Toll-Like Receptor 9 expression during Mouse Preimplantation Development

In mammals, the innate immune system plays essential roles in maintaining homeostasis through numerous pathways involving Tolllike receptor (TLR) signaling. Pathogen recognition occurs during the first step of innate immunity, which is triggered by the sensing of pattern recognition receptors (PRRs) derived from pathogens. The TLR molecules are flagship members of this system and counteract pathogenic infections in host animals. In mice, the TLR family consists of 12 members (TLR1–9 and TLR11–13). Each member recognizes specific molecular components derived from pathogens. After pathogen recognition, TLRs stimulate downstream signaling pathways to induce type I interferon-α/β (IFN-α/β) and inflammatory cytokine secretion. During mammalian post implantation development, TLRs are expressed in both embryonic and placental tissues in mid and late pregnancy.

In preimplantation development, TLR members were expressed in the cell surfaces in embryos from the 2-cell to blastocyst stages, of which TLR2 and TLR4 were localized mainly in the trophectoderm (TE) of blastocyst. The first differentiation occurs at the blastocyst stage into 2 types of cell lineage: inner cell mass (ICM) and TE. The former mainly generates embryo proper; on the other hand, the latter gives rise to extra embryonic tissue such as placenta. In addition, TE cell-derived trophoblast stem cells (TSCs) expressed Tlr1–6 mRNA but not Tlr9, and also expressed antiviral genes including IFN-β by TLR3 agonist stimuli.

This indicates that TE and TSCs are potent to show antipathogenic responses. On the other hand, certain types of TLRs expressed in embryonic stem cells (ESCs) could not activate downstream signaling pathways to IFN-α/β. Therefore, TLRs appear to show cell type-specific characteristics in ESCs and TSCs. However, there is not enough knowledge about pathogen sensor TLR9 in oocytes and early embryos in mammals.

Genitourinary Injuries | Complete Urethral Injury Associated to Penile Fracture

igorous sexual intercourse was found to be the most common cause of penile fracture. Urethral injury, although rare, may be associated with substantial long-term morbidity such as fistulas and strictures.Immediate surgical approach is recommended by most authors. Immediate surgical intervention has low morbidity, short hospital stay, rapid functional recovery, and no serious long-term sequelae (erectile dysfunction, painful erection, penile deviation or palpable scarring - Scar formation was highly associated with non-absorbable sutures.

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The possibility of urethral injury must always be kept in mind while evaluating such patients. For some authors contrast studies or endoscopic evaluation may prove helpful  while others authors conclude that the management of a penile fracture should not include any further investigation than surgical exploration.So basically, a penis fracture diagnosis is mostly clinical complementary tests, such as ultrasound, are helpful but not definitive. Surgical treatment consists of an incision that allows adequate exposure of the corpora cavernosum and urethra to repair the suspected lesions found upon diagnosis.

Surgical repair has a good functional outcome and low complication rates in the long term. Immediate or delay surgery has been often discussed. Although Kozacioglu et al. published that neither serious deformities nor erectile dysfunction occur as a consequence of a delay in surgery (in patients with no urethral involvement), an immediate surgical approach is strongly recommended.52 years old man presented at emergency room with a clinical suspicious of penile fracture after sexual intercourse.

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Effect of Surgery and Adjuvant Therapy in Reproductive and Sexual Dysfunction

Breast cancer is the most common cancer diagnosed in women and is the second most common cause of cancer-related death, in women, in North America. Approximately 25% of all newly diagnosed breast cancer cases occur among women younger than 50 years of age. Breast cancer is one of the most treatable cancers.

Recent advancements in breast cancer screening, surgical techniques, adjuvant radiation and systemic therapy have resulted in substantial reduction in risk of recurrence and overall- and breast cancer-related mortality. Nevertheless, the cancer treatments cause many acute and chronic adverse effects and are associated with significant impact on quality of life.

Premenopausal women with breast cancer are suffered from many cancer treatment symptoms including fatigue, hot flashes, insomnia, pain, impaired memory, weight gain, menstrual disturbance, vaginal dryness, and are faced with the challenges of sexual dysfunction and impaired fertility.

The symptoms are more pronounced during cancer treatment but can last for several years after completion of the therapy. In this paper we discuss the impact of surgery and adjuvant therapy in reproductive and sexual health of premenopausal women with breast cancer and highlight various treatment options.

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Oxidative Stress Induced Infertility in Varicocele

The pathophysiology of varicocele still remains controversial involving factors like altered testicular thermo-dynamics, changes in testicular blood flow and venous pressure, leydig cell dysfunction and presence of autoantibodies against spermatozoa. Reflux of warm blood from the abdominal cavity into the scrotum, resulting from malfunctioning of valves in spermatic and cremasteric veins attributes to the raised intra-testicular temperature.

Several theories have been proposed for the mechanism involved in defective spermatogenesis because of altered testicular thermodynamics. According to one theory, anatomical disparity between the right and left spermatic veins leads to increased hydrostatic pressure in the left spermatic vein causing dilatation of the pampiniform plexus. Another theory suggests that dysfunctional valves of the internal spermatic veins cause regression of blood. Naughton  proposed that compression of the left renal vein between the superior mesenteric artery and aorta causes partial obstruction of the left spermatic vein leading to varicocele formation. It was also suggested that spermatogenic dysfunction seen in varicocele was the result of thermal damage to spermatozoal proteins and DNA within the seminiferous tubules. The normal anatomical asymmetry and valvular dysfunction causes pooling of blood more in the left spermatic vein.

This phenomenon called the “nutcracker effect” seen as increased compression of the left renal vein between superior mesenteric artery and descending aorta causes retrograde flow of blood down the cremasteric and internal spermatic veins. The right varicocele is considered rare but with the use of modern diagnostic techniques e.g., colored Doppler ultrasound, increased frequency of bilateral localization of varicocele has now been documented in recent studies.

Prognostic Factors of Pregnancy after Homologous Intrauterine Insemination

Intrauterine insemination (IUI) is the first-choice method in the treatment of infertility due to moderate oligoasthenoteratozoospermia, ovulatory dysfunction, surgically treated stage I or stage II endometriosis, cervical and unexplained infertility, when at least one fallopian tube is patent. Studies report variable pregnancy (PRs) and delivery (DRs) rates, and outline many IUI outcome predictors in often large retrospective series or reduced prospective studies.

The type and extent of fresh sperm quality impairment, motility, and sperm morphology, and inseminated motile sperm count (IMC) after sperm preparation are often the most important sperm parameters that predict IUI success. However, the IMC threshold level, above which IUI can be performed with acceptable PRs has not been determined yet. Other important male factors of influence are sexual abstinence before IUI, 

Technique of processing fresh sperm, sperm quality as assessed by computer-assisted sperm analysis, abnormal hemizona assay, abnormal ionophore-induced acrosome reaction, post-wash total sperm count, sperm preparation time, the means for prepared sperm insertion into the female genital tract, time and number of inseminations, and immediate absolute rest after IUI. 

Female positive predictors for successful IUI are women’s age ≤38 years, good ovarian reserve, higher number of antral and mature follicles developed, increased endometrial thickness, and good endometrial and subendometrial vascularization. Female factors influencing PRs negatively are longer duration of infertility and primary infertility, high number of cycles performed, and the use of alcohol, coffee, and tea in the past

Role of Male Factor Testing in Recurrent Pregnancy Loss or In Vitro Fertilization Failure

The appropriate management for male partners of couples with recurrent pregnancy loss (RPL) or recurrent implantation failure during in vitro fertilization (IVF) remains unclear. In particular, men with normal semen parameters are often ignored because the “bulk semen parameters” appear normal. Despite normal semen parameters, male partners in couples with RPL or recurrent implantation failure could have underlying genetic abnormalities in sperm DNA that can be identified. There are a couple of diagnostic tests that we recommend in the evaluation of these men, the first being DNA Fragmentation Index (DFI) and the second, fluorescence in situ hybridization (FISH) for evaluating sperm aneuploidy.

DNA fragmentation occurs due to abnormal packaging of sperm chromatin. Unlike somatic cells that utilize histones as the primary packaging of chromatin, sperm utilize protamines. First, approximately 85% of histones are replaced by protamines, tightly winding chromatin into structures called toroids. In the epididymis, protamines are further compacted by disulfide bond cross-linking. Sperm becomes susceptible to damage if packing with protamines is incomplete.

 In particular, there are no repair mechanisms that occur once sperm are transported to the epididymis or post ejaculation High DNA damage as demonstrated by increased DFI is associated with recurrent pregnancy loss, recurrent IVF failure, and increased congenital abnormalities. Therefore, men with abnormally elevated DFI can undergo testicular biopsy for sperm retrieval and use with intracytoplasmic sperm injection (ICSI) because DFI in testicular sperm is significantly lower compared to DFI in ejaculated sperm. 

There are several DFI assays available, and each has its own set of advantages and disadvantages. The sperm chromatin structure assay (SCSA) is commercially available, but the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay, Halo test, and Comet assay are other options.

Antenatal Care Utilization in Debre Tabor, North West Ethiopia

Antenatal care (ANC) is a care given for pregnant woman before delivery in order to promote health of mother and fetus. It helps to cope with problems by making early detection and providing appropriate care and treatment. Antenatal care is one of the pillars of the Safe Motherhood Strategies that increases the chance of using a skilled attendant at birth; which in turn can reduce maternal morbidity and maternal mortality .

Globally millions of women and newborns suffer from illness related to pregnancy and childbirth each year with 800 women die every day. In 2010 alone, there were an estimated of 287000 maternal deaths, of which 99% occurred in developing regions, 56% of maternal deaths were occurred in Sub-Saharan Africa. Worldwide, adult lifetime risk of maternal mortality rate was 1 in 180. The intended objective of achieving the Millennium Development Goal (MDG) was not met; especially in sub-Saharan Africa. Most of maternal deaths which are occurred in sub Saharan Africa could have been prevented by increasing the utilization of maternity care. Unexpected high maternal mortality in developing countries is due to both the nonavailability of services and poor utilization the available services.

According to Ethiopian Demography and Health Survey (EDHS) 2011 results, the maternal mortality ratio (MMR) for Ethiopia was 676 deaths per 100,000 live births, which is nearly the same with EDHS 2005. In 2010, the maternal death was estimated to be 350 per 100,000 live births and the lifetime risk of maternal mortality was 1 in 67. The percentage change in MMR between 1990 and 2010 was 64.The ANC coverage of Ethiopia was 34%, out of which 11% of the users got it during first trimester and 19% received the recommended four or more ANC visits. In Amhara region, only 33.6% women were receiving antenatal care from a skilled provider, 7% from health extension worker, while 59.1% did not receive it at all.

We assessed the association of dependent and independent variable by using simple regression model followed by multiple regression models. Our simple logistic analysis showed that educational status, occupation, planned pregnancy, perceived importance of antenatal care, monthly family expenditure, women’s decision-making power, experience of abortion and stillbirth and knowledge of mother on pregnancy related health problems showed significance association. Then we put variables those showed p-value of <0.25 into multiple logistic regression model to rule out confounder/s. The result of multiple analysis showed that educational status of the mother, her occupation, household’s monthly income, mother’s perception, planning of pregnancy, mother’s empowerment and prior experience of stillbirth had significant association with ANC utilization.

Necrotizing Enterocolitis in Rat Offspring Exposed to Placental Insufficiency: Role of Aldosterone, Oxidative Stress and Leptin

NEC is an acute inflammatory disease of the intestine of neonates and can result in intestinal necrosis, systemic sepsis and multi-system organ failure. The incidence of NEC is inversely related to birth weight and gestational age, and when intestinal necrosis is already stablished the process is rarely reversible and mortality rates can reach up to 50-80% in severe cases. Despite, the effort of physicians and researchers the morbidity and mortality of NEC have increased in the last decade, with more severe complications and poor response to treatment. This is partially explained by the improvement in health care practices to maintain alive premature infants, but it does not explain individual differences in outcomes within the same institutional setting. One of the factors involved in infant’s susceptibility to develop NEC is perinatal morbidity, which is strongly associated with fetal-placental unit function. Currently, there are no identified factors linking placental function and the risk to develop NEC; therefore, identification of these factors could help to develop perinatal preventive strategies to decrease the morbidity and mortality associated with NEC.

Experimental and epidemiological studies suggest a multifactorial etiology for NEC including predisposing factors such as enteral feeding, hypoxia and or hypothermia, but with unclear pathogenesis. We induced NEC in premature low birth weight (LBW) rat’s offspring from a rat model of placental insufficiency. Premature birth is the major determinant of NEC. Increased oxidative stress is among the factors associated with NEC in premature infants. Oxidative stress has been observed in several maternal conditions associated with placental insufficiency. Experimental studies report a direct correlation between increased oxidative stress and Aldosterone plasma levels in newborns.

 Moreover, epidemiological studies reported increases in plasma aldosterone levels associated with LBW and preterm delivery. Aldosterone can regulate oxidative stress, hence it can be suggested that increased levels of aldosterone and oxidative stress may be associated with NEC in premature and low birth weight infants exposed to placental insufficiency. Aldosterone is involved in the developmental changes of Na+ electrogenic transport in immature intestines , resulting in alteration in the homeostasis of gastrointestinal mucus barrier, and abnormal microbial colonization of the gastro intestinal tract with exacerbated inflammatory response and necrosis. The digestive and absorptive capacity of the gastrointestinal tract is also compromised in premature infants.

Experimental studies report that postnatal leptin treatment enhances digestive function in intrauterine growth restricted offspring, by increasing cell mitosis and promoting growth of intestinal mucosa. Leptin levels were reduced in animal models of placental insufficiency induced by reduced uterine perfusion. Therefore, leptin levels at birth could be associated with growth capacity and maturation of gastrointestinal tract in newborns.

Fetomaternal Hemorrhage: A Review after a Case Report

Fetomaternal hemorrhage (FMH) consists in the transmission of fetal blood cells into the maternal circulation. Although the pathophysiology is not yet completely understood, it is likely to occur in small volumes in all pregnancies, with no apparent clinical significance in most cases. The incidence of clinically significant fetomaternal hemorrhage varies widely depending on the cutoff used to define it  Considering only the volume lost is probably insufficient as the rate of blood loss is also an important factor. Many studies defined 30 mL as threshold for meaningful fetal blood volume and 80 mL or 150 mL as cutoff to define “large” or “massive” fetomaternal bleeds . Massive fetomaternal hemorrhage is more likely to be fatal if blood loss occurs over minutes rather than hours, days, or weeks.

The blood pressure is higher in placental blood vessels than in the intervillous space. If the maternal-fetal barrier is disrupted, hemorrhage will occur from the fetus to the maternal circulation. Incidence increases with gestational age, and so does the volume of fetal blood in the maternal circulation. Some risk factors such as external cephalic version, abdominal trauma, manual removal of the placenta, placental abruption, monochorionic monoamniotic twins, preeclampsia, placental tumors, and amniocentesis have been associated with fetomaternal hemorrhage. However, no cause is identified in over 80% of cases.

Recognizing the bleed before it becomes significant requires a high index of suspicion as the triad of decreased fetal movement, sinusoidal heart rate, and hydrops fetalis corresponds to a group of symptoms of severe anemia associated with massive fetomaternal hemorrhage. In some situations, such as unexplained stillbirth, persistent maternal perception of decreased fetal activity, hydrops, unexplained elevated middle cerebral artery Doppler, testing for fetomaternal hemorrhage should be considered. Amongst the different diagnostic tests available, the Kleihauer-Betke is a quantitative test based on the principle that hemoglobin F (HbF) is relatively resistant to acid elution compared with the hemoglobin of adult erythrocytes.

When a massive fetal hemorrhage occurs it is crucial to promptly detect it. Immediate cesarean delivery is recommended if the infant is near-term gestation. In cases of preterm gestation, in utero transfusion can be considered to minimize the effects of fetal anemia. If untreated, the effects of fetomaternal hemorrhage can be catastrophic, potentially resulting in cardiac failure, hydrops, hypovolemic shock, intrauterine demise, neonatal death, neurologic injury, cerebral palsy or persistent pulmonary hypertension

Folic Acid Supplementation in Prevention of Neural Tube Defects

Neural tube defects (NTDs) are congenital anomalies (CAs) of the central nervous system. They are the most common birth defects along with congenital heart anomalies (CHAs) and anomalies of urinary system. EUROCAT (European Surveillance of Congenital Anomalies) reported that a total prevalence of major congenital anomalies was 23.9 per 1000 births in the period 2003-2007. CHAs were the most common non-chromosomal subgroup (6.5/1000), followed by limb defects (3.8/1000), anomalies of urinary system (3.1/1000) and nervous system anomalies (2.3/1000).

CAs are a special category of human disorders due to their very early onset and defect condition. Therefore there is a limited chance for complete prevention of it. NTDs are the most frequent CAs of the central nervous system. However, this has been a great progress in the prevention of NTDs with periconceptional folic acid (FA) or FA containing multivitamins (MVs). NTDs is defined as a group of severe CAs of the central nervous system resulting from failure of the neural tube to close during neurulation between 20 and 28 days after conception. Wide world, the birth prevalence of NTDs (spina bifida and anencephaly) varies among different populations. In some areas, such as Northern China, the prevalence is very high (1/200).

The neurulation is major step in brain development, who involves the formation of the first well-defined neural structure (neural tube). The neural tube forms during the third week of gestation (20-28 day). The neurulation is the embryonic process that leads to the ultimate development of the neural tube. 

This process can be divided into two phases:

Primary neurulation (3–4 week): involves the formation of the brain and neural tube from the caudal region to the upper sacral level. This phase of neurulation is associated with open NTDs and result in conditions including anencephaly, myelomeningocele (open spina bifida) and craniorachischisis.

Secondary neurulation completes the distal sacral and coccygeal regions. Disruption of secondary neurulation results with skin covering lesion sites of the spinal cord structure such as asymptomatic spina bifida occulta and severe spinal cord tethering are classed as closed NTDs.