Female Reproduction Research Articles

Regulatory Involvement of Kisspeptin in Energy Balance and Reproduction.

The hypothalamic-pituitary-gonadal axis, which regulates steroidogenesis and germ cell formation, closely regulates the reproduction process. Nonetheless, other chemical mediators, such as kisspeptin, influence this axis. Kisspeptin is a hypothalamic neuropeptide that modulates the function of this axis and also plays a central role in energy balance. The present study reviews the impact and associated mechanisms of kisspeptin on male and female reproduction based on available evidence in the literature. Kisspeptin and its neurons exert anorexigenic activity, thus maintaining adequate energy balance for optimal reproductive function. Also, they stimulate the release of GnRH, resulting in the optimal performance of gonadal physiological processes viz. production of steroid sex hormones and germ cells. However, studies linking kisspeptin to reproduction are yet scanty. Hence, studies exploring the upstream and downstream signaling pathways activated by kisspeptin concerning reproduction in an attempt to better understand the associated mechanisms of the regulatory activities of kisspeptin on reproduction are recommended. In addition, potential factors that may modulate kisspeptin activities may be useful in the management of infertility and perhaps, in the development of contraceptives for those who do not intend to achieve conception.

Antimony exposure affects oocyte quality and early embryo development via excessive mitochondrial oxidation and dysfunction

Antimony (Sb) is a metalloid, widely presents in the environment and associates with human health. In this study, we aimed to decipher whether Sb exposure is harmful to female reproduction and explore the underlying mechanisms. The ICR mice were exposed to 0, 5, 10, and 20 mg/kg acetate potassium Sb tartrate trihydrate by intraperitoneal injection for 10 days, then mouse oocytes were collected for further analysis. We first found a significant decrease in the proportion of MII-stage oocytes obtained from supernumerary ovulation in the fallopian tubes and early embryo development under Sb treatment. Then a series of tests showed Sb affects oocyte maturation by damaging the cytoskeleton of microtubule and actin. Moreover, the abnormal distribution of cortical granules and their component Ovastacin in oocytes, combined with reduced expression levels of Juno, affected sperm-oocyte binding and led to fertilization failure. Based on the sequencing results and experimental validation, it was demonstrated that Sb exposure impairs mitochondrial distribution and membrane potential, elevated levels of mitochondrial superoxide, finally caused energy supply deficits. Mitochondrial damage in oocytes after Sb exposure results in the excessive oxidative stress and early apoptosis. Taken together, these data suggest that Sb exposure decreases oocyte quality and female fertilization ability by impairing mitochondrial function and redox perturbation.

DCAF2 is essential for the development of uterine epithelia and mouse fertility.

The successful outcome of a pregnancy depends on the proper functioning uterine epithelium. DNA damage binding protein 1 and cullin 4-associated factor 2 (DCAF2), a conserved substrate receptor for the cullin 4-RING E3 ubiquitin ligase (CRL4) complex, is essential for maintaining genome stability by facilitating ubiquitin-mediated degradation of substrates. To better understand the physiological role of DCAF2 in female reproduction, we conducted a study using mice with conditional knockout (cKO) of DCAF2 in the uterus using the progesterone receptor Cre (Pgr Cre/+) mouse model. Our results showed the cKO mice were completely infertile, despite having ovarian function. The cKO mice exhibited severely thin uteri, demonstrating notable defects in both the uterine epithelium and a lack of glands. In addition, there were impaired proliferation and differentiation of epithelial cells in the cKO mice, ultimately resulting in failed implantation. Moreover, through deciphering the uterine transcriptome of cKO mice, we revealed crucial differentially expressed genes associated with steroid signaling. Further experiments have demonstrated cKO mice exhibit elevated uterine PGR signaling and reduced estrogen receptor signaling, although the levels of progesterone and estrogen remained unaltered. These alterations may contribute to defects in epithelium. Overall, our findings highlight a previously unrecognized but indispensable role for DCAF2 in the development of uterine luminal and glandular epithelium by orchestrating PGR and estrogen receptor responses. Its deficiency in the uterus leads to mouse infertility.

Oocytes maintain low ROS levels to support the dormancy of primordial follicles.

Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.

Visfatin (NAMPT) expression in human placenta cells in normal and pathological conditions and its hormonal regulation in trophoblast JEG-3 cells.

Visfatin is an adipokine involved in energy metabolism, insulin resistance, inflammation, and female reproduction. Due to limited data about its action in the human placenta, the aims of our studies included the analysis of visfatin expression and immunolocalization in trophoblast cell lines JEG-3 and BeWo as well as in human placentas from normal and pathological pregnancies. Moreover, we also checked the hormonal regulation of visfatin levels and the molecular mechanism of observed changes in JEG-3 cells. Cell culture and placental fragments collection along with statistical analysis were performed using standard laboratory procedures also described in our previous papers. We demonstrated an increased gene and protein expression of visfatin in JEG-3, BeWo cells, while variable expression in maternal and fetal parts of normal/ pathological pregnancy placentas. In addition, the immunolocalization of visfatin was observed in the cytoplasm of both cell lines, the capillary epithelium of the maternal part and syncytiotrophoblasts of the placental fetal part; in all tested pathologies, the signal was also detected in decidual cells. Furthermore, we demonstrated that hormones: progesterone, estradiol, human chorionic gonadotropin, and insulin increased the visfatin levels in JEG-3 cells with the involvement of specific signaling pathways. Taken together, differences in the expression and localization of visfatin between normal and pathological placentas suggested that visfatin may be a potential marker for the diagnosis of pregnancy disorders. In addition, we found that placental levels of visfatin can be regulated by hormones known to modulate the function of placental cells.

Cumulative and interannual effects of reproduction in eastern grey kangaroos.

Reproduction can reduce energy allocation to other life-history traits such as survival and growth. Resource constraints give rise to (co)variation in life-history traits and to heterogeneity in energy acquisition and allocation. At each reproductive opportunity, females face a choice between allocation to current reproduction or to maintenance. Many studies compare reproductive trade-offs between two consecutive years, but few account for the cumulative effects of reproduction over multiple years, a crucial factor in understanding life-history evolution in long-lived iteroparous species. We compared short- (interannual) and long-term (cumulative) reproductive trade-offs with a 14-year capture-mark-recapture study of eastern grey kangaroos, where females can have substantial skeletal growth for several years after maturation. We used a multivariate approach to compare how interannual and multi-annual cumulative reproduction affected growth (n = 378 measurements), mass change (n = 376 measurements) and subsequent reproduction (n = 388 measurements), and to quantify (co)variation between these traits among individuals (n = 107) and years (n = 14). Interannually, young females that reproduced experienced decreased skeletal growth compared to young females that did not reproduce. Reproductive females of all ages experienced reduced mass gain and weaning probability in the following year. The cumulative effects of multiple reproductions included decreased skeletal growth, mass gain and weaning probability in the following year. These effects increased with age and reproductive rate. We found positive trait correlations between mass change, leg growth and subsequent reproduction among individuals and years, though weaker at the cumulative than interannual level. Females experience dynamic interannual and cumulative trade-offs. Our analyses of cumulative costs of reproduction revealed long-term trade-offs as well as cumulative costs that were not apparent when estimating interannual costs. Trait correlations suggested heterogeneity in growth and reproduction among females. Years of increased growth were followed by years of increased reproduction, and years of poor growth were followed by years of poor reproduction. Our exploration of both interannual and cumulative costs of reproduction underscores the need to account for long-term reproductive histories to better understand reproductive trade-offs in long-lived iteroparous species.

NEURO-ENDOCRINE ASPECTS OF INFERTILITY IN WOMEN WITH LONG-COVID-19

Currently, the exact mechanisms of the impact of COVID-19 on women's reproductive health remain poorly defined. Purpose of the study is to assess the hormonal function of patients with infertility and long-term COVID-19. Materials and methods. The main group consisted of 80 women with infertility who had symptoms of "long-COVID", the comparison group - 40 patients without a history of COVID-19. Hormonal studies of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, melatonin, estradiol (E2), progesterone (P), free testosterone (Tf), dehydroepiandrosterone (DHEA), cortisol, anti-Müllerian hormone (AMH) were conducted. Results. Violation of gonadotropic regulation of reproductive function is manifested by an increase in the serum concentration of LH and FSH and an increase in their ratio. A tendency to hyperprolactinemia, a relative decrease in serum melatonin was revealed. A more than 2-fold increase in the E2/P ratio on the 22nd day of the menstrual cycle indicates a tendency to hyperestrogenemia. An increase in the level of serum androgens (Tf and DHEA), which also play a role in female reproduction, was detected. Elevated levels of the stress hormone cortisol can negatively affect the chances of getting pregnant in assisted reproductive technologies programs. A decrease in AMH was observed in patients with infertility and long-term COVID-19, indicating a decrease in their ovarian reserve. Conclusion. The identified neuro-endocrine changes in patients with infertility and long-term COVID-19, due to the direct and indirect effects of the transmitted disease and its consequences, may be a marker of reduced reproductive potential and unsuccessful attempts to use assisted reproductive technologies.

High early lactational synchrony within baboon groups predicts increased infant mortality.

Social group composition can have fitness implications for group members by determining opportunities for affiliative and competitive interactions. Female-female competition may be particularly acute when many groupmates have young infants at the same time, with potential consequences for infant survival. Here, we used decades of data on wild baboons (Papio sp.) in Amboseli, Kenya, to examine the effects of 'early lactational synchrony' (here, the proportion of females in a group with an infant <90 days old) on female-female agonistic interactions and infant survival. Because early lactation is an energetically demanding time for mothers and a risky time for infants, we expected early lactational synchrony to produce intensified competition for food and/or male protectors, resulting in more frequent female-female agonistic interactions and high infant mortality. In support of these predictions, we found that the frequency of female-female agonistic interactions increased with increasing early lactational synchrony. Reproductive state affected this relationship: while females in all states (cycling, pregnant, and postpartum amenorrhea) initiated more agonistic interactions when early lactational synchrony was high, only females in postpartum amenorrhea (including, but not limited to, females in early lactation) received more agonistic interactions. Furthermore, while high early lactational synchrony was rare, it strongly predicted infant mortality. This association may result from both aggression among adult females and infanticidal behavior by peripubertal females. These findings provide novel evidence that social dynamics may shape reproductive phenology in a nonseasonal breeder. Specifically, both competition among reproductive females and harassment from nonreproductive females may select against synchronous reproduction.

Association of LIN28B Gene Polymorphisms with Intrauterine Adhesions in Patients after Curettage Abortion.

Background/Objectives: Intrauterine adhesion (IUA) is characterized by endometrial fibrocyte hyperplasia. The LIN28B gene is associated with many proliferative diseases. However, its association with IUA is entirely unknown. We hypothesized that LIN28B gene polymorphisms are responsible for IUA susceptibility after curettage abortion. Methods: In this genetic association study, We genotyped two common polymorphisms (rs369065 C>T and rs314280 A>G) in 107 patients with IUA and 270 controls without IUA after curettage abortion from a Chinese population between July 2022 and May 2023 and analyzed their associations with IUA risk using multiple logistic regression models. Results: The carriers of genotype rs314280 AA of the LIN28B gene showed an increased risk of IUA (AOR [adjusted odds ratio] = 2.12, 95% CI [confidence interval] = 1.151-3.903), compared to GG+GA genotypes. Further stratification analyses showed that the deleterious role of the rs314280 AA genotype was more evident in patients with fewer than four pregnancies (AOR = 2.740, 95% CI = 1.355-5.540), fewer than two births (AOR = 2.676, 95% CI = 1.300-5.509), and fibrous (AOR = 2.082, 95% CI = 1.084-3.997) and muscular adhesions (AOR = 3.887, 95% CI = 1.116-13.540). However, the rs369065 T>C polymorphism of the LIN28B gene was not significantly associated with the occurrence of IUA. Conclusions: The rs314280 AA genotype of the LIN28B gene is associated with an increased risk of IUA in patients after curettage abortion, especially in those with fewer pregnancies or parities and higher disease severity. Our findings implicate a precise choice of clinical counseling and decision-making of IUA, thereby protecting female reproduction.

Unraveling the impact of hyperleptinemia on female reproduction: insights from transgenic pig model

BackgroundInfertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear.MethodsTransgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated.ResultsTransgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary.ConclusionsLow body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Genetic determinants of age at menarche: does the LIN28B gene play a role? A narrative review.

Menarche, the first menstrual period marking the onset of female reproduction, is a milestone of female puberty. The timing of menarche determines the timing of later phases of pubertal maturation in girls and has major implications for health later in life, including behavioral and psychosocial disorders during adolescence and fertility problems and increased risk for certain diseases in adulthood. Over the last few decades, a continuous decline in age at menarche has been noted, with environmental factors contributing to this change in the timing of menarche. However, a genetic component of age at menarche and pubertal onset has been strongly suggested by studies in families and twins wherein up to approximately 80% of the variance in puberty onset can be explained by heritability. Gene association studies have revealed several genetic loci involved in age at menarche, among which LIN28B has emerged as a key regulator of female growth and puberty. LIN28B, a human homolog of Lin28 of C. elegans, is a known RNA-binding protein that regulates let-7 microRNA biogenesis. Genome-wide association studies have identified the association of polymorphisms in the LIN28B gene with age at menarche in several population cohorts worldwide. In this paper, we review the genetic factors contributing to age of menarche, with particular focus on the identified polymorphisms in LIN28B gene.

CORRELATION BETWEEN THE DISORDER OF THE THYROID GLAND, OBESITY AND OVERWEIGHT IN THE FEMALE GENDER

Introduction: The thyroid gland is the endocrine gland responsible for the production of thyroid hormones, a regulator of growth, development and basal metabolic rate of the organism. It also has a wide range of physiological effects on the organism such as: general thermogenesis, physiological metabolic effects, growth and developmental features and when these parameters move up and down they lead to acute or chronic pathology. Pathologies of the thyroid gland are very frequent diseases in our country, especially in the female gender. As far as diseases are concerned, when we have iodine deficiency, imbalance of thyroid hormone values such as an increase that leads to hyperthyroidism or a decrease in values that leads to hypothyroidism, other diseases such as Hashimoto's, Graves etc. Obesity is a state of metabolic disorders, sometimes considered a disease in which excess body fat is accumulated to such an extent that it can negatively affect human health. Obesity is related to the function of the thyroid gland and this metabolic disorders is a very frequently in reproductive female. Body BMI is measured with a metric formula where body weight (in kg) divided by body height (in m2) set to the square power gives us the body index-BMI (%) measure. Purpose of the study: This paper aims to investigate the correlation of thyroid gland disorders and hormonal imbalance with the phenomenon of body weight as the main causes of this metabolic disease . Material and method: The research will take a total of 80 patients, they will be divided by gender and age groups into three categories. The first group will include patients from: 15 to 20 years, the second group from: 21 to 50 years and the third group from: 51 to 70 years. From the patients included in the research, blood samples will be taken and the hormones will be analyzed: TSH, FT4, FT3 also BMI will be measured. The data will be processed with serum and will be analyzed by means of the modern automatic method enzyme Fluorescent Immunoassay (Biomerie). The BMI of the body will be measured with a metric formula where the weight of the patient (in kg) divided by the height of the patient (in m2) set to the square power will give us the measure of body index-BMI (%). SPSS – Software package version 20.0 Numerical series were analyzed using central tendency measures (average, median, minimum values, maximum values), as well as distribution measures (standard deviation); To determine the regularity of the frequency distribution of the examined variables, the Shapiro-Wilk W Test was used; Non-parametric tests for two independent parameters were used to test the significance and difference between some numerical parameters with irregular frequency distribution (Mann Whitney U test); To determine statistical significance, a two-way analysis was used with a significance level (means) of p&lt;0.05. Research results: Endocrine disorders are more frequent and appear faster in the thyroid gland. Statistics show that there are millions of people affected by these metabolic syndrome problems. The results of the research will give a real insight into the function of the thyroid gland, the state of the level of hormonal status and the impact of metabolic syndrome of BMI, which can lead to hormonal imbalance and metabolic disorder. Conclusion: From the analyzes performed on patients of different age groups and genders, we come to the conclusion that: • Hormonal disorders of the thyroid gland can be the main cause of the BMI factor, • The correlation of thyroid hormone status and metabolic status are in continuous correlation with obesity, overweight, infertility, diabetes and hyperlipidemia. • These changes of the thyroid gland and the BMI can have negative consequences for human health such as in osteoporosis and electrolytes imbalance.

CEC04-04 Pollutants and female reproduction

CEC04-04 Pollutants and female reproduction

Effects of the symbiotic bacteria, Caballeronia insecticola, on the life history parameters of Riptortus pedestris (Hemiptera: Alydidae) and their implications for the host population growth.

This study aimed to investigate the effects of symbiosis on the life history of host insects and address their implications at the host population level. We evaluated the effects of symbiotic bacteria Caballeronia insecticola on its host Riptortus pedestris (Fabricus) (Hemiptera: Alydidae) from cohorts for nymphal development, adult survivorship, and female reproduction. Then, life table parameters were compared between symbiotic and apo-symbiotic groups, and the effects of symbiosis on the abundance of R. pedestris were simulated for varying proportions of symbiotic individuals in host populations. We found that symbiosis significantly accelerated the nymphal development and reproductive maturation of females. However, symbiosis incurred survival cost on adult females, reducing their longevity by 28.6%. Nonetheless, symbiotic females laid significantly greater numbers of eggs than the apo-symbiotic during early adult ages. This early reproductive investment negated the adverse effect of their reduced longevity, resulting in the mean lifetime fecundity to not significantly differ between the 2 groups. Indeed, total cohort fecundity of the symbiotic group was 1.3-fold greater than that of the apo-symbiotic group. Life table analysis demonstrated shorter generation time and greater population growth rate in the symbiotic population. Finally, the simulation model results indicate that an increase in the proportion of symbiotic R. pedestris favored the population growth, increasing the population size by 1.9 times for every 25% increase in the proportion of symbiotic individuals. Our study demonstrates that symbiont-mediated changes in the life history parameters of host individuals favor the host population growth, despite substantial reduction in the female longevity.

Introduction to the Symposium: An Integrative Look at Whole-organism Trade-offs from the Female-centered Perspective of Biology.

Trade-offs during reproduction have long been a central focus within biology and much of the foundational work within life history evolution has focused on females, as the fitness of females is more easily quantified for use in theoretical models. However, in many regards, the field of organismal biology has deviated from this early focus on females, particularly as it relates to the nuances and dynamic nature of female reproduction. Regardless, at the organismal level, reproduction is thought to trade-off with other simultaneously occurring processes. Recent papers have sought to outline the issues with our current understanding of whole-organism trade-offs, though the field as a whole has not come to a consensus on what trade-offs mean to a reproducing female. To rectify this important gap in how trade-offs are discussed in organismal biology as well as confusion about what constitutes a trade-off, our overarching goal of this symposium was to discuss trade-offs from an integrative perspective that places female reproduction at the center. By answering what trade-offs are and what they mean to reproducing females, what has been neglected in the context of whole-organism physiology, and how maternal effects fit within this framework, our group of speakers and their associated papers will crystalize nuances of measuring and determining presence (if any) of trade-offs in reproducing females in a range of taxa and subfields.

Modelling the complete life cycle of an arctic copepod reveals complex trade-offs between concurrent life cycle strategies

Calanus hyperboreus is a large-bodied, biomass dominant species that performs a crucial ecosystem energy transfer by converting the spring phytoplankton bloom into lipid reserves that fuel the higher trophic levels of the Gulf of St. Lawrence (GSL) pelagic ecosystem, including the critically endangered North Atlantic right whale (Eubalena glacialis). Given that the GSL, the southernmost core habitat of C. hyperboreus, is undergoing rapid warming, developing a population model allows us to synthesize existing knowledge of the species, and to examine the species response to environmental conditions. To simulate the multi-year life cycle in the northwest GSL, model equations are implemented for ingestion, assimilation, respiration, egg production, stage development, mortality, and vertical migration behaviors including dormancy entry and exit. The 1-D particle-based model predicts the evolution of individual stage, structural mass, lipid, age, sex, abundance, and egg production, as well as the seasonal evolution of the population structure in the northwest GSL. Individual lipid-based thresholds inform the timing of ontogenetic vertical migration. Life cycle targets defined from a literature review are used to guide model parameterization and assess its performance. The simulated population structure, phenology, and size at stage are generally consistent with observations. Under 10 years of repeat year forcing, the model simulates a quasi-stable overwintering population composed of late stages CIV, CV and CVI. Observations suggest that stage CIV is the first overwintering stage in the GSL, and point to the occurrence of iteroparous females. Using the model, the relative success of diverse dormancy and reproductive phenotypes are explored. Second reproduction females reproduce earlier in winter than first reproduction females, with implications for the ability of the new generation to match the spring bloom and accumulate sufficient lipid to overwinter as stage CIV. Without iteroparity, the time window of reproduction contracts and the population is reduced, underscoring the role of a flexible multi-year life cycle in population success.

Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis.

Stanniocalcin (STC) 1 and 2 serve as antihyperglycemic polypeptide hormones with critical roles in regulating calcium and phosphate homeostasis. They additionally function as paracrine and/or autocrine factors involved in numerous physiological processes, including female reproduction. STC1 and STC2 contribute to the pathophysiology of several diseases, including female infertility- and pregnancy-associated conditions, and even tumorigenesis of reproductive organs. This comprehensive review highlights the dynamic expression patterns and potential dysregulation of STC1 and STC2, restricted to female fertility, and infertility- and pregnancy-associated diseases and conditions, such as endometriosis, polycystic ovary syndrome (PCOS), abnormal uterine bleeding, uterine polyps, and pregnancy complications, like impaired decidualization, preeclampsia, and preterm labor. Furthermore, the review elucidates the role of dysregulated STC in the progression of cancers of the reproductive system, including endometrial, cervical, and ovarian cancers. Additionally, the review evaluates the expression patterns and prognostic significance of STC in gynecological cancers by utilizing existing public datasets from The Cancer Genome Atlas to help decipher the multifaceted roles of these pleiotropic hormones in disease progression. Understanding the intricate mechanisms by which STC proteins influence all these reviewed conditions could lead to the development of targeted diagnostic and therapeutic strategies in the context of female reproductive health and oncology.

Casein kinase 1α mediates estradiol secretion via CYP19A1 expression in mouse ovarian granulosa cells

BackgroundCasein kinase 1α (CK1α), expressed in both ovarian germ and somatic cells, is involved in the initial meiosis and primordial follicle formation of mouse oocytes. Using in vitro and in vivo experiments in this study, we explored the function and mechanism of CK1α in estrogen synthesis in mice ovarian granulosa cells.MethodsA CK1α knockout (cKO) mouse model, targeted specifically to ovarian granulosa cells (GCs), was employed to establish the influence of CK1α on in vivo estrogen synthesis. The influence of CK1α deficiency on GCs was determined in vivo and in vitro by immunofluorescence analysis and Western blot assay. Transcriptome profiling, differentially expressed genes and gene functional enrichment analyses, and computation protein–protein docking, were further employed to assess the CK1α pathway. Furthermore, wild-type female mice were treated with the CK1α antagonist D4476 to elucidate the CK1α's role in estrogen regulation.ResultsOvarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E2) level in the serum of cKO female mice were decreased by 57.3% and 87.4% vs. control mice, respectively.This deficiency disrupted the estrous cycle and enhanced the apoptosis in the GCs. We observed that CK1α mediated the secretion of estradiol in mouse ovarian GCs via the cytochrome P450 subfamily 19 member 1 (CYP19A1).ConclusionsThese findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis.Trial registrationNot applicable.

Icariin as a Treatment Proposal in Mammalian Reproduction.

Icariin (ICA), one of the main active components of Herba Epimedii, is a natural prenylated flavonol glycoside that possesses a wide range of pharmacological effects, including antioxidant, antiosteoporotic, anti-aging, neuroprotective, immunomodulatory, antitumor, and aphrodisiac effects, and prevents numerous health disorders, such as cardiovascular diseases, osteoporosis, cancer, sexual dysfunction, menstrual disorders, neurodegenerative diseases, asthma, chronic inflammation, and diabetes. In the reproductive system, it has been observed that ICA may play a role in preserving fertility by regulating different signalling pathways, such as PI3K/AKT, which improves ovarian function, and ERα/Nrf2, which enhances testicular function and prevents ROS generation. In contrast, regulating the NF/kB signalling pathway causes anti-inflammatory effects, reducing spontaneous abortions. In this study, we review and examine the relevant literature on the therapeutic potential of ICA in reproduction, highlight the various mechanisms of action and limitations for the therapeutic applications of ICA, and summarise and highlight the existing preclinical research on its effects on male and female reproduction.

Variants in NLRP2 and ZFP36L2, non-core components of the human subcortical maternal complex, cause female infertility with embryonic development arrest.

The subcortical maternal complex (SCMC), which is vital in oocyte maturation and embryogenesis, consists of core proteins (NLRP5, TLE6, OOEP), non-core proteins (PADI6, KHDC3L, NLRP2, NLRP7), and other unknown proteins that are encoded by maternal effect genes. Some variants of SCMC genes have been linked to female infertility characterized by embryonic development arrest. However, so far, the candidate non-core SCMC components associated with embryonic development need further exploration and the pathogenic variants that have been identified are still limited. In this study, we discovered two novel variants [p.(Ala131Val) and p.(Met326Val)] of NLRP2 in patients with primary infertility displaying embryonic development arrest from large families. In vitro studies using 293T cells and mouse oocytes, respectively, showed that these variants significantly decreased protein expression and caused the phenotype of embryonic development arrest. Additionally, we combined the 'DevOmics' database with the whole exome sequence data of our cohort and screened out a new candidate non-core SCMC gene ZFP36L2. Its variants [p.(Ala241Pro) and p.(Pro291dup)] were found to be responsible for embryonic development arrest. Co-immunoprecipitation experiments in 293T cells, used to demonstrate the interaction between proteins, verified that ZFP36L2 is one of the human SCMC components, and microinjection of ZFP36L2 complementary RNA variants into mouse oocytes affected embryonic development. Furthermore, the ZFP36L2 variants were associated with disrupted stability of its target mRNAs, which resulted in aberrant H3K4me3 and H3K9me3 levels. These disruptions decreased oocyte quality and further developmental potential. Overall, this is the first report of ZFP36L2 as a non-core component of the human SCMC and we found four novel pathogenic variants in the NLRP2 and ZFP36L2 genes in 4 of 161 patients that caused human embryonic development arrest. These findings contribute to the genetic diagnosis of female infertility and provide new insights into the physiological function of SCMC in female reproduction.