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Fulltext Leukemia inhibitory factor: roles in embryo implantation and in nonhormonal contraception

Salleh N, Giribabu N

ScientificWorldJournal, 2014;2014:201514.
PMID: 25152902 DOI: 10.1155/2014/201514

Leukaemia inhibitory factor (LIF) plays an indispensible role in embryo implantation. Aberrant LIF production is linked to implantation failure. LIF regulates multiple processes prior to and during implantation such as uterine transformation into a receptive state, decidualization, blastocyst growth and development, embryo-endometrial interaction, trophoblast invasion, and immune modulation. Due to its critical role, LIF has been a target for a nonhormonal contraception. In this review, we summarize up-to-date information on the role of LIF in implantation and its role in contraception.

Matched MeSH terms: Uterus/physiology
Automated detection of premature delivery using empirical mode and wavelet packet decomposition techniques with uterine electromyogram signals

Acharya UR, Sudarshan VK, Rong SQ, Tan Z, Lim CM, Koh JE, et al.

Comput Biol Med, 2017 06 01;85:33-42.
PMID: 28433870 DOI: 10.1016/j.compbiomed.2017.04.013

An accurate detection of preterm labor and the risk of preterm delivery before 37 weeks of gestational age is crucial to increase the chance of survival rate for both mother and the infant. Thus, the uterine contractions measured using uterine electromyogram (EMG) or electro hysterogram (EHG) need to have high sensitivity in the detection of true preterm labor signs. However, visual observation and manual interpretation of EHG signals at the time of emergency situation may lead to errors. Therefore, the employment of computer-based approaches can assist in fast and accurate detection during the emergency situation. This work proposes a novel algorithm using empirical mode decomposition (EMD) combined with wavelet packet decomposition (WPD), for automated prediction of pregnant women going to have premature delivery by using uterine EMG signals. The EMD is performed up to 11 levels on the normal and preterm EHG signals to obtain the different intrinsic mode functions (IMFs). These IMFs are further subjected to 6 levels of WPD and from the obtained coefficients, eight different features are extracted. From these extracted features, only the significant features are selected using particle swarm optimization (PSO) method and selected features are ranked by Bhattacharyya technique. All the ranked features are fed to support vector machine (SVM) classifier for automated differentiation and achieved an accuracy of 96.25%, sensitivity of 95.08%, and specificity of 97.33% using only ten EHG signal features. Our proposed algorithm can be used in gynecology departments of hospitals to predict the preterm or normal delivery of pregnant women.

Matched MeSH terms: Uterus/physiology*
Fulltext Embryos of the viviparous dermapteran, Arixenia esau develop sequentially in two compartments: terminal ovarian follicles and the uterus

Tworzydlo W, Kisiel E, Bilinski SM

PLoS One, 2013;8(5):e64087.
PMID: 23667700 DOI: 10.1371/journal.pone.0064087

Three main reproductive strategies have been described among insects: most common oviparity, ovoviviparity and viviparity. In the latter strategy, the embryonic development takes place within the body of the mother which provides gas exchange and nutrients for embryos. Here we present the results of histological and EM analyses of the female reproductive system of the viviparous earwig, Arixenia esau, focusing on all the modifications related to the viviparity. We show that in the studied species the embryonic development consists of two "physiological phases" that take place in two clearly disparate compartments, i.e. the terminal ovarian follicle and the uterus. In both compartments the embryos are associated with synthetically active epithelial cells. We suggest that these cells are involved in the nourishment of the embryo. Our results indicate that viviparity in arixeniids is more complex than previously considered. We propose the new term "pseudoplacento-uterotrophic viviparity" for this unique two-phase reproductive strategy.

Matched MeSH terms: Uterus/physiology*
Marantodes pumilum (Blume) Kuntze (Kacip Fatimah) stimulates uterine contraction in rats in post-partum period

Wan Omar WFN, Giribabu N, Karim K, Salleh N

J Ethnopharmacol, 2019 Dec 05;245:112175.
PMID: 31442621 DOI: 10.1016/j.jep.2019.112175

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (Blume) Kuntze has traditionally been used to firm the uterus after delivery, however scientific evidences behind this claim is still lacking.
AIMS OF STUDY: To demonstrate Marantodes pumilum leaves aqueous extract (MPE) has an effect on uterine contraction after delivery and to elucidate the molecular mechanisms involved.
METHODS: Day-1 post-delivery female rats were given MPE (100, 250 and 500 mg/kg/day) orally for seven consecutive days. A day after the last treatment (day-8), rats were sacrificed and uteri were harvested and subjected for ex-vivo contraction study using organ bath followed by protein expression and distribution study by Western blotting and immunohistochemistry techniques, respectively. The proteins of interest include calmodulin-CaM, myosin light chain kinase-MLCK, sarcoplasmic reticulum Ca2+-ATPase (SERCA), G-protein α and β (Gα and Gβ), inositol-triphosphate 3-kinase (IP3K), oxytocin receptor-OTR, prostaglandin (PGF)2α receptor-PGFR, muscarinic receptor-MAChR and estrogen receptor (ER) isoforms α and β. Levels of estradiol and progesterone in serum were determined by enzyme-linked immunoassay (ELISA).
RESULTS: Ex-vivo contraction study revealed the force of uterine contraction increased with increasing doses of MPE. In addition, expression of CaM, MLCK, SERCA, Gα, Gβ, IP3K, OTR, PGF2α, MAChR, Erα and ERβ in the uterus increased with increasing doses of MPE. Serum analysis indicate that estradiol levels decreased while progesterone levels remained low at day-8 post-partum in rats receiving 250 and 500 mg/kg/day MPE.
CONCLUSIONS: These findings support the claims that MPE help to firm the uterus and pave the way for its use as a uterotonic agent after delivery.

Matched MeSH terms: Uterus/physiology
Comparison of relaxin receptors in rat isolated atria and uterus by use of synthetic and native relaxin analogues

Tan YY, Wade JD, Tregear GW, Summers RJ

Br J Pharmacol, 1998 Feb;123(4):762-70.
PMID: 9517397

1. The receptors for relaxin in the rat atria and uterus were investigated and compared by use of a series of synthetic and native relaxin analogues. The assays used were the positive chronotropic and inotropic effects in rat spontaneously beating, isolated right atrium and electrically driven left atrium and the relaxation of K+ precontracted uterine smooth muscle. 2. Relaxin analogues with an intact A- and B-chain were active in producing powerful chronotropic and inotropic effects in the rat isolated atria at nanomolar concentrations. Single-chain analogues and structural homologues of relaxin such as human insulin and sheep insulin-like growth factor I had no agonist action and did not antagonize the effect of the B29 form of human gene 2 relaxin. 3. Shortening the B-chain carboxyl terminal of human gene 1 (B2-29) relaxin to B2-26 reduced the activity of the peptide and removal of another 2 amino acid residues (B2-24) abolished the activity. This suggests that the B-chain length may be important for determination of the activity of relaxin. More detailed studies are needed to determine the effect of progressive amino acid removal on the structure and the bioactivity of relaxin. 4. Porcine prorelaxin was as active as porcine relaxin on a molar basis, suggesting that the presence of the intact C-peptide did not affect the binding of the prorelaxin to the receptor to produce functional responses. 5. Relaxin caused relaxation of uterine longitudinal and circular smooth muscle precontracted with 40 mM K+. The pEC50 values for human gene 2 and porcine relaxins were lower than those in the atrial assay, but rat relaxin had similar pEC50 values in both atrial and uterine assays. Rat relaxin was significantly less potent than either human gene 2 or porcine relaxin in the atrial assay, but in the uterine assay they were equipotent. The results suggest that the relaxin receptor or the signalling pathway in rat atria may differ from that in the uterus.

Matched MeSH terms: Uterus/physiology
Fulltext Diverse roles of prostaglandins in blastocyst implantation

Salleh N

ScientificWorldJournal, 2014;2014:968141.
PMID: 24616654 DOI: 10.1155/2014/968141

Prostaglandins (PGs), derivatives of arachidonic acid, play an indispensable role in embryo implantation. PGs have been reported to participate in the increase in vascular permeability, stromal decidualization, blastocyst growth and development, leukocyte recruitment, embryo transport, trophoblast invasion, and extracellular matrix remodeling during implantation. Deranged PGs syntheses and actions will result in implantation failure. This review summarizes up-to-date literatures on the role of PGs in blastocyst implantation which could provide a broad perspective to guide further research in this field.

Matched MeSH terms: Uterus/physiology
Quercetin interferes with the fluid volume and receptivity development of the uterus in rats during the peri-implantation period

Shahzad H, Giribabu N, Karim K, Kassim N, Muniandy S, Kumar KE, et al.

Reprod Toxicol, 2017 08;71:42-54.
PMID: 28431985 DOI: 10.1016/j.reprotox.2017.04.004

HYPOTHESIS: Quercetin could induce changes to the fluid volume and receptivity development of the uterus during peri-implantation period.
METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment).
RESULTS: Administration of 50mg/kg/day quercetin causes increased in uterine fluid volume and CFTR expression but decreased in γ-ENaC, AQP-5, AQP-9 claudin-4, occludin, E-cadherin, integrin αnβЗ, FGF, Ihh and Msx-1expression in the uterus. Pinopodes were poorly develop, tight junctions appear less complex and implantation rate decreased. Serum estradiol levels increased but serum progesterone levels decreased.
CONCLUSIONS: Interference in the fluid volume and receptivity development of the uterus during peri-implantation period by quercetin could adversely affect embryo implantation.

Matched MeSH terms: Uterus/physiology
Onset of labour

Chong HL, Ong HC, Ang LT

Med J Malaysia, 1974 Sep;29(1):44-53.
PMID: 4282630
Matched MeSH terms: Uterus/physiology
Modulation of sodium-bicarbonate co-transporter (SLC4A4/NBCe1) protein and mRNA expression in rat's uteri by sex-steroids and at different phases of the oestrous cycle

Gholami K, Muniandy S, Salleh N

Res Vet Sci, 2014 Feb;96(1):164-70.
PMID: 24295739 DOI: 10.1016/j.rvsc.2013.11.005

Oestrogen-induced uterine fluid sodium (Na(+)) and bicarbonate (HCO3(-)) secretion may involve SLC4A4. We hypothesized that uterine SLC4A4 expression changes under different sex-steroid influence, therefore may account for the fluctuation in uterine fluid Na(+) and HCO3(-) content throughout the oestrous cycle. The aim of this study is to investigate the differential effects of sex-steroids and oestrous cycle phases on uterine SLC4A4 expression.

Matched MeSH terms: Uterus/physiology*
Expression of proteins related to thyroid hormone function in the uterus is down-regulated at the day of implantation in hypothyroid pregnant rats

Salleh N, Sayem ASM, Giribabu N, Khaing SL

Cell Biol Int, 2019 May;43(5):486-494.
PMID: 30761678 DOI: 10.1002/cbin.11114

Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 μg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRβ-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P

Matched MeSH terms: Uterus/physiology