Ovary has a fix number of germ cells during fetal life in mammals. The germ cells are depleted rapidly and a large number of germ cells (≥99%) are eliminated from the cohort of ovary through follicular atresia during prepubertal life. The various cell death pathways including apoptosis, autophagy, necrosis, and necroptosis are involved in follicular atresia. Hence, <1% of germ cells are culminated into oocytes that are available for meiotic maturation and ovulation during entire reproductive life. These oocytes are arrested at diplotene stage of meiotic prophase-I and remain arrested for few months to several years during entire reproductive life. Resumption from diplotene arrest in follicular oocytes starts in response to gonadotropins surge and progresses through metaphase-I to metaphase-II stage that extrudes first polar body at the time of ovulation. Surprisingly, oocytes do not wait for fertilizing spermatozoa and quickly undergo abortive spontaneous oocyte activation (SOA) in few mammalian species including humans. The abortive SOA makes oocyte unfit for fertilization and limits assisted reproductive technologies outcome. Indeed, majority of germ cells and oocytes are eliminated from the cohort of ovary and only few oocyte that are of good quality get selectively recruited to become right gamete after ovulation during entire reproductive life span in mammals.
Ovary has a fix number of germ cells during fetal life in mammals. The germ cells are depleted rapidly and a large number of germ cells (≥99%) are eliminated from the cohort of ovary through follicular atresia during prepubertal life. The various cell death pathways including apoptosis, autophagy, necrosis, and necroptosis are involved in follicular atresia. Hence, <1% of germ cells are culminated into oocytes that are available for meiotic maturation and ovulation during entire reproductive life. These oocytes are arrested at diplotene stage of meiotic prophase-I and remain arrested for few months to several years during entire reproductive life. Resumption from diplotene arrest in follicular oocytes starts in response to gonadotropins surge and progresses through metaphase-I to metaphase-II stage that extrudes first polar body at the time of ovulation. Surprisingly, oocytes do not wait for fertilizing spermatozoa and quickly undergo abortive spontaneous oocyte activation (SOA) in few mammalian species including humans. The abortive SOA makes oocyte unfit for fertilization and limits assisted reproductive technologies outcome. Indeed, majority of germ cells and oocytes are eliminated from the cohort of ovary and only few oocyte that are of good quality get selectively recruited to become right gamete after ovulation during entire reproductive life span in mammals.
Female reproduction is a blend of neuroendocrine, endocrine, and autocrine/paracrine factors that maintain the appropriate ovarian micro-environment. The growing urbanization prompted exposure to a myriad of environmental toxins carrying the ability to interfere with reproductive processes governed by endogenous hormones, making reproductive health a major global concern. These environmental anthropogenic contaminants, popularly termed as endocrine-disrupting chemicals (EDCs), can disrupt the ovarian homeostasis leading to serious perturbations, namely, anovulation, infertility, estrogen deficiency, and premature ovarian failure. Although gonadotropin action, biosynthesis of gonadal steroids vis-à-vis growth factors comprise the essential modulators within the ovary, the redox balance along with inflammatory and cell death response can dramatically influence the framework of ovarian dynamics; however, details of which remain relatively less understood. The present overview provides an update on candidates (endocrines and autocrine/paracrine) of oogenesis, and the potential impact of EDCs on diverse intra-ovarian entities including but not limited to gonadotropin action, steroidogenic potential, expression of growth factors, and modulation of maturational competence. Moreover, the relative importance of free radical-induced stress, inflammation, and elevated cell death (follicular atresia), in the regulation of ovarian functions and how these intricate yet conjoined mechanisms may alter the reproductive performance of a female will be an issue of discussion.
Oocyte meiosis is a prolong series of events that are comprised several intermittent channels in mammals. Oocyte meiosis starts during fetal life and then gets arrested at diplotene stage of first meiotic prophase in follicular oocyte. The continuous transfer of cyclic adenosine 3’, 5’-monophosphate (cAMP) and cyclic guanosine 3’, 5’-monophosphate (cGMP) from encircling granulosa cells to the oocyte through gap junctions helps in the maintenance of their high level required to achieve the long-lasting diplotene arrest so-called germinal vesicle stage. Phosphodiesterase inhibitors have been used to elevate intracellular level of both cyclic nucleotides and prevent spontaneous resumption of meiosis in oocytes under in vitro culture conditions. On the other hand, disruption of gap junction either by pituitary gonadotropin or by physical removal of encircling granulosa cells interrupts transfer of these nucleotides to the oocyte. As a result, intraoocyte cAMP as well as cGMP levels are decreased drastically that initiate downstream pathways to destabilize maturation-promoting factor (MPF). The destabilized MPF initiates meiotic resumption from diplotene arrest in mammalian oocytes. Oocyte meiosis further progresses from metaphase I to metaphase II stage and extrudes first polar body to get converted into haploid female gamete at the time of ovulation. Indeed, high level of cAMP as well as cGMP levels maintains diplotene arrest for a long time in follicular oocytes. On the other hand, transient decrease of their levels drives resumption from diplotene arrest, thereby meiotic maturation process, which enables oocyte to achieve developmental competency. Any defect in this process directly affects oocyte quality and thereby reproductive outcome in mammals including human.
This review article has comprehensively covered the benefits of uterine ligation simultaneous laparoscopic myomectomy in the views of operative time, operative blood loss, hospital stay, recurrent rate and symptoms relief in recent articles. The information has been derived from medical database such as SprinkerLink, DOAJ, CINAHL, EBSCO delivery system, PubMed-NCBI, Sciencedirect, HighWire, Web of Science and ProQuest. There were only 3 articles which met my research criteria. The positive result of combined operation was reduction of operative blood loss for all studies. But 2 articles showed the operative time in combined operation more than single procedure. One study had a better percentage of symptom relief in a group of combined operation and tendency to decline in recurrent rate. However other articles revealed no difference in recurrent rate and pregnancy rate in both groups. Nowadays we still need more information from further randomized controlled trial studies to prove the hypothesis of benefits and risks of this add-on procedure.
The impact of elevated serum progesterone levels on pregnancy and live birth during in vitro fertilization (IVF) remains unclear. Our objective was to investigate whether elevated serum progesterone on the day of human chorionic gonadotropin (HCG) administration is associated with lower pregnancy and live birth rates. This mini review provides a synopsis of the literature in addition to some of our own data. On the whole pregnancy and live birth rates decrease with increasing progesterone on the day of HCG administration even after adjusting for confounders. The findings from the majority of manuscripts investigating this question appear to be in agreement.
A major goal of regenerative medicine is to devise strategies to restore structure and function of damaged or lost organs/tissues. Stem cell therapy has emerged as one of the most promising tools in regenerative medicine. The ability to self-renew and differentiate into multiple cell types positions stem cells as wonder drugs or cellular drugs of the future. Recent accomplishments in transforming terminally differentiated cells to stem cells by reprogramming have widened the scope of opportunities for regenerative medicine. On the other hand, stem cells are believed to have a causal role in the pathogenesis of some diseases such as cancers. These wide-ranging clinical implications have driven researchers to search different tissues and organs for the presence of stem cells and characterize them further for their differentiation potential. The endometrium or the inner lining of the uterus has also been explored for the presence of stem cells. Endometrial stem cells (ESCs) have gained importance, not only because of their multi-potent nature but also due to the ease of their availability through a natural event i.e. menstruation. The first evidence for the presence of stem cells in human endometrium arrived in 2004. Since then, ESCs displaying different molecular phenotypes have been identified in humans. ESCs have been shown to differentiate into the cells of different lineages. Further, ESCs have been investigated for their potential role in some uterine pathologies. This review provides a bird's eye-view of our current understanding pertaining to the role of stem cells in the pathogenesis of endometriosis.
For an over-burdened economy, such as India, reproductive health challenges are enormous to meet population demands. Successive governments through promotion of best policies and practices have reinforced this national priority, but failed to overcome pragmatic impediments even after sixty-eight years post-independence. The link between population dynamics and sustainable development has been jeopardized by a number of structural and social issues. Despite meeting several millennium development goal's target, major reproductive health concerns, such as need for contraception, unsafe abortion services, gender inequality, violence against women, and vulnerability to sexual transmitted diseases including HIV and cancers of the reproductive tract, remain to be vastly improved. Post-2015, a sustainable development agenda presents to India valuable opportunities to not only provide universal reproductive health care but also prioritize efforts to evolve a holistic approach with a strong commitment to discuss, deliberate, and disseminate knowledge and information in reproductive health sciences and medicine.
•Administration of oral or intra-vaginal antibiotics is the routine treatment of infection and inflammation of the reproductive tract.•Application of probiotics for a prolonged period of time is considered to be an attractive supplementary and/or alternative regimen for re-establishment of vaginal homeostasis.•Design of novel antigen-sparing therapy demands a thorough knowledge of resident microbiota in different body niches and the metabolome they exude.•Turnover of microbiome due to different physiological responses needs to be evaluated to develop personalized medicine.
Perceived stress and stress reduction interventions have a mixed relationship with fecundity. The objective of this study is to attempt and disentangle these relationships by looking at practicing stress reduction techniques and fecundity and examining their relationship to a behavioral and a neuroendocrine measure of stress. Fifty nulliparous-infertile women participated in a randomized prospective pilot study with repeated measures to examine the efficacy of cognitive behavioral interventions (CBI) in reducing perceived stress and improving pregnancy rates. Stress measures were taken at T0 (before CBI), T2 (ovum pick up) and T3 (time of pregnancy test). We found that women who reported low perceived stress at the beginning of treatment (T0) had a twofold increased chance of becoming pregnant (βhCG >7 mIU/mL) compared to those who reported high-perceived stress, regardless of CBI. Women who received CBI reported reduced perceived stress at the time of the pregnancy test (T3). Women who engaged in daily practice of CBI had significantly higher pregnancy rates compared to those who did not practice. It may be beneficial for women who have high perceived stress levels to learn and practice stress reduction techniques before beginning IVF treatment, and continue to practice daily during IVF treatment.
Endometrial carcinomas (ECs) are the most common gynecologic malignancies, exceeding the incidence of ovarian and cervical cancers in elderly women (post-menopausal) in Western countries. Evidence suggests that it is a luteinizing hormone (LH) dependent disease. ECs overexpress LH/human chorionic gonadotropin (hCG) receptors as compared with pre and post-menopausal endometria. Activation of the LH/hCG receptors in primary and immortalized EC cells results in an increased cell proliferation and invasion, which are mediated by cyclic AMP(cAMP)/protein kinase A (PKA) signaling, require the presence of LH/hCG receptors, activation of β1 integrin receptors and an increase in the secretion of metalloproteinase-2 (MMP-2) in its active form. In addition to the endometrium, LH actions in the ovaries and adrenal glands results in an increased secretion of androgens, which are aromatized into estrogens in the adipose and EC tissues. LH also has direct effects in the pancreas, which results in an increase in insulin secretion, which in turn can also stimulate ovarian stromal cell proliferation, luteinization, androgens secretion and aromatization in adipose and EC tissues. LH is further elevated in post-menopausal women who develop EC as compared with post-menopausal women who do not develop the disease. These findings support complex network of LH actions that promote EC development in elderly women.
Extravillous trophoblasts (EVTs) invade the decidual stroma (interstitial trophoblast) and thereby attach the placenta to the uterus. They also invade toward spiral arteries (endovascular trophoblast) for the establishment of the uteroplacental blood flow. The latter does not start before the end of the first trimester of pregnancy. A new type of extravillous trophoblast invading into uterine glands (endoglandular trophoblast) has been described recently opening uterine glands toward the intervillous space of the placenta to enable histiotrophic nutrition. This review gives an overview about the different subtypes of EVTs and presents novel peculiarities in the field of EVT invasion. EVTs invade more structures in the maternal decidua than previously assumed. Especially a proper invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of pregnancy than assumed so far.
A significant proportion of pregnancy related complications like preterm birth, preeclampsia, intra-uterine growth restriction (IUGR) and spontaneous abortion may be due to defects at various stages of embryo implantation process, in particular, placentation. One of these defects is impaired syncytialization. This may also be responsible for low success rate of embryo implantation during Assisted Reproductive Technology (ART). As it is an early differentiation event of the trophectoderm, unveiling its elementary molecular network might help in understanding the cause behind such complications and even ameliorate the success rate of pregnancies. Therefore, the current review highlights the available information with respect to effector molecules such as syncytins, syndecan-1, CD98, connexin-43, proteases and protease convertase in trophoblast syncytialization. Promotion of syncytialization by EGF, hCG, IGFs, LIF etc. and its inhibition by TGF-β1 and TNF-α is also discussed. The signaling pathways, such as PKA-CREB, MAPK, STAT, Wnt/β-catenin etc. through which various factors modulate the process of syncytialization have also been presented. Post-transcriptional regulation via microRNAs has also been discussed. The information provided in this review will help in our understanding of the molecular mechanisms associated with syncytialization and their implications in pregnancy related complications.
Foetal immunotolerance is one of the major challenges of pregnancy which is surmounted in part by both, the foetus and the mother. This review highlights the role of two decidual proteins, galectin-1 and glycodelin A (GdA) in achieving localized immunosuppressive state in the uterus. The two proteins have similar effects on T cells, inhibiting their proliferation, inducing apoptosis, inhibiting IL-2 production, but, helping in the expansion of Treg cells. They also induce tolerogenicity in dendritic cells, B cells and monocytes. In addition, GdA suppresses the lytic activity of cytotoxic T cells and induces apoptosis in monocytes as well as NK cells. Overall, galectin-1 and GdA inhibit the proliferation of immune cells, decrease their cytotoxicity and induce an anti-inflammatory cytokine environment. Thus leading to modulation of the immune response at the feto-maternal interface aiding in the maintenance of pregnancy to full term. The two proteins, other than having overlapping functions share similarity only in being lectins. Both are structurally different; galectin-1 has a non-glycosylated β-sandwich while GdA has a glycosylated β-barrel. Evolutionarily, GdA is found only in higher primates and appears to be functionally restricted to pregnancy, whereas galectin-1 is found in most mammals and has a role in immunomodulation at almost all immune privileged sites.
Perceived stress and stress reduction interventions have a mixed relationship with fecundity. The objective of this study is to attempt and disentangle these relationships by looking at practicing stress reduction techniques and fecundity and examining their relationship to a behavioral and a neuroendocrine measure of stress.Fifty nulliparous-infertile women participated in a randomized prospective pilot study with repeated measures to examine the efficacy of cognitive behavioral interventions (CBI) in reducing perceived stress and improving pregnancy rates. Stress measures were taken at T0 (before CBI), T2 (ovum pick up) and T3 (time of pregnancy test).We found that women who reported low perceived stress at the beginning of treatment (T0) had a twofold increased chance of becoming pregnant (βhCG >7 mIU/mL) compared to those who reported high-perceived stress, regardless of CBI. Women who received CBI reported reduced perceived stress at the time of the pregnancy test (T3). Women who engaged in daily practice of CBI had significantly higher pregnancy rates compared to those who did not practice.It may be beneficial for women who have high perceived stress levels to learn and practice stress reduction techniques before beginning IVF treatment, and continue to practice daily during IVF treatment.
Human embryonic stem cells (hESCs), owing to their potential promise to develop into any somatic cell type, have radicalized biotechnology research and application in clinical medicine. The source of hESCs has traditionally been viable cells retrieved from preimplantation stage embryos grown in culture in IVF-ET clinics. The present article deals with various crucial moral, ethical and governance issues pertaining to biomedical research and clinical application using hESCs. We have also addressed the progress of clinical translation of hESC biotechnology from its inception to the present scenario and its consequent societal impact today. Additionally, various safety factors which are to be instituted before clinical applications of hESC products to patients have been discussed. Finally, the ethical progress about the dilemma between treating the hESC as potential ‘human being’ and as an instrument to alleviate the sufferings of human race has been examined from various scientific and epistemic perspectives.
Timed administration of endometrial scratching in natural cycles followed by IVF-ET reportedly yields improved clinical pregnancy in women. In the present study, we have examined the issue of endometrial transcriptomic response in natural cycles preceding to the intervention cycles of IVF-ET to explore the differences, if any, in transcript expression profiles between those who conceived and those who did not following endometrial scratching in IVF-ET. Patients (n = 25) undergoing autologous IVF-ET cycles with history of failed IVF-ET/ICSI cycles underwent endometrial scratching and sampling during 12–18 day of untreated cycles preceding to intervention. Each patient was monitored for pregnancy outcome using the routine protocol. Each sample was subjected to whole genome expression array experiment (n = 20) followed by exploratory and differential display analysis. Endometrial whole genome transcriptomics of two groups (pregnancy positive, n = 10; pregnancy negative, n = 10) revealed that samples mutually clustered primarily based on pregnancy outcome. The secretory maturation of endometrium was seen to involve pathways related to oxidative phosphorylation, ubiquinone metabolism, cellular adhesion, skeletal and motor activities, and transcription and translation regulation. Additionally, genes related to neurogenesis and synaptogenesis, chemokines associated with cell adhesion, and developmental signalling were up-regulated in samples obtained from pregnancy-positive women. Further, patients with affected endometrial expression of genes involved in gynaecological neoplasm and transcriptional dysregulation in natural cycles did not conceive in IVF-ET. Transcriptomic expressions in endometrium yielded information with predictive value of pregnancy outcome following endometrial scratching in women with history of repeated implantation failure upon IVF-ET.
Blastocyst hatching is a prerequisite for successful implantation. Knowledge on this phenomenon is scarce in humans and the available information stems from studies on rodents. In hamsters, we earlier showed that embryo-derived cathepsin (Cat) proteases (Cat-L, -B and -P) are involved in blastocyst hatching and it is governed by a few molecular regulators. Here, we assessed the involvement of NF-κB signaling in blastocyst development and hatching. Hamster embryos, recovered from super-ovulated hamsters, were cultured in the absence or presence of NF-κB inhibitors (BAY-11-7082 or JSH-23). Development through peri-hatching stages and hatching rates were scored. Embryonic mRNA and protein expressions analyzed for NF-κB and Cats (-L, -B, -P); their levels correlated with hatching rates; their cellular immuno-localizations were examined. Transcript and protein expression of NF-κB components (IKK, Rel-A and IκB-b) were observed in 8-cell embryos through hatched-blastocysts. The NF-κB inhibitors (BAY-11-7082 and JSH-23) inhibited blastocyst hatching in a dose-dependent manner; percentages being 37.8 ± 3% and 36.5 ± 2.8%, respectively; >90% hatching in untreated-controls. NF-κB inhibition lead to a peri-hatching inflated-state of blastocysts, in contrast to deflated-state observed with control blastocysts. Also, NF-κB signaling inhibition-mediated reduction in hatching rates were accompanied by significant reductions in transcript and protein levels of Cat-L, -B and -P. We conclude that NF-κB signaling components are expressed during peri-hatching blastocyst development and that it is important for blastocyst hatching. Our results provide the first evidence for the involvement of NF-κB transcription-factor in mammalian blastocyst hatching phenomenon.
Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein expressed exclusively in the gonads. This hormone is an important regulator of the early growth of follicles through inhibitory effects on the recruitment of primordial follicles into the pool of growing follicles and on granulosa cell proliferation. Cystic ovarian disease (COD) is an important disorder affecting the fertility of dairy cattle. In the present study, we evaluated the expression of AMH in granulosa cells and AMH secretion into follicular fluid in pre-ovulatory follicles from control cows, animals with spontaneously arising COD and during the development of the disease, at 5, 10 and 15 days of follicular persistence. To this end, after an oestrous synchronization protocol, low doses of progesterone was administered for 5, 10 and 15 days after the expected day of ovulation (day 0 of follicular persistence) in treated cows (groups P5, P10 and P15, respectively), using an intravaginal progesterone-releasing device. Results showed a decrease in the expression of AMH in granulosa cells throughout folliculogenesis (P <0.05) and in the spontaneously arising follicular cysts and persistent follicles related to the control group (P <0.05). There was also a higher concentration of AMH in the follicular fluid of persistent follicles at 10 and 15 days of follicular persistence (P <0.05). Together, these results may indicate an alteration in AMH expression and secretion, which occurs early in folliculogenesis and incipiently during the development of COD, and which could contribute to the recurrence of this disease in cattle.
