Reproduction & Fertility最新文献

Abstract: Giant pandas are mono-estrus seasonal breeders, with the breeding season typically occurring in the spring. Successful fertilization is followed by an embryonic diapause, of variable length, with birth in the late summer/autumn. There is a need for additional understanding of giant panda reproductive physiology, and the development of enhanced biomarkers for impending proestrus and peak fertility. We aimed to determine the utility of non-invasive androgen measurements in the detection of both proestrus and estrus. Urine from 20 cycles (-40 days to +10 days from peak estrus) from 5 female giant pandas was analyzed for estrogen, progestogens and androgens (via testosterone and DHEA assays), and hormone concentrations were corrected against urinary specific gravity. Across proestrus, estrogens increased while progestogens and androgens decreased - at the point of entry into proestrus, androgens (as detected by the testosterone assay) decreased prior to progestogens and gave 4 days advanced warning of proestrus. At the time of peak estrus, androgens (as detected by the DHEA assay) were significantly increased at the time of the decrease in estrogen metabolites from the peak, acting as an alternative confirmatory indicator of the fertile window. This novel finding allows for enlargement of the preparative window for captive breeding and facilitates panda management within breeding programmes. Androgens allow an enhanced monitoring of giant panda estrus, not only advancing the warning of impending proestrus, but also prospectively identifying peak fertility.

Lay summary: Giant pandas have one chance at pregnancy per year. The 2-day fertile window timing varies by year and panda. This is monitored by measuring the level of estrogens in the urine, which increase, indicating an upcoming fertile period. After 1-2 weeks of increase, estrogens peak and fall, marking the optimal fertile time. We tested other hormones to see if we can predict the fertile window in advance, and the specific fertile time with more accuracy. In 20 breeding seasons from 5 females, we found androgens, usually thought of as male hormones, had an important role. Testosterone gives 4 days advanced warning of estrogens increasing. DHEA identified peak estrogen and the fertile time before needing to see a confirmed decrease in estrogen itself. Therefore, androgens help improve monitoring of the giant panda breeding season, giving early warning of fertility, key in facilitating captive breeding and giant panda conservation.

Abstract: Endometriosis is a common yet under-recognised chronic disease with one in nine (more than 830,000) women and those assigned female at birth diagnosed with endometriosis by the age of 44 years in Australia. In 2018, Australia was the first country to develop a roadmap and blueprint to tackle endometriosis in a nationwide, coordinated manner. This blueprint is outlined in the National Action Plan for Endometriosis (NAPE), created from a partnership between government, endometriosis experts and advocacy groups. The NAPE aims to improve patient outcomes in the areas of awareness and education, clinical management and care and research. As researchers and clinicians are working to improve the lives of those with endometriosis, we discuss our experiences since the launch of the plan to highlight areas of consideration by other countries when developing research priorities and clinical plans. Historically, major barriers for those with endometriosis have been twofold; first, obtaining a diagnosis and secondly, effective symptom management post-diagnosis. In recent years, there have been calls to move away from the historically accepted 'gold-standard' surgical diagnosis and single-provider specialist care. As there are currently no reliable biomarkers for endometriosis diagnosis, specialist endometriosis scans and MRI incorporating artificial intelligence offer a novel method of visualisation and promising affordable non-invasive diagnostic tool incorporating well-established technologies. The recognised challenges of ongoing pain and symptom management, a holistic interdisciplinary care approach and access to a chronic disease management plan, could lead to improved patient outcomes while reducing healthcare costs.

Lay summary: Endometriosis is a chronic disease where tissue like the lining of the uterus is found in other locations around the body. For the 830,000 people living with endometriosis in Australia, this often results in an immense burden on all aspects of daily life. In 2018, Australia was the first country to introduce a roadmap and blueprint to tackle endometriosis in a nationwide coordinated manner with the National Action Plan for Endometriosis. This plan was created as a partnership between government, endometriosis experts and advocacy groups. There are several other countries who are now considering similar plans to address the burden of endometriosis. As researchers and clinicians are working to improve the lives of those with endometriosis, we share our experiences and discuss areas that should be considered when developing these national plans, including diagnostic pathways without the need for surgery, and building new centres of expertise in Endometriosis and Pelvic Pain.

Endometriosis is a benign disease that can cause pain and infertility in women. Debate exists over how endometriosis should best be diagnosed. On one hand, endometriosis can be diagnosed by directly examining pelvic anatomy via a surgical procedure known as diagnostic laparoscopy. On the other hand, the disease can be diagnosed via non-surgical means such as using medical imaging, the symptoms described by the patient and whether the patient responds to non-surgical therapies such as medication. In this debate article, we argue in favour of diagnostic laparoscopy. We review the safety of the procedure, compare the ability of diagnostic laparoscopy vs medical imaging to detect endometriosis and consider the benefits of formally diagnosing or ruling out the condition.

Group B Streptococcus (GBS) is an opportunistic pathogenic bacterium which upon colonization in the female reproductive tract can cause preterm births, fetal injury, and demise. Several determinants for GBS pathogenesis have been explored so far through the studies using animal models ranging from mice to non-human primates. The results from these experimental data have identified outer membrane vesicles, β-hemolysin, hyaluronidase, and Cas9 of GBS as major virulence factors leading to preterm births. Most of these factors drive inflammation through activation of NLRP3 and elevated production of IL1-β. However, the absence of one of the factors from the pathogen reduces but does not completely abolish the pathogenesis of GBS suggesting the involvement of more than one factor in causing preterm birth. This makes further exploration of other virulence factors of GBS pathogenesis important in gaining an insight into the mechanistic basis of GBS-mediated preterm births.

Lay summary: Group B Streptococcus (GBS) is a pathogenic bacteria whose infection in the reproductive tract during pregnancy can cause premature delivery. This bacterial infection is one of the major causes of death of mother and baby during pregnancy, and the bacteria is prevalent in all parts of the world. This makes the research on GBS so important and many of the mechanisms behind GBS infection during pregnancy still remain unexplored. In this review, we have outlined how various animal models contributed in finding the mechanism of GBS pathogenesis. The review also focuses on compiling various virulence factors which makes GBS pathogenic in the vulnerable. Understanding the mechanisms of infection by GBS will be crucial in developing drugs and vaccines to protect against the harmful effects of the bacteria.

Ad libitum: feeding in broiler breeder (BB) hens causes reduced egg production, lower fertility, and improper eggshell deposition. Restricted feeding (RF) is the only effective intervention available to normalize ovarian function and improve reproductive efficiency. This study aimed to assess the transcriptional changes in ovarian cortex of BB hens with free access to feed compared to those on a RF diet. RNA was isolated from the ovarian cortex of Cobb 500 pullets raised to 10 and 16 weeks of age on either a full-feeding (FF) or RF diet. Microarray analysis identified 386 differentially expressed genes between the two feeding groups at 16 weeks of age. Gene ontology enrichment identified overrepresentation of Neuroactive ligand-receptor interaction pathways, Cell adhesion molecules, Steroid hormone biosynthesis, and various KEGG pathways. From these groups, 46 genes were selected for follow-up validation by quantitative PCR. The findings show that 33 of the 46 genes had significantly different abundance by age and/or feeding level. Most of these genes were repressed in RF hens and belonged to the steroid biosynthesis and neuropeptide signaling groups. The VIPR2 receptor was higher in the FF group leading us to hypothesize that vasoactive intestinal peptide (VIP) is an important regulator of small cortical follicles. Culture of hen cortical follicles with VIP increased Star, an indication of increased steroidogenic activity, although did not elevate Cyp11a1. These results offer insights and suggest the possible mechanisms and pathways responsible for the increases in cortical follicle growth associated with excess feed intake in BB hens.

Lay summary: Giving breeder hens unrestricted access to feed can lead to problems with their ovaries, including excessive growth of the ovary and reduced fertility. Giving a limited amount of feed is the only effective way to reduce this growth of the ovaries and improve fertility. This study aimed to assess the changes in the molecules that make proteins in the body in hens fed unrestricted and restricted diets. In the hens fed a limited amount of feed, there were more of one type of molecules, while there were more of another type in the ovaries of hens with unrestricted access to feed. These results show that how much a hen eats can alter the number of these molecules in the ovary and this could help us understand why their ovaries grow excessively and why their eggs are less fertile.

Endometriosis is the most prevalent benign gynaecologic disease with invalidating effects on the quality of life and decreased economic productivity. As pharmacologic and surgical treatment are only partially effective, women look for self-management strategies in order to control their symptoms. Many dietary interventions have been claimed successful. But it is unclear whether these effects are caused by the idea of taking control of the symptoms by adhering to a diet or by the dietary intervention itself. In order to gain more evidence with regard to the mechanisms behind the effect of dietary intervention in the management of endometriosis, a number of issues need to be addressed for future studies. First, we need clearly defined endpoints in our studies. Secondly, we have to be aware of the difference between the effects of diet on the risk of developing endometriosis and the effects of diet on symptoms in women with already established endometriosis. Thirdly, it may be difficult to strictly define the intervention diet and the control or placebo diet. Fourthly, we have to define endometriosis-related as well as patient-related factors that may influence the success of a dietary intervention. Fifthly, we have to understand the biological mechanisms behind the perceived effects of dietary interventions. These issues will be addressed in this opinion paper.

Lay summary: Endometriosis, defined as the presence of endometrium-like tissue located outside the womb, is a gynaecologic disease that affects many women. They experience severe pain, making it difficult for them to go to school or work. Medication or surgery is often not enough to relieve their pain. Therefore, these women look for ways to suppress their pain by changing their way of life. Changing their diet is an option that is often chosen by women with endometriosis. Many women experience that changing their diet helps to suppress pain symptoms. But it is not clear why changing the diet is effective. Processes in the body could be changed by taking or avoiding specific nutrients, but the effect could also be caused by the empowerment that women experience by adhering to a diet. If we want to learn more about the effect of diet on endometriosis, we have to pay attention to the following issues: first, it is important to exactly define the goal of a new study. Secondly, we have to realize that there is a difference between the study of the effect of diet on the risk of developing endometriosis and the effect of diet on endometriosis that has already developed. Thirdly, we have to realize that it can be difficult to define what the diet contains and how a control group should be defined. Fourthly, it is important to define factors that make it difficult to adhere to a diet. Fifthly, we need to try to understand what happens in the body that may cause the effect of a diet in endometriosis. In this opinion paper, these issues will be addressed.

Some human preimplantation embryos are chromosomally mosaic. For technical reasons, estimates of the overall frequency vary widely from <15 to >90% and the true frequency remains unknown. Aneuploid/diploid and aneuploid/aneuploid mosaics typically arise during early cleavage stages before the embryonic genome is fully activated and when cell cycle checkpoints are not operating normally. Other mosaics include chaotic aneuploid mosaics and mixoploids, some of which arise by abnormal chromosome segregation at the first cleavage division. Chimaeras are similar to mosaics, in having two genetically distinct cell populations, but they arise from more than one zygote and occur less often. After implantation, the frequency of mosaic embryos declines to about 2% and most are trisomic/diploid mosaics, with trisomic cells confined to the placenta. Thus, few babies are born with chromosomal mosaicism. This review discusses the origin of different types of chromosomal mosaics and chimaeras; their fate and the relationship between preimplantation chromosomal mosaicism and confined placental mosaicism in human conceptuses and animal models. Abnormal cells in mosaic embryos may be depleted by cell death, other types of cell selection or cell correction but the most severely affected mosaic embryos probably die. Trisomic cells could become restricted to placental lineages if cell selection or correction is less effective in placental lineages and/or they are preferentially allocated to a placental lineage. However, the relationship between preimplantation mosaicism and confined placental mosaicism may be complex because the specific chromosome(s) involved will influence whether chromosomally abnormal cells survive predominately in the placental trophoblast and/or placental mesenchyme.

Lay summary: Human cells normally have 23 pairs of chromosomes, which carry the genes. During the first few days of development, some human embryos are chromosomal mosaics. These mosaic embryos have both normal cells and cells with an abnormal number of chromosomes, which arise from the same fertilised egg. (More rarely, the different cell populations arise from more than one fertilised egg and these embryos are called chimaeras.) If chromosomally abnormal cells survive to term, they could cause birth defects. However, few abnormal cells survive and those that do are usually confined to the placenta, where they are less likely to cause harm. It is not yet understood how this restriction occurs but the type of chromosomal abnormality influences which placental tissues are affected. This review discusses the origin of different types of chromosomally abnormal cells, their fate and how they might become confined to the placenta in humans and animal models.

Embryo transfer is the most emotional part for patients during in vitro fertilization treatment. Over the last decade, the embryo transfer procedure has undergone numerous changes in the guidelines in order to increase pregnancy rates. One such procedure is the loading of the embryo into the catheter, a thin tube that helps us transfer embryo into the uterine cavity. Very few research studies looked closely at embryo-loading technique per se. Furthermore, different infertility laboratories use various techniques to load embryo. The aim of our study was to compare the two most popular embryo-loading techniques. In 249 women, we transferred embryo aspirated into the catheter with small droplets of air, and in the group of 244 patients, we filled catheter only with fluid. Our main outcome measured was the clinical pregnancy rate. Based on our results, we did not find that embryo-loading technique affected patient's chances of achieving pregnancy.

A mouse model to study uterine specific contributions to pregnancy.Maternal environmental exposures can exert impacts on the ability of the uterus to sustain healthy pregnancy. To establish an in vivo model to study this, we designed an ovariectomized mouse embryo transfer model. The rationale being future studies could expose recipient female mice to variables such as altered diet, drug, temperature, air, or activity exposure among others to define their impacts on the uterine contribution to pregnancy. Ovariectomy ensures the extent of the variable is limited to exploring outcomes on uterine but not ovarian function. Embryo transfer from healthy, unexposed donor mice guarantees that any impacts of the variable are attributed to the maternal uterine but not the embryonic state. Pregnancy outcomes including pregnancy success (number of implantation sites) and viability (number of viable vs resorbing implantation sites) can be investigated. Numerous functional outcomes can be assessed, including developmental competence encompassing decidual, placental, fetal, and vascular morphology and/or function (e.g. measured using Doppler ultrasound, comparisons of fetal growth, or molecular or histological characterization of the decidua, placenta, and fetal tissues).

Lay summary: Many pregnancy complications occur because of problems in the womb (uterus), specifically the womb lining. There is a close relationship between the hormone function of the ovaries and the uterus and distinguishing between the way they both impact pregnancy success is difficult in existing studies using animals. Here, we developed a new animal model to utilize in addressing these gaps in our understanding of pregnancy.

Q fever is a bacterial disease that passes between animals and humans and causes disease in both. The disease has been associated with pregnancy complications including miscarriage. This study was undertaken to identify if Q fever exposure was correlated with miscarriage in 369 women attending a pregnancy support unit in Edinburgh. The women in the study were in two groups, the miscarriage group with 251 women who had experienced a miscarriage and a control group of 118 women who had not experienced miscarriage. Three women were found to be positive for Q fever antibodies, suggesting that they had previously been exposed to the infection and all of them were from the group who had experienced miscarriage. The study indicates that Q fever is relatively rare in women attending an urban Scottish hospital suggesting that the infection is not a major cause of miscarriage in this population. However, as Q fever antibodies could only be found in women within the miscarriage group, it suggests that the infection cannot be ruled out as a potential cause of miscarriage in individual cases.