectomised, sex-steroid replaced and intact at different phases of the
oestrous cycle). Finally, the effects of thyroxine treatment on embryo implantation rate
were determined. Results: In model (i), expression of TRα-1, TRβ-1, RXR and ERK1/2
proteins in the uterus during peri-implantation period increased with increasing doses of
thyroxine. These proteins were found to be distributed in the stroma at a relatively
higher amount following thyroxine treatment. Meanwhile, thyroxine treatment causes
increased in expression of TRα-1, TRβ-1, TSHR, RAR and ERK1/2 proteins and
mRNAs in the uterus during implantation period. Peri-implantation uterus had its
luminal size decrease following treatment with thyroxine with an associated decrease in
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expression of AQP-1, 5 and 7. Thyroxine treatment increases expression of the uterine
receptivity proteins i.e. integrin αvβ3, E-cadherin, Msx-1 and Ihh during periimplantation
period. The numbers of embryo implantation were also found to increase
by thyroxine. In the meantime, treatment of ovariectomised rats with estradiol (E2)
increases the expression of TRα-1, TRβ-1, TSHR, VDR, RAR and ERK1/2 with
expression of these proteins were increased at estrus phase of the oestrous cycle, under
E2 dominance. These proteins were found to be distributed in the uterine luminal and
glandular epithelia and stroma. Following progesterone (P) treatment and at diestrus
phases of the oestrous cycle (under P dominance), expression of these proteins was
lesser as compared to under E2 influence and were found to be distributed only in the
uterine stroma. Conclusions: The changes as documented above could explain the
important role of thyroxine on the uterus during peri-implantation and implantation
periods as well as help to explain the role of sex-steroids in regulating thyroxine
function in the uterus. Dysregulations in these parameters could potentially lead to
infertility |
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