Systems Biology in Reproductive Medicine最新文献

Sperm rheotaxis refers to the ability of sperm cells to align their swimming direction with or against fluid flow. Positive rheotaxis (PR) is the tendency of sperm cells to swim against the flow. Herein, we describe sperm rheotaxis in fertile and infertile males, using a microfluidic platform and focus on rheotaxis as a potential marker of male fertility. A previously reported computer-assisted sperm analysis (CASA) plugin for Image-J was used to detect and analyze the motion of human sperm cells in microfluidic environments. The fabricated microchannels mimic the female reproductive tracts and use an image-processing program to monitor sperm swimming behavior in semen samples from fertile and infertile men. We have constructed an image-processing pipeline. The image-processing pipeline incorporated strengthens object detection and particle tracking to adapt to sperm that are out of focus while swimming on the same track. PR% was defined as the number of PR sperm cells over the number of motile sperm cells. The results showed that the percentage of PR correlates with fertility, wherein the fertile male specimens showed a higher PR% than the other groups (P < 0.05). There is no difference in progressive motility between the control group (fertile men with normal sperm analysis) and group 1 (G1; infertile men with normal sperm analysis). However, PR% was lower (P < 0.05) in the G1 group (13.5 ± 0.4%) compared to the control group (40.3 ± 3.3%) and group 2 (G2; infertile with reduced sperm motility) (15.3 ± 4.6%). Thus, PR% may be used as a novel parameter to explain infertility even in situations where basic sperm analysis following the World Health Organization (WHO) guidelines is unable to do so. We propose to use PR% as a novel parameter for sperm analysis and as a method of sperm selection in assisted reproductive technology.

In this study, we aimed to evaluate whether post-thaw culture duration affected the clinical outcomes of frozen blastocyst transfer. This retrospective cohort study included 3,901 frozen-thawed blastocyst transfer cycles. The cohorts were divided into two groups based on the developmental stage (day 5 [D5] and day 6 [D6]) and culture duration after thawing (short culture, 2-6 h; long culture, 18-20 h). Women in the short culture group following D6 blastocyst transfer were further divided into three subgroups depending on the post-thaw culture period (2, 4, and 6 h). The main outcomes, namely live birth rate (LBR), implantation rate (IR), clinical pregnancy rate (CPR), and abortion rate (AR), showed no statistical differences within the groups following D5 blastocyst transfer. Patients in the long culture group had significantly lower IR (35.5 vs. 45.8%, p < 0.001), CPR (45.3 vs. 56.6%, p = 0.001), and LBR (35.5 vs. 48.5%, p < 0.001) but a significantly higher AR (21.6 vs. 14.3%, p = 0.049) following D6 blastocyst transfer than those in the short culture group. However, the data failed to present the superiority of any short culture duration over another on the live birth outcome for embryos vitrified on D6 (adjusted odds ratio [aOR]: 0.96, 95% confidence interval [95% CI]: 0.53-1.73, p = 0.881, for the 4-h vs. 2-h subgroup; aOR: 1.01, 95% CI: 0.68-1.49, p = 0.974, for the 6-h vs. 2-h subgroup). Both post-thaw protocols can be applied to patients with D5 blastocysts. To optimize the pregnancy outcomes following D6 blastocyst transfer, a short culture period is recommended. Any of the three short culture durations (2, 4, and 6 h) can be applied, depending on the workflow of the laboratory.

Increasing female age is accompanied by a corresponding fall in her fertility. This decline is influenced by a variety of factors over an individual's life course including background genetics, local environment and diet. Studying both coding and non-coding RNAs of the embryo could aid our understanding of the causes and/or effects of the physiological processes accompanying the decline including the differential expression of sub-cellular biomarkers indicative of various diseases. The current study is a post-hoc analysis of the expression of trophectoderm RNA data derived from a previous high throughput study. Its main aim is to determine the characteristics and potential functionalities that characterize long non-coding RNAs. As reported previously, a maternal age-related component is potentially implicated in implantation success. Trophectoderm samples representing the full range of maternal reproductive ages were considered in relation to embryonic implantation potential, trophectoderm transcriptome dynamics and reproductive maternal age. The long non-coding RNA (lncRNA) biomarkers identified here are consistent with the activities of embryo-endometrial crosstalk, developmental competency and implantation and share common characteristics with markers of neoplasia/cancer invasion. Corresponding genes for expressed lncRNAs were more active in the blastocysts of younger women are associated with metabolic pathways including cholesterol biosynthesis and steroidogenesis.

Hyperhomocysteinemia (HHcy) is an autosomal recessive inherited metabolic disease caused by variations in folate metabolism genes, characterized by impaired methionine metabolism and accumulation of homocysteine (Hcy) in the blood serum. It was shown that men usually have higher plasma Hcy levels than women, but have not yet assessed the leading factors of these differences, which is important for the development of personalized protocols for the prevention of folate metabolism disorders in couples with reproductive disorders. This study aimed to analyze the effect of intergenic and gene-factor interactions on the risk of developing HHcy in men and women of married couples with reproductive disorders. In our study were involved 206 married Caucasian couples (206 males and 206 females) from central regions of Ukraine with early pregnancy losses in the anamnesis. We found that the incidence of HHcy in men was significantly higher than in women. Gender differences in folic acid and vitamin B12 levels were identified. The best predictors of HHcy in men (MTRR (A66G), MTHFR (C677T), MTR (A2756G), vitamin B12 level) and in women (MTHFR (C677T), MTR (A2756G), vitamin B12 level) were selected by binary logistic regression. There was no significant difference in the distribution of genotypes by the studied gene variants when comparing men and women with HHcy. Our findings demonstrate that there is a gender difference in the development of HHcy. This difference is caused by intergenic interaction and by environmental factors, in particular, nutrition and vitamins consumption.

Despite the long-standing notion of "oxidative stress," as the main mediator of many diseases including male infertility induced by increased reactive oxygen species (ROS), recent evidence suggests that ROS levels are also increased by "reductive stress," due to over-accumulation of reductants. Damaging mechanisms, like guanidine oxidation followed by DNA fragmentation, could be observed following reductive stress. Excessive accumulation of the reductants may arise from excess dietary supplementation over driving the one-carbon cycle and transsulfuration pathway, overproduction of NADPH through the pentose phosphate pathway (PPP), elevated levels of GSH leading to impaired mitochondrial oxidation, or as a result NADH accumulation. In addition, lower availability of oxidized reductants like NAD⁺, oxidized glutathione (GSSG), and oxidized thioredoxins (Trx-S2) induce electron leakage leading to the formation of hydrogen peroxide (H₂O₂). In addition, a lower level of NAD⁺ impairs poly (ADP-ribose) polymerase (PARP)-regulated DNA repair essential for proper chromatin integrity of sperm. Because of the limited studies regarding the possible involvement of reductive stress, antioxidant therapy remains a central approach in the treatment of male infertility. This review put forward the concept of reductive stress and highlights the potential role played by reductive vs oxidative stress at pre-and post-testicular levels and considering dietary supplementation.

The application of nanotechnology in the present era has substantial impact on different industrial and medical fields. However, the advancement in nanotechnology for potential therapeutic and consumer benefits has been an anxious cause regarding the probable hazardous consequences of these molecules in biological systems and the environment. The toxic effects can perturb the physiologic system broadly and reproductive function and fertility specifically. Despite engineered nanomaterials (ENMs) having a wide range of applications, toxicological investigations of the probable ramifications of ENMs on the reproductive systems of mammals and fertility remains in its nascence. Complication in the male reproductive system is quite a pertinent issue in today's world which comprises of benign prostatic enlargement, prostate cancer, and unhealthy sperm production. The therapeutic drugs should not only be active in minimum dose but also site-specific in action, criteria being met by nanomedicines. Nanomedicine therapy is promising but encompasses the chances of adverse effects of being cytotoxic and generating oxidative stress. These hurdles can be overcome by creating coated nanoparticles with organic substances, modification of shape and size, and synthesizing biocompatible green nanoparticles. This review attempts to look into the applications of most widely used metals like zinc, titanium, silver, and gold nanoparticles in the therapy of the male reproductive system, their prospective harmful effects, and the way out to create a safe therapeutic system by specific modifications of these metal and metal oxide nanoparticles.

Women who are undergoing preimplantation genetic testing for aneuploidy (PGT-A) often wish to know how many eggs will be required to optimize the chances of a live birth. However, no precise data on this can yet be provided during genetic counseling for this procedure. On the basis of PGT-A data from related studies and current databases, we have estimated that the number of zygotes required for a 50% chance of a live birth is 8 at age 40 but increases markedly to 21 at age 43. PGT-A markedly reduces the miscarriage rate per embryo transfer but does not alleviate the extremely high number of zygotes required for a live birth in women of an advanced maternal age. Detailed genetic counseling will therefore be desirable prior to undergoing this procedure.

Maternal diabetes-mediated fetal programming is widely discussed, however, it is important to define the extent to which intrauterine hyperglycemia interferes with the health of female pups, along with determining whether these changes can be perpetuated across generations. This study aimed to evaluate the effects of maternal diabetes on fetal programming and the repercussions on the metabolism of pregnant and nonpregnant female pups. Diabetes status was induced (diabetic group-D) using streptozotocin (a beta cell cytotoxic drug) on the fifth postnatal day of female rats, while controls received a citrate buffer (Control-C). In adulthood, the rats were mated to obtain their female pups. At 90 days of age, half of the female pups were mated (preg) and the other half continued virgin (Npreg). Furthermore, they were distributed into four groups: OC/Npreg and OC/preg-female pups from control mothers; OD/Npreg and OD/preg-female pups from diabetic mothers. At 115 days of life and/or 17 days of pregnancy, the oral glucose tolerance test (OGTT) was performed with blood collection for insulin measurement. At 120 days of life and/or 21 days of pregnancy, the rats were anesthetized and euthanized to determine their blood oxidative stress status. The OD/Npreg group showed glucose intolerance during OGTT (p < 0.0001), while the OD/preg group showed increased insulin secretion during OGTT (p < 0.0001) and insulin resistance (IR; p = 0.0027). An increase in homeostatic model assessment β was shown in the pregnant groups, regardless of maternal diabetes (p < 0.0001). The OD/preg group presented increased thiobarbituric acid reactive substances (p < 0.0001) and -SH levels (p = 0.0005) and decreased superoxide dismutase activity (p = 0.0063). Additionally, small fetuses for gestational age (p < 0.0001) were found in these rats. In conclusion, exposure to maternal hyperglycemia compromises the glycemic metabolism of female pups before and during pregnancy and causes oxidative stress, IR, and impaired fetal growth during pregnancy.

Under normal conditions, to achieve optimal spermatogenesis, the temperature of the testes should be 2-6 °C lower than body temperature. Cryptorchidism is one of the common pathogenic factors of male infertility. The increase of testicular temperature in male cryptorchidism patients leads to the disorder of body regulation and balance, induces the oxidative stress response of germ cells, destroys the integrity of sperm DNA, yields morphologically abnormal sperm, and leads to excessive apoptosis of germ cells. These physiological changes in the body can reduce sperm fertility and lead to male infertility. This paper describes the factors causing testicular heat stress, including lifestyle and behavioral factors, occupational and environmental factors (external factors), and clinical factors caused by pathological conditions (internal factors). Studies have shown that wearing tight pants or an inappropriate posture when sitting for a long time in daily life, and an increase in ambient temperature caused by different seasons or in different areas, can cause an increase in testicular temperature, induces testicular oxidative stress response, and reduce male fertility. The occurrence of cryptorchidism causes pathological changes within the testis and sperm, such as increased germ cell apoptosis, DNA damage in sperm cells, changes in gene expression, increase in chromosome aneuploidy, and changes in Na⁺/K⁺-ATPase activity, etc. At the end of the article, we list some substances that can relieve oxidative stress in tissues, such as trigonelline, melatonin, R. apetalus, and angelica powder. These substances can protect testicular tissue and relieve the damage caused by excessive oxidative stress.