Nitric oxide in female reproductive system

Nitric oxide (NO), synthesized from L-arginine and oxygen by a family of enzymes known as nitric oxide synthase (NOS), is an effective and intercellular signal transduction molecule, and is ubiquitously present in vertebrates. To date, there are three distinct isoforms of NOS: neural NOS (nNOS), inducible NOS (iNOS), and endo-thelial NOS (eNOS). Among them, eNOS and nNOS, also called constitutive isoforms (cNOS), require calcium for activity, and are expressed constitutively in the physiological condition. The third isoforms, iNOS, whose activity is not dependent on calcium, are produced only in response to some stimulus, including cytokines and immune stimulating factors, etc.

Angiogenesis in female reproductive system

Neovascularization, i.e. new blood vessels formation, can be divided into two different processes: vasculogene-sis, whereby a primitive vascular network is established during embryogenesis from multipotential mesenchymal progenitors; and angiogenesis, which refers to the new blood vessels formation from pre-existing vessels[1,2].Angiogenesis contributes to the most process throughout the whole life span from embryonic development to adult growth’21. In this meaning, neovascularization is usually used to imply angiogenesis. Under physiological conditions, angiogenesis is a strictly regulated event and rarely happens in most adult tissues except for fracture or healing of wounds[2,3]. However, a notable phenomenon is that the tissues of ovary and uterine endometnum are unique in the cycle-specific changes in vascularity that occur in each estrous/menstrual cycle. Active angiogenesis occurs in placenta to satisfy the needs of embryonic implantation and development. Defects in angiogenesis are associated

Testing Potential Effect of Environmental Endocrine Disruptors in Cow Milk on Reproductive Index in Female Rats

To study the effect of endocrine disruptor chemicals in cow milk on female reproductive system. Methods A two-generation reproduction was conducted according to U. S. FDA standard. Milk was fed in special bottle to Wistar rats of both sexes through two successive generations （F0 and F1） in the milk group while artificial milk was fed to rats in the control group. Twenty-four rats of each sex were mated in each group. Measurements were made according to this guideline. Results Reproductive parameters in the milk group such as fertility index, gestation index, weights of uterus and ovary, days of vaginal opening, estrous cycles, histological morphological changes were comparable to those in the control group. However, the means of body weight had some differences. The body weight gains increased significantly in the milk-treated group in F1 and F2 generation compared with those in the control group. The concentration of insulin-like growth factor-1 （IGF-1） in blood in the milk group was comparable to that in the control group, but the standard deviation changed greatly in the milk-treated rats. Conclusion Endocrine disruptor chemicals in milk have no severe effects on the female reproductive system.

Evaluation of the Effects of Cypermethrin on Female Reproductive Function by Using Rabbit Model and of the Protective Role of Chinese Propolis

The prophylactic effects of Chinese propolis against cypermethrin toxicity were evaluated by performing ovary and uterus histopathology, as well as by characterizing ovarian function, embryos, and litters. Cypermethrin induced atypia in the ovary and uterus, and decreased the ovulation sites and the number of embryos. Cypermethrin-induced oxidative stress during pregnancy, decreased the parturition rate as well as the number and weight of offspring and increased the incidence of morphological malformations in the offspring. Administration of propolis to cypermethrin-treated animals mitigated cypermethrin-induced reproductive toxicity.

Protective effects of female reproductive factors on gastric signetring cell carcinoma

BACKGROUND The overall incidence of gastric cancer is higher in men than women worldwide.However,gastric signet-ring cell carcinoma(GSRC)is more frequently observed in younger female patients.AIM To analyze clinicopathological differences between sexes in GSRC,because of the limited evidence regarding association between sex-specific differences and survival.METHODS We reviewed medical records for 1431 patients who received treatment for GSRC at the Cancer Hospital,Chinese Academy of Medical Sciences between January 2011 and December 2018 and surveyed reproductive factors.Clinicopathological characteristics were compared between female and male patients.Cox multivariable model was used to compare the mortality risks of GSRC among men,menstrual women,and menopausal women.RESULTS Of 1431 patients,935 patients were male and 496 were female(181 menstrual and 315 menopausal).The 5-year overall survival in male,menstrual female and menopausal female groups was 65.6%,76.5% and 65%,respectively(P<0.01).Menstruation was found to be a protective factor(hazard ratio=0.58,95% confidence interval:0.42–0.82).CONCLUSION The mortality risk of GSRC in menstrual women was lower than that in men.This study identified the protective effects of female reproductive factors in GSRC.

Characteristics of management of reproductive endocrine problems in female patients

In 1956, my former Head and Professor of the Department of Obstetrics and Gynecology KT LIM, asked me to take the initiative to establish a reproductive endocrinology unit. As China is a developing country, we were then short of diagnostic facilities and therapeutic agents. We can learn basic knowledge and clinical experiences from the literature, but hormonal preparations were expensive and generally most of our patients were poor. We needed to find simpler, inexpensive and yet effective ways to treat our patients. In a word, we had to develop our own way.……

Association of novel and legacy PFAS with reproductive hormones in women of child‑bearing age

Objective:To evaluate the legacy and novel per-and polyfluoroalkyl substances(PFAS)exposure in women of reproductive age,and to explore the effects on female reproductive hormones.Methods:We used cross-sectional data of 433 normal women of reproductive age from 2013 to 2015.Data of age,age at menarche,parity,BMI,education,and income were collected through questionnaires,serum samples were collected for reproductive hormones,and plasma samples for PFAS measurement by ultraperformance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS).Multiple linear regression and quantile g-computation were adopted to analyze the association between PFAS and reproductive hormones.Results:The detection rates of 6:2 Cl-PFESA,8:2 Cl-PFESA and HFPO-DA in the plasma were 100%,99.8%and 99.9%,respectively.The median concentrations of these chemicals were 2.27 ng/mL,0.07 ng/mL and 0.03 ng/mL,respectively.Multiple linear regression analysis showed a positive association between branched PFOS[1m-PFOS(β=0.131,95%CI:0.021,0.242),br-PFOS(β=0.119,95%CI:0.005,0.234)]and progesterone.In addition,mixed exposure model suggested that PFAS had a positive association with progesterone(β=0.549,95%CI:0.323,0.774).Conclusion:In this study,a mixed exposure model was used to evaluate the combined effects of PFAS mixtures,reflecting the association between multiple environmental PFAS exposure and reproductive hormones,and a higher concentration of novel PFAS was found in women of reproductive age,confirming that PFAS exposure may be related to reproductive hormone disorders in women of reproductive age.

Maternal Thermal Effects on Female Reproduction and Hatchling Phenotype in the Chinese Skink(Plestiodon chinensis)

We maintained gravid Chinese skinks(Plestiodon chinensis) at three constant temperatures(25, 28 and 31 °C) during gestation, and randomly assigned eggs from each female to one of the same three temperatures for incubation to determine maternal thermal effects on female reproduction and hatchling phenotype. Maternal temperature affected egg-laying date, hatching success and hatchling linear size(snout-vent length, SVL) but not clutch size, egg size, egg component, and embryonic stage at laying. More specifically, females at higher temperatures laid eggs earlier than did those at low temperatures, eggs laid at 31 °C were less likely to hatch than those laid at 25 °C or 28 °C, and hatchlings from eggs laid at 31 °C were smaller in SVL. Our finding that maternal temperature(pre-ovipositional thermal condition) rather than incubation temperature(post-ovipositional thermal condition) affected hatching success indicated that embryos at early stages were more vulnerable to temperature than those at late stages. Our data provide an inference that moderate maternal temperatures enhance reproductive fitness in P. chinensis.

Bioengineering models of female reproduction

The female reproductive system consists of the ovaries,the female gonads,and the reproductive tract organs of the fallopian tubes,uterus,cervix,and vagina.It functions to provide hormonal support and anatomical structure for the production of new offspring.A number of endogenous and exogenous factors can impact female reproductive health and fertility,including genetic vulnerability,medications,environmental exposures,age,nutrition,and diseases.To date,due to the ethical concerns of using human subjects in biomedical research,the majority of studies use in vivo animal models and 2D cell/tissue culture models to study female reproduction.However,the complexity and species difference of the female reproductive system in humans make it difficult to compare to those of animals.Moreover,the monolayered cells cultured on flat plastics or glass lose their 3D architecture as well as the physical and/or biochemical contacts with other cells in vivo.Further,all reproductive organs do not work alone but interconnect with each other and also with non-reproductive organs to support female reproductive,endocrine,and systemic health.These facts suggest that there is an urgent and unmet need to develop representative,effective,and efficient in vitro models for studying human female reproduction.The prodigious advancements of bioengineering(e.g.,biomaterials,3D printing,and organ-on-a-chip)allow us to study female reproduction in an entirely new way.Here,we review recent advances that use bioengineering methods to study female reproduction,including the bioengineering models of the ovary,fallopian tube,uterus,embryo implantation,placenta,and reproductive disease.

Reproductive performance and gestational effort in relation to dietary fatty acids in guinea pigs

Background： Dietary saturated（SFAs） and polyunsaturated（PUFAs） fatty acids can highly affect reproductive functions by providing additional energy, modulating the biochemical properties of tissues, and hormone secretions. In precocial mammals such as domestic guinea pigs the offspring is born highly developed. Gestation might be the most critical reproductive period in this species and dietary fatty acids may profoundly influence the gestational effort. We therefore determined the hormonal status at conception, the reproductive success, and body mass changes during gestation in guinea pigs maintained on diets high in PUFAs or SFAs, or a control diet.Results： The diets significantly affected the females＇ plasma fatty acid status at conception, while cortisol and estrogen levels did not differ among groups. SFA females exhibited a significantly lower body mass and litter size, while the individual birth mass of pups did not differ among groups and a general higher pup mortality rate in larger litters was diminished by PUFAs and SFAs. The gestational effort, determined by a mother＇s body mass gain during gestation, increased with total litter mass, whereas this increase was lowest in SFA and highest in PUFA individuals. The mother＇s body mass after parturition did not differ among groups and was positively affected by the total litter mass in PUFA females.Conclusions： While SFAs reduce the litter size, but also the gestational effort as a consequence, PUFA supplementation may contribute to an adjustment of energy accumulations to the total litter mass, which may both favor a mother＇s body condition at parturition and perhaps increase the offspring survival at birth.

Fidgetin knockdown and knockout influences female reproduction distinctly in mice

Microtubule-severing proteins(MTSPs),are a family of proteins which use adenosine triphosphate to sever microtubules.MTSPs have been shown to play an important role in multiple microtubule-involved cellular processes.One member of this family,fidgetin(FIGN),is also involved in male fertility;however,no studies have explored its roles in female fertility.In this study,we found mouse fidgetin is rich within oocyte zona pellucida(ZP)and is the only MTSP member to do so.Fidgetin also appears to interact with all three ZP proteins.These findings prompted us to propose that fidgetin might prevent polyspermy.Results from in vitro maturation oocytes analysis showed that fidgetin knockdown did cause polyspermy.We then deleted all three fidgetin isoforms with CRISPR/Cas9 technologies;however,female mice remained healthy and with normal fertility.Of all mouse MTSPs,only the mRNA level of fidgetin-like 1(FIGNL1)significantly increased.Therefore,we assert that fidgetin-like 1 compensates fidgetin's roles in fidgetin knockout female mice.

Influence of Isoflurane Exposure for 15 Consecutive Days on Ovarian Function in Adult Female Mice

Female infertility after occupational exposure to inhaled anesthetic agents has attracted critical attention,but systematic studies focusing on the impact of inhaled anesthetics on the female reproductive system have not been well-established.We used a murine model to study the effect of isoflurane exposure on infertility in female adult mice and investigated the potential underlying mechanism.One hundred adult female C57 mice were randomly allocated into 5 groups exposed in air containing 0,2500,5000,10000 or 20000 ppm isoflurane for 15 consecutive days.Estrous cycle length was measured based on vaginal smear examination,ovarian histopathologic enumeration of follicles,and serum estradiol(E2),anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)levels to assess the effect of isoflurane on ovarian reserve.Compared to the control group,significant prolongation of the estrous cycle of the adult female mice was observed in the 20000 ppm isoflurane exposure group.Serum AMH was significantly decreased,and FSH and LH levels profoundly increased in the 5000,10000,and 20000 ppm isoflurane exposure groups compared to the control group.The histopathologic examination revealed a reduced number of developing follicles and an increased number of atretic follicles after isoflurane exposure,but the difference was not statistically significant.Thus,exposure to a higher concentration of isoflurane might have an adverse effect on ovarian reserve in sexually-mature female mice.

Body Size and Reproductive Tactics in Varanid lizards

Body size and female reproduction in the water adult females larger than 500 mm SVL and 32 adult males Ledong, Hainan under permit to our laboratory in Hainan monitor lizard （Varanus salvator） were studied. Forty-two larger than 400 mm SVL were donated by local people in in 2013 and 2014. The largest male and female measured 745 and 755 mm SVL, respectively. The mean SVL was greater in adult females than in adult males. Males had larger heads （head width） than females of the same SVL. The smallest reproductive female in our sample was 565 mm SVL. Females produced a single clutch of 17.1 （10-23） pliable-shelled eggs per breeding season stretching from mid-June and mid-September. Clutch size and clutch mass were all positively related to female SVL. However, there was no significant linear relationship between egg mass and female SVL. Larger females generally produced more eggs, and thus heavier clutches than did smaller ones. There was no significant linear relationship between relative clutch mass and female SVL. Phylogenetic generalized least squares （PGLS） analysis, accounting for phylogenetic relationships, showed that clutch size was positively correlated with mean maternal SVL in varanid lizards. PGLS analysis showed that phylogenetic relationships did not affect clutch （or/and egg） mass and the SVL although there were significant linear relationship between clutch （or/and egg） mass and mean maternal SVL. Therefore, we could draw some general conclusions about the body size and reproductive tactics in varanid lizards that larger females generally produced more eggs, larger eggs and thus heavier clutches than did smaller ones.

Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

The male and female reproductive tracts are complex microenvironments that have diverse functional demands. The immune system in the reproductive tract has the demanding task of providing a protective environment for a fetal allograft while simultaneously conferring protection against potential pathogens. As such, it has evolved a unique set of adaptations, primarily under the influence of sex hormones, which make it distinct from other mucosal sites. Here, we discuss the various components of the immune system that are present in both the male and female reproductive tracts, including innate soluble factors and cells and humoral and cell-mediated adaptive immunity under homeostatic conditions. We review the evidence showing unique phenotypic and functional characteristics of immune cells and responses in the male and female reproductive tracts that exhibit compartmentalization from systemic immunity and discuss how these features are influenced by sex hormones. We also examine the interactions among the reproductive tract, sex hormones and immune responses following HIV-1 infection. An improved understanding of the unique characteristics of the male and female reproductive tracts will provide insights into improving clinical treatments of the immunological causes of infertility and the design of prophylactic interventions for the prevention of sexually transmitted infections.

DEVELOPMENT OF FEMALE REPRODUCTIVE ENDOCRINOLOGY IN CHINA

Female reproductive endocrinology plays an important role in obstetrics and gynecology, and is a component part of perinatology, family planning and geriatrics. It is closely linked with the physiological changes, disease conditions and health care in different reproductive stages of a woman’s life. Ovarian function consists of ovulation and hormonal secretion, which acts upon the uterine endometrium and other target organs and feeds back to the hypothalamus-pituitary unit. Thus, it is connected with other endocrine systems, cerebral cortex and the external environment. Whether the ovrian function is normal or not reflects itself clinically in the changes of menstrual cycle and reproductive status and may be evaluated by laboratory assays.

Association of Body Mass Index with Hypothalamus-Pituitary-Ovarian Axis Hormones in Infertile Women in the Niger Delta Region, Nigeria

Background: Infertility is well-known global health problem that has significant impacts on an individual, families and communities. Many modifiable lifestyle risk factors increase the risk of women to several reproductive disorders. Aim: This study established the relationship between obesity and Hypothalamic-Pituitary-Ovarian (HPO) axis hormones in infertile women in the Niger Delta Region, Nigeria. Methodology: Six hundred and twenty-six (626) women aged 18 - 40 years comprising of 513 obese infertile women and 113 non obese women who served as control were recruited for the study. Anthropometric measurements were taken and Body Mass Index was calculated. A non-fasting venous blood sample was collected from the women and analyzed for serum Estrogen, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Progesterone, Inhibin B, and Prolactin using Enzyme linked immunosorbent assay method. Results: In the present study, the Body Mass Index of women with primary (1°) infertility is significantly (p < 0.05) higher than secondary (2°) infertility women. Whereas, women with 2° infertility were older and have a higher height than women with 1° infertility. The result revealed that serum estrogen, luteinizing hormone, follicle stimulating hormone and prolactin levels were significantly (p < 0.05) higher in the obese infertile women, while inhibin B and progesterone levels were significantly (p < 0.05) reduced in the obese infertile women compared to the control subjects. However, women with 1° infertility have a significantly higher LH and FSH levels than the 2° infertility women. Furthermore, the study revealed that hyperestrogenism is the most prevalent gonadal disorder in women with primary infertility and secondary infertility. The BMI of infertile women suffering Hyperestrogenism is significantly higher than any other female gonadal disorder. The result also showed that there is statistically significant positive correlation between BMI and Hypogonadism, Hypogonadotropic and Amenorrhoea in obese infertility women. While, no significant correlation between BMI and Hypergonadism and Hypergonadotropic was observed. Furthermore, there was a positive correlation between BMI and Hypothalamus-Pituitary Ovarian hormones, as BMI showed a positive correlation with LH, FSH, Estrogen, progesterone, and prolactin in women with primary and secondary infertility, while Inhibin B showed a negative correlation with BMI. Conclusion: There is a relationship between BMI and Hypothalamus-Pituitary Ovarian hormones, signifying that obesity could affect female reproduction and directly impact ovarian function. Therefore, body weight maintenance should be considered as a first line of management of Hypothalamus-Pituitary Ovarian hormonal related infertility.

Effects of Mycoestrogens on Female Reproduction

Zearalenone(ZEA)is produced by Fusarium species and a common contaminant in food.ZEA and its metabolites,α-andβ-zearalenol,α-andβ-zearalanol,and zearalanone,are mycoestrogens that can interfere with estrogen signaling.High levels of mycoestrogens reduced female fertility in farm animals and rodents,in which adverse effects of mycoestrogens on major events in female reproduction,including ovarian folliculogenesis,ovulation,ovarian steroidogenesis,fertilization,preimplantation embryo development and transport,embryo implantation,placentation,parturition,and lactation,have been reported in different experimental settings.Here,we review the in vivo effects of mycoestrogens on the main events in female reproduction.

Microbiome in Female Reproductive Health:Implications for Fertility and Assisted Reproductive Technologies

The microbiome plays a critical role in the process of conception and the outcomes of pregnancy.Disruptions in microbiome homeostasis in women of reproductive age can lead to various pregnancy complications,which significantly impact maternal and fetal health.Recent studies have associated the microbiome in the female reproductive tract(FRT)with assisted reproductive technology(ART)outcomes,and restoring microbiome balance has been shown to improve fertility in infertile couples.This review provides an overview of the role of the microbiome in female reproductive health,including its implications for pregnancy outcomes and ARTs.Additionally,recent advances in the use of microbial biomarkers as indicators of pregnancy disorders are summarized.A comprehensive understanding of the characteristics of the microbiome before and during pregnancy and its impact on reproductive health will greatly promote maternal and fetal health.Such knowledge can also contribute to the development of ARTs and microbiome-based interventions.

Importance of sperm morphology during sperm transport and fertilization in mammals

After natural or artificial insemination, the spermatozoon starts a journey from the site of deposition to the place of fertilization. However, only a small subset of the spermatozoa deposited achieves their goal： to reach and fertilize the egg. Factors involved in controlling sperm transport and fertilization include the female reproductive tract environment, cell-cell interactions, gene expression, and phenotypic sperm traits. Some of the significant determinants of fertilization are known （i.e., motility or DNA status）, but many sperm traits are still indecipherable. One example is the influence of sperm dimensions and shape upon transport within the female genital tract towards the oocyte. Biophysical associations between sperm size and motility may influence the progression of spermatozoa through the female reproductive tract, but uncertainties remain concerning how sperm morphology influences the fertilization process, and whether only the sperm dimensions per se are involved. Moreover, such explanations do not allow the possibility that the female tract is capable of distinguishing fertile spermatozoa on the basis of their morphology, as seems to be the case with biochemical, molecular, and genetic properties. This review focuses on the influence of sperm size and shape in evolution and their putative role in sperm transport and selection within the uterus and the ability to fertilize the oocyte.

Interspecific pollen transfer between two coflowering species was minimized by bumblebee fidelity and differential pollen placement on the bumblebee body

Aims When sympatric flowering plant species in a natural community share pollinators,study of plant-plant interactions via interspecific pollen transfer(iPT)is essential for understanding species coexistence.However,little is known about the extent of iPT between interactive species and its causes.Methods To explore how sympatric flowering plants sharing pollinators mini-mize deleterious effects of iPT,we investigated the pollination ecol-ogy of two endemic species,Salvia przewalskii and Delphinium yuanum,in an alpine meadow in the Hengduan mountains,southwest China.We quantified conspecific and interspecific visits by shared bumblebee pollinators,amounts of pollen placed on different body sites of the pollinators and stigmatic pollen loads on open-pollinated flowers.To examine whether iPT affects female fitness,we measured pollen germination and seed production in the two species in an artificial pollination experiment.Important Findingsone bumblebee species,Bombus trifasciatus,was found to be the sole effective pollinator for the two coflowering species.Pollination experiments indicated that deposition of heterospecific pollen could significantly decrease seed set in both species.Experiments showed that S.przewalskii pollen could germinate well on stigmas of D.yuanum,inhibiting conspecific pollen germination in D.yuanum.However,seed set was not lower under open pollination than under cross-pollination within species,suggesting that no female fitness loss was caused by iPT.in foraging bouts with pollinator switches,switches from S.przewalskii to D.yuanum were relatively more fre-quent(8.27%)than the converse(1.72%).However,iPT from S.prze-walskii to D.yuanum accounted for only 1.82%of total stigmatic pollen loads while the reverse iPT to S.przewalskii was 8.70%,indi-cating that more switches of bumblebees to D.yuanum did not result in higher iPT.by contrast,selection for reduced iPT to S.przewalskii would limit pollinator switches from D.yuanum.We found that a bumblebee generally carried pollen grains from both species but the two species differed in the position of pollen placement on the bum-blebee’s body;S.przewalskii’s pollen was concentrated on the dorsal thorax while D.yuanum’s pollen was concentrated ventrally on the head.This differential pollen placement along with pollinator fidelity largely reduced iPT between the two species with a shared pollinator.