Reproductive Tract Abnormalities Research Articles

The use of hysteroscopy to identify and treat reproductive tract abnormalities in the mare

SummaryHysteroscopy is a complementary tool to the traditional transrectal palpation and ultrasonography commonly performed by equine practitioners. Once mastered, it is a quick and useful diagnostic tool for the general and targeted evaluation of the endometrium and provides real time information about potential causes of subfertility. Samples of intrauterine fluid and the endometrium can be taken via transendoscopic catheters or infusion pipettes or via the use of traditional endometrial biopsy forceps. In addition to being a useful diagnostic tool, treatments can often be performed at the same time the pathologies are identified, providing mare owners with information and resolution of problems. With the development of additional technologies, hysteroscopy allows for optical biopsies to be performed, which will likely increase in use as the software moves from the research laboratories to clinical practice. Hysteroscopy is an easily learned, useful clinical skill for the identification of abnormalities in the mares' reproductive tract.

Genome Sequence Comparisons between Small and Large Colony Phenotypes of Equine Clinical Isolates of Arcanobacterium hippocoleae.

Arcanobacterium hippocoleae is a Gram-positive fastidious bacterium and is occasionally isolated from the reproductive tract of apparently healthy mares (Equus caballus) or from mares with reproductive tract abnormalities. Apart from a few 16S rRNA gene-based GenBank sequences and one recent report on complete genome assembly, detailed genomic sequence and clinical experimental data are not available on the bacterium. Recently, we observed an unusual increase in the detection of the organism from samples associated with mare reproductive failures in Atlantic Canada. Two colony morphotypes (i.e., small, and large) were detected in culture media, which were identified as A. hippocoleae by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. Here, we report the whole genome sequencing and characterization of the morphotype variants. The genome length of the large phenotypes was between 2.42 and 2.43, and the small phenotype was 1.99 Mbs. The orthologous nucleotide identity between the large colony phenotypes was ~99%, and the large and small colony phenotypes was between 77.86 and 78.52%, which may warrant the classification of the two morphotypes into different species. Phylogenetic analysis based on 16S rRNA genes or concatenated housekeeping genes grouped the small and large colony variants into two different genotypic clusters. The UvrA protein, which is part of the nucleotide excision repair (NER) system, and 3-isopropoylmalate dehydratase small subunit protein expressed by the leuD gene were identified as potential virulence factors in the large and small colony morphotypes, respectively. However, detailed functional studies will be required to determine the exact roles of these and other identified hypothetical proteins in the cellular metabolism and potential pathogenicity of A. hippocoleae in mares.

Environmental Chemical Exposure Research and Characteristics of Study Subjects Recruited from Midwifery vs. Hospital Based Clinics

Exposure to environmental contaminants during pregnancy is thought to play a role in the reported increase in developmental abnormalities of the male reproductive tract and rise in the rates in testicular cancer among young men as well as increasing prevalence of allergy, asthma, obesity, and diabetes in the general population. Traditional epidemiological studies have recruited pregnant women from hospital clinics, delivery wards or physician offices. Recruitment of expectant mothers from midwifery clinics is being employed in ongoing studies and comparison of study subject characteristics suggests that there are no important differences in the socio- economic indicators. Hence we suggest that midwives have an important role to play in future epidemiological studies designed to determine the health consequences of exposure to environmental contaminants.

Role for Nongenomic Estrogen Signaling in Male Fertility.

Estrogen actions are mediated by both nuclear (n) and membrane (m) localized estrogen receptor 1 (ESR1). Male Esr1 knockout (Esr1KO) mice lacking functional Esr1 are infertile, with reproductive tract abnormalities. Male mice expressing nESR1 but lacking mESR1 (nuclear-only estrogen receptor 1 mice) are progressively infertile due to testicular, rete testis, and efferent ductule abnormalities similar to Esr1KO males, indicating a role for mESR1 in male reproduction. The H2NES mouse expresses only mESR1 but lacks nESR1. The goal of this study was to identify the functions of mESR1 alone in mice where nESR1 was absent. Breeding trials showed that H2NES males are fertile, with decreased litter numbers but normal pup numbers/litter. In contrast to Esr1KO mice, H2NES testicular, and epididymal weights were not reduced, and seminiferous tubule abnormalities were less pronounced. However, Esr1KO and H2NES males both had decreased sperm motility and a high incidence of abnormal sperm morphology. Seminiferous tubule and rete testis dilation and decreased efferent ductule epithelial height characteristic of Esr1KO males were reduced in H2NES. Consistent with this, expression of genes involved in fluid transport and ion movement that were reduced in Esr1KO (Aqp1, Car2, Car14, Cftr) were partially or fully restored to wild-type levels in H2NES. In summary, in contrast to Esr1KO males, H2NES males are fertile and have reduced phenotypic and functional abnormalities in the testis and efferent ductules. Thus, mESR1 alone, in the absence of nESR1, can partially regulate male reproductive tract structure and function, emphasizing its importance for overall estrogen action.

Delayed Puberty.

Testicular volume ≥4ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or menarche by 15 y in girls and absence of testicular enlargement by 14 y in boys. Delayed puberty can be due to hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism or eugonadotrophic eugonadism characterised by low, elevated and normal gonadotrophin levels, respectively. Constitutional Delay of Growth and Puberty (CDGP) and systemic illness should be considered before pathological causes. Assessment of sexual maturity by Tanner's staging and anthropometric assessment on growth chart is pivotal. Lack of menarche in girls with thelarche suggests structural abnormalities of reproductive tract or disorders of sexual development. Measurement of bone age helps to interpret hormone measurements and decide on timing of pubertal induction. Ultrasound assessment of abdomen gives valuable clues to pubertal onset (in girls) and possible underlying etiology. Karyotyping is mandatory in all girls with delayed puberty and short stature, and delayed menarche and boys with hypergonadotrophic hypogonadism. Gonadotrophin releasing hormone analogue stimulation test may help distinguish hypogonadotrophic hypogonadism from CDGP. Pubertal induction is done with intramuscular testosterone and oral estradiol in boys and girls, respectively. Hormone replacement is begun at low doses and slowly escalated over 2 y to mimic a physiological puberty process. Short course of testosterone for 3 to 6 mo is helpful in adolescent boys with CDGP and psychological distress. Attainment of adult sexual maturity by 18 y is mandatory to rule out disorders of hypothalamic pituitary gonadal axis.

Vaginal atresia in a patient with uterus didelphys

Background: Female reproductive tract abnormalities are generally encountered in 4%-7% of women. Various combinations have been described in the literature. Our case reports a rare female genital tract anomaly of the distal vagina combined with uterus didelphys. Case Presentation: A 15-year-old girl with lower vaginal atresia associated with uterus didelphys presented with cyclical progressively worsening abdominal pain and primary amenorrhea. Pelvic ultrasound (US) and magnetic resonance imaging (MRI) illustrated two separated uterine cavities associated with a distended fluid-filled structure ending in a blind pouch at the lower margin of the vagina. Conclusion: The presence of congenital anomalies of the female urogenital system may be suspected in the case of cyclical abdominal pain in young girls with primary amenorrhea. The use of US as a primary approach is recommended. MRI is preferred to specify the height and extent of vaginal aplasia as long as to guide the choice of the most appropriate surgical technique.

Clinical and Genetic Characteristics of a Cohort with Distal Vaginal Atresia

Distal vaginal atresia is a rare abnormality of female reproductive tract in which the vagina is closed or absent. The distal vagina may be replaced by fibrous tissue and the condition is often not diagnosed until a girl fails to begin having periods at puberty. Although it is a congenital disorder, potential genetic causes of distal vaginal atresia are still unknown. We recruited a cohort of 39 patients with distal vaginal atresia and analyzed their phenotypic and genetic features. In addition to the complaint of distal vaginal atresia, approximately 17.9% (7/39) of the patients had other Müllerian anomalies, and 17.9% (7/39) of the patients had other structural abnormalities, including renal-tract, skeletal and cardiac anomalies. Using genome sequencing, we identified two fragment duplications on 17q12 encompassing HNF1B and LHX1, two dosage-sensitive genes with candidate pathogenic variants, in two unrelated patients. A large fragment of uniparental disomy was detected in another patient, affecting genes involved in cell morphogenesis and connective tissue development. Additionally, we reported two variants on TBX3 and AXL, leading to distal vaginal atresia in mutated mouse model, in our clinical subjects for the first time. Essential biological functions of these detected genes with pathogenic variants included regulating reproductive development and cell fate and patterning during embryogenesis. We displayed the comprehensive clinical and genetic characteristic of a cohort with distal vaginal atresia and they were highly heterogeneous both phenotypically and genetically. The duplication of 17q12 in our cohort could help to expand its phenotypic spectrum and potential contribution to the distal vaginal atresia. Our findings of pathogenic genetic variants and associated phenotypes in our cohort could provide evidence and new insight for further research attempting to reveal genetic causes of distal vaginal atresia.

Clinical and Histological Features of Ovarian Hypoplasia/Dysgenesis in Alpacas.

Alpacas have a high incidence of congenital reproductive tract abnormalities, including ovarian hypoplasia/dysgenesis. Diagnosis of this condition is often challenging. The present study describes the clinical, ultrasonographic, and histologic features of ovarian hypoplasia/dysgenesis syndrome in 5 female alpacas. Additionally, serum AMH levels were compared between female alpacas diagnosed with ovarian hypoplasia/dysgenesis and a group of reproductively sound females (n = 11). The syndrome was suspected based on the presence of an infantile uterus and lack of ovaries by ultrasonography and laparoscopy. All females had normal female karyotype (n = 74 XX), but one presented a minute chromosome. The ovaries from these cases showed 3 main histological classifications: hypoplasia (n = 2), dysgenesis (n = 2), and dysplasia (n = 1). Serum AMH levels in affected females were significantly lower (P < 0.05) than those of reproductively sound control females. In conclusion, Serum AMH level may be helpful in the rapid diagnosis of ovarian hypoplasia/dysgenesis syndrome in alpacas. Furthermore, this syndrome in alpacas presents a variety of histological features. Different mechanisms may be involved in the derangement of ovarian differentiation. Further studies are needed to elucidate the causes of the syndrome.

Clinical utility of abdominal multidetector CT in 85 goats with suspected abdominal disease.

Diagnosing the cause of abdominal disease in goats can be challenging. Clinical history, physical investigation, and laboratory findings do not always allow definitive identification of intra-abdominal disease or the underlying cause. Multidetector CT (MDCT) has become more readily available and now often replaces or augments other abdominal imaging techniques. The objective of this retrospective, observational, descriptive study was to investigate the clinical utility of MDCT for evaluation of the abdomen in goats with suspected abdominal disease involving the urinary, gastrointestinal, reproductive tracts and abdominal wall. Medical records (1/2009-12/2017) were reviewed for all goats undergoing an abdominal MDCT. Signalment, clinical history, examination and MDCT findings and outcome were recorded and categorized by abdominal organ system and wall lesion. Clinical problems and MDCT findings were compared in the various abdominal categories. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (OR) were calculated for MDCT, using clinical examination findings as the reference standard. A total of 85 goats underwent an abdominal MDCT examination. The sensitivity of MDCT for detecting urinary, gastrointestinal, reproductive tract, and abdominal wall abnormalities in goats with clinical problems related to these body systems was high at 94.7 %, 78.3%, 94.1%, and 100%, and the specificity was high at 95.6%, 96.7%, 93.9%, and 100%, respectively. The PPV was 94.7%, 90.0 %, 80.0%, and 100.0%, the NPV was 95.6%, 92.1%, 98.4%, and 100%, and the OR were 387.0, 104.4, 248.0, and infinite. In conclusion, findings supported the use of MDCT as an adjunct diagnostic test for assessing goats with abdominal disease.

Токсичний вплив кадмію на репродуктивну функцію чоловіків

The purpose of the review of foreign literature was to analyze current research on the effects of cadmium on male reproductive function. Results. According to the researcher data, at least 15–20% of cases of fertility decline in males fall on infertility. The etiology of this phenomenon in 50% of cases remains unknown, however, increasing environmental pollution contributes to a constant increase in male infertility. One of the most toxic pollutants is cadmium. Numerous animal model studies and human epidemiological studies indicate an adverse effect of cadmium on male fertility. Smoking is an important source of cadmium, which is absorbed into the human body. In vitro studies confirm the deleterious effects of cigarette smoke compounds on sperm motility and spermatozoon parameters. Depending on the concentration, nicotine suppresses the progressive motility of the spermatozoon parameters, starting from the lowest concentration used (1 ng/ml). Likewise, it decreases the percentage of viable spermatozoon parameters and increases the amount of spermatozoon parameters in late apoptosis with altered chromatin compactness or DNA fragmentation already after 3 hours of incubation. On average, the daily intake of cadmium in humans is 1.06 μg/kg body weight, the half-life of cadmium is more than 20-40 years, which causes its accumulation in the body. The testicles are the organ in which cadmium is stored in large quantities. Studies have shown that the testicles are extremely sensitive to cadmium because these organs are characterized by intense cellular activity, where vital spermatogenesis processes take place. Exposure to cadmium leads to reproductive tract abnormalities such as cryptorchidism and hypospadias, testicular cancer, subfertility or infertility, called testicular dysgenesis syndrome. In the genesis of the testicles during the embryonic and neonatal periods, Sertoli’s cells play a critical role, the development of which is influenced by cadmium. Exposure to cadmium (1-2 mg/kg, subcutaneously) in pregnant and lactating rats causes vacuolization of Sertoli’s cells and loss of cells in the epithelium of the seminiferous tubules in adult animals. Cadmium inhibits proliferation, induces apoptosis and DNA damage in immature Sertoli’s cells. Perinatal exposure to cadmium affects the development and function of fetal Leydig cells, which are endocrine cells in the testicle. In pregnant rats that received a single dose of cadmium (0.25, 0.5, and 1.0 mg/kg, intraperitoneally), synthesis of testosterone in the fetal tests was significantly reduced, while gene expression in cells was suppressed, and the androgen-dependent formation process was reduced. The mechanism by which cadmium mediates impaired male fertility is also associated with the production of reactive oxygen species in the testicles, which leads to oxidative stress that interferes with the development and functioning of the spermatozoon parameters. Exposure to cadmium, for both environmental and occupational reasons, can contribute to a decrease in the quality of human sperm, which confirms high toxicity of cadmium. Conclusion. Thus, in humans and other mammals, cadmium damages the male reproductive system, disrupts its structure, including the vascular system of the testicles, leads to DNA damage, inhibits functions of germ cells, leads to loss of sperm quality and quantity, sub-fertility or infertility

Assessment of anti-Müllerian hormone in mares’ transitional period and in relation to fertility in elderly mares

Anti-Müllerian Hormone (AMH) has been linked to reproductive tract abnormalities in mares and stallions. This study aimed at evaluating AMH as a biomarker for two reproductive conditions in mares. In the first part of this study, plasma AMH was evaluated as an early indicator of the onset of cyclicity in mares in the transitional period from the anovulatory phase during winter anoestrus to the cyclic phase during the breeding season. Ten mares between 8 and 17 years old were included in the experiment which lasted from mid-February until the end of April. Ovarian activity was monitored with ultrasonography three times per week, the detection of a corpus haemorrhagicum/luteum was documented and antral follicle counts (AFC) were recorded. Blood samples were collected weekly by jugular venipuncture during the whole study period to compare AMH concentrations before and after the first ovulation of the year. The second objective was to evaluate if plasma AMH concentrations in middle-aged mares are linked to fertility and could serve as a prognostic marker in that age group. A total of 41 privately-owned clinically sound mares aged between 12 and 21 years of various breeds were inseminated with fresh or frozen semen. Mares were scanned between day 14 and 20 and the “early pregnancy rate” included only positive pregnancy examinations after the first observed cycle in the season of each mare. Potential associations between the early pregnancy rate in the first cycle and the explanatory factors AMH concentrations, age, status of the mare, stud, development of post-breeding endometritis, number of inseminations and semen type were analysed using logistic regression models. In the first part of the study, correlation between AMH and AFC for the whole study period (P = 0.0002, ρ = 0.55) as well as prior to (P = 0.008, ρ = 0.58) and after the first ovulation (P = 0.0007, ρ = 0.69) were observed. However, AMH concentrations before and after the first ovulation of the year were not statistically different. The second part of the study revealed no association between early pregnancy rate and AMH concentrations or any of the other mentioned factors. In conclusion, this study showed no evidence of a difference between AMH concentrations before and after the first ovulation of the year thus not supporting the use of AMH as a biomarker to predict the onset of cyclicity in mares. We could furthermore not show a relationship between plasma AMH concentrations and early pregnancy rates in this cohort of animals.

Increasing the efficiency of the herd reproduction system by introducing innovative technologies into dairy farming in Northern Kazakhstan.

Background and Aim:In recent years, Kazakhstan has increasingly imported breeding cows for dairy and beef production. To maintain and improve their breeding qualities of reproductive function, it is necessary to constantly monitor the herd reproduction system. The aim of this study was to increase the level of herd reproduction by introducing innovative technologies into dairy farms in Northern Kazakhstan. To achieve this goal, the AlphaVision visual insemination system (IMV Technologies, France) was used, aiding to improve the artificial insemination method in farms in Northern Kazakhstan and increased the breeding rate using sexed semen to inseminate cows. In addition, the AlphaVision device was used in the differential diagnosis of certain diseases of the reproductive organs of cows.Materials and Methods:The object of the study was 200 cows (3-5-year-old) and 100 heifers (16-18-month-old) of Holstein breed. The authors carried out a comparative analysis of biotechnological methods of reproduction – the cervical method insemination with rectal fixation of the cervix (traditional method of insemination) and the AlphaVision visual insemination system, and the effectiveness of AlphaVision for diagnosing some reproductive tract abnormalities in cows was studied. In the experiment on conducting artificial insemination through AlphaVision, we have used both normal (two-sex) and sexed semen.Results:When using the AlphaVision visual insemination system, a higher percentage of fruitful insemination was noted (20.7%) than when using the traditional method. The images obtained with AlphaVision made it possible to identify cows with abnormal sexual cycles, signs of vaginitis, endometritis, cervicitis, and differentiate them by the nature of the exudate. In many cases, visual examinations of the vagina and cervix are not carried out before the traditional method of artificial insemination. For this reason, some vaginal and cervical abnormalities are not diagnosed, resulting in reduced fertility in cows. We have found that the number of genital abnormalities has increased by 30% with the increasing age of cows. Obstetric and gynecologic pathologies in high-yielding cows are noted in more than 50% of the herd. A comparative assessment of clinical manifestations of cervicitis and other pathologies of reproductive organs, using the AlphaVision visual insemination system, has been carried out for the identified diseases. With the traditional method of insemination with conventional semen, the calf yield per 100 cows for the period 2016-2019 has been 65-80% and with sexed semen 30-50%. With AlphaVision in 2020, the insemination rate was 85% conventional and 60% sexed, respectively, which was 5% and 10% higher than with conventional insemination. This was due to the improved diagnosis of some reproductive diseases in cows.Conclusion:The introduction of innovative technology, namely, the visual insemination system AlphaVision, into the practice of dairy farms in Northern Kazakhstan increased the level of the herd reproduction system.

Phthalate Toxicity in Rats and Its Relation to Testicular Dysgenesis Syndrome in Humans.

This work describes the relevance of toxicology studies of environmental chemicals, with a focus on phthalates, for a hypothesis that certain human male reproductive disorders and diseases have a common etiology of disturbance of normal development in utero. The "Testicular Dysgenesis Syndrome" hypothesis in humans has parallels in male reproductive tract abnormalities and microscopic lesions reported for phthalate toxicity in rats. Additionally, this work describes the histological findings of abnormal testicular development (testicular dysgenesis) in rats as compared to those in humans, as well as potential findings in rats at different ages, from the embryo to the adult.

Homozygous WNT9B variants in two families with bilateral renal agenesis/hypoplasia/dysplasia.

WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. To our knowledge, WNT9B has not been associated with renal defects in humans; however, WNT9B-/- mice have renal agenesis/hypoplasia and reproductive tract abnormalities. We report four individuals from two unrelated consanguineous families with bilateral renal agenesis/hypoplasia/dysplasia and homozygous variants in WNT9B. The proband from Family 1 has bilateral renal cystic dysplasia and chronic kidney disease. He has two deceased siblings who presented with bilateral renal hypoplasia/agenesis. The three affected family members were homozygous for a missense variant in WNT9B (NM_003396.2: c.949G>A/p.(Gly317Arg)). The proband from Family 2 has renal hypoplasia/dysplasia, chronic kidney disease, and is homozygous for a nonsense variant in WNT9B (NM_003396.2: c.11dupC/p.(Pro5Alafs*52)). Two of her siblings died in the neonatal period, one confirmed to be in the context of oligohydramnios. The proband's unaffected brother is also homozygous for the nonsense variant in WNT9B, suggesting nonpenetrance. We propose a novel association of WNT9B and renal anomalies in humans. Further study is needed to delineate the contribution of WNT9B to genitourinary anomalies in humans.

Ovarian inactivity in female dromedary camels

The present study describes a clinical trial aimed at understanding the causes of ovarian inactivity among female dromedary racing camels in the United Arab Emirates. A total of 1406 female racing camels were presented to the Aljazeera Veterinary Center during a 19-month period from September 2014 to April 2016 because of repeat breeding (as identified by camel owners). Females underwent ultrasonographic examination of the reproductive tract, as well as a manual vaginal examination. Any observed reproductive tract abnormalities were record. A percentage of 23.8 of females possessed no detectable reproductive tract abnormalities (and thus were diagnosed as typical repeat breeders). Of the remaining 76.2% of females, 59% had utero-tubal abnormalities and 41% had ovarian afflictions. The incidences of ovarian and utero-tubal affections in nulliparous and parous infertile females were 66.7 % versus 33.3 % (P&lt;0.05) and 32.2% versus 67.8% (P&lt;0.05), respectively. Most of the ovarian affections were due to ovarian inactivity or ovario-hydrobursitis. The incidence of ovarian inactivity and ovarian hydro-bursitis in nulliparous and parous females were 57.6% versus 13.2% (P&lt;0.05) and 5.8% versus 18.1% (P&lt;0.05), respectively. A subset of animals lacking ovarian activity (n=81) and cyclic control females (n=24) underwent blood sample collection. Samples were analyzed for concentrations of red blood cells, hemoglobin, total protein, copper, glucose, calcium, iron, and phosphorus. Blood concentrations of glucose were higher and blood concentrations of copper were lower in females with inactive ovaries compared with cyclic females. After exclusion of animals with poor general health, the remaining females that did not have ovarian activity (n=234) were divided into one of three treatment groups: Group 1 (n=71) received a single treatment of subcutaneous copper and intramuscular multivitamins, plus daily intravenous infusion of phosphorous for 5 days and oral minerals and vitamins daily for 7 days; Group 2 (n=104) received a single intramuscular injection of 1500 IU of equine chorionic gonadotropin; Group 3 (n=64) were treated identically to group 1 females with the exception of receiving a single intramuscular injection of 1500 IU of equine chorionic gonadotropin at the end of the 7-day treatment period; A number of 20 females was a subset of Group 3 females who failed to respond to treatment – they were treated for 10 days with an intravaginal device containing progesterone followed by a single intramuscular injection of 1500 IU of equine chorionic gonadotropin given at intravaginal device removal. Group 3 females exhibited a higher ovarian response to treatment than either Group 2 or Group 1 females which were different from one another. Conception rate was lower in Group 2 females than in Group 1 and group 3 females which were not different. Embryonic mortality was higher in Group 2 than in Group 1 and 3 females which were not different.

Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development

Structured approaches like the adverse outcome pathway (AOP) framework offer great potential for depicting complex toxicological processes in a manner that can facilitate informed integration of mechanistic information in regulatory decisions. While this concept provides a structure for organizing evidence and facilitates consistency in evidence integration; the process, inputs, and manner in which AOPs and AOP networks are developed is still evolving. Following the OECD guiding principles of AOP development, we propose three AOPs for male reproductive tract abnormalities and derive a putative AOP network. The AOPs were developed using a fundamental understanding of the developmental biology of the organs of interest, paying close attention to the gestational timing of key events (KEs) to very specifically inform the domain of life stage applicability for the key event relationships (KERs). Chemical stressor data primarily from studies on low molecular weight phthalates (LMWPs) served to ‘bound’ the pathways of focus in this dynamic period of development and were integrated with the developmental biology data through an iterative process to define KEs and conclude on the extent of evidence in support of the KERs. The AOPs developed describe the linkage between 1) a decrease in Insl3 gene expression and cryptorchidism, 2) the sustained expression of Coup-tfII and hypospadias and 3) the sustained expression of Coup-tfII and altered Wolffian duct development/ epididymal agenesis. A putative AOP network linking AOP2 and AOP3 through decreased steroidogenic biosynthetic protein expression and converging of all AOPS at the population level impaired fertility adverse outcome is proposed. The network depiction specifies and displays the KEs aligned with their occurrence in gestational time. The pathways and network described herein are intended to catalyze collaborative initiatives for expansion into a larger network to enable effective data collection and inform alternative approaches for identifying stressors impacting this sensitive period of male reproductive tract development.

Efficiency of pre-pregnancy health check for eugenics on prevention and control of birth defects in Guangdong province

Objective To evaluate the effect of pre-pregnancy health check for eugenics on prevention and control of adverse pregnancy outcome including birth defects in Guangdong province. Methods Surveillance data on 1 953 746 childbearing couples participating in the pre-pregnancy health checkup for eugenics in various regions of Guangdong province from 2014 through 2017 were collected for a retrospective analysis. Results Of all the participants surveyed during the period, 37.36% were assessed with risk factors for having abnormal fetuses. The top five identified risk factors for birth defect among the childbearing women included not taking supplemental folic acid during early pregnancy (40.28%), common reproductive tract infection (17.26%), abnormality in urine test (16.61%), abnormality of reproductive tract (14.12%), and at elder age (10.29%); while, the top three risk factors for the men at childbearing age were at elder age (17.11%), abnormality in physical examination (10.95%), and abnormality in reproductive system (9.45%). A total of 779 722 childbearing women were followed-up to their deliveries or pregnancy terminations. The incidence of total adverse pregnancy outcome was 7.10%, and the incidence of total birth defects was 15.69 per 10 000 perinatal infants. Conclusion Pre-pregnancy health checkup for eugenics has significant effects on prevention and control of adverse pregnancy outcomes such as birth defects and the checkup should be carried out among childbearing couples continuously to reduce the incidence of birth defects.

Gestational vinclozolin exposure suppresses fetal testis development in rats

Vinclozolin is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor and is thought to be related to abnormalities of the reproductive tract. However, its mechanism of inducing abnormalities of the male reproductive tract is still unclear. The purpose of this study was to study the effect of gestational vinclozolin exposure on the development of rat fetal Leydig cells. Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by gavage from gestational day 14–21. Vinclozolin dose-dependently reduced serum testosterone levels at doses of 50 and 100 mg/kg and the anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blotting showed that vinclozolin down-regulated the expression of Nr5a1, Sox9, Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3, Amh, Pdgfa, and Dhh and their encoded proteins. Vinclozolin reduced the number of NR2F2-positive stem Leydig cells at a dose of 100 mg/kg and enhanced autophagy in the testes. In conclusion, vinclozolin disrupts reproductive tract development and testis development in male fetal rats via several pathways.

Developmental Exposure to Tetrabromobisphenol A Has Minimal Impact on Male Rat Reproductive Health

The flame retardant and plasticizer, tetrabromobisphenol-A (TBBPA) has rapidly become a common component in the manufacture of circuit boards and plastics worldwide. It is also an analog of bisphenol A (BPA), an endocrine disrupting chemical identified by the Endocrine Society. As such, TBBPA needs to be investigated for similar potential human health risks. Using rats as a model, we exposed pregnant dams and their progeny to 0, 0.1, 25, or 250 mg TBBPA/kg of body weight until the offspring reached adulthood and assessed the first generation of males for any reproductive tract abnormalities. We found no differences in the morphology of testes, sperm, prostates, or secondary sex organs from post-natal day 21 through one-year of age. A delay in the time to preputial separation was found with the 250 mg/kg treatment. Also, minor differences of sperm count at one-year old with the 25 mg/kg treatment and expression levels of two steroidogenic pathway enzymes at either post-natal day 90 or one-year old in the 250 mg/kg treatment group were detected, but spermatogenesis was not disrupted. While these results may lead to the supposition that TBBPA is less harmful than its parent compound BPA, more studies need to be conducted to assess long-term exposure effects.

Pathological and bacteriological studies on reproductive tract abnormalities of she-camels (Camelus dromedarius), emphasizing on zoonotic importance.

Objective:Infertility caused by reproductive pathologies plays a significant role in animal breeding and could result in massive economic losses to livestock owners. Hence, this study was designed to allocate various pathological lesions in the female reproductive tract of she-camels (Camelus dromedarius) slaughtered in Egypt and isolate the causative agents associated with those pathologies.Materials and Methods:A total of 500 genitalia of adult nonpregnant she-camels aged between 6 and 15 years old were collected from three slaughterhouses at the Giza Governorate, Egypt, from August 2017 to August 2019. The uterus, cervix, and vagina were examined pathologically and microbiologically.Results:The uteri of 152 cases (30.4%), cervices of 24 cases (4.8%), and vaginae of 20 cases (4.2%) showed pathological abnormalities. The uterine inflammatory lesions were detected in 119 cases (23.8%), and the non-inflammatory lesions were detected in 58 cases (11.6%). Pathological changes of the cervix comprised 4.8%, whereas vaginal abnormalities represented 4%. The total microbial recovery rate was 28.4%, and the isolated organisms included Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa, in addition to Candida albicans. Trials to isolate Brucella and Salmonella species were negative; however, virological examination revealed the isolation of bovine herpesvirus type-1 in two cases.Conclusion:Inflammatory lesions were the most prevailing pathological lesions observed along the genital tract of she-camels, and E. coli was the most prevalent isolate. The microbiological burden from the genital discharge could be of zoonotic importance to the examiner and could be a contaminant to the environment and, consequently, human. In addition, attention should be paid toward the possibility of infected she-camels to transmit such infections to farm animals in contact.