Overview of the expression patterns and roles of Lipocalin 2 in the reproductive system.

The 25 kDa-sized protein Lipocalin 2 (LCN2) was originally isolated from human neutrophil granulocytes more than 30 years ago. LCN2 is an emerging player in innate immune defense, as it reduces bacterial growth due to its ability to sequester iron-containing bacterial siderophores. On the other hand, LCN2 also serves as a transporter for various hydrophobic substances due to its ß-barrel shaped structure. Over the years, LCN2 has been detected in many other cell types including epithelial cells, astrocytes, and hepatocytes. Studies have clearly shown that aberrant expression of LCN2 is associated with a variety of disorders and malignancies, including several diseases of the reproductive system. Furthermore, LCN2 was proposed as a non-invasive prognostic and/or diagnostic biomarker in this context. Although several studies have shed light on the role of LCN2 in various disorders of the female and male reproductive systems, including tumorigenesis, a comprehensive understanding of the physiological function of LCN2 in the reproductive tract is still lacking. However, there is evidence that LCN2 is directly related to fertility, as global depletion of Lcn2 in mice has a negative effect on their pregnancy rate. Since LCN2 expression can be regulated by steroid hormones, it is not surprising that its expression fluctuates greatly during remodeling processes in the female reproductive tract, especially in the uterus. Well-founded details about the expression and regulation of LCN2 in a healthy reproductive state and also about possible changes during reproductive aging could contribute to a better understanding of LCN2 as a target in various diseases. Therefore, the present review summarizes current knowledge about LCN2 in the reproductive system, including studies in rodents and humans, and discusses changes in LCN2 expression during pathological events. The limited data suggest that LCN2 is expressed and regulated differently in healthy male and female reproductive organs.

Preliminary testing of "roadmap to parenthood" decision aid and planning tool for family building after cancer: Results of a single-arm pilot study.

OBJECTIVE: Many young adult female cancer survivors need to use reproductive medicine, surrogacy, or adoption to have a child. This study pilot tested Roadmap to Parenthood, a web-based, self-guided decision aid and planning tool for family building after cancer (disease agnostic). METHODS: A single-arm pilot study tested feasibility, acceptability, and obtained effect size estimates of the Roadmap tool. Participants, recruited via hospital-based and social media strategies, completed a baseline survey (T1), accessed the Roadmap tool (website), then completed surveys at one- and 3-months (T2 and T3, respectively). Feasibility and acceptability were evaluated with rates of eligibility, enrollment, and survey completion, and feedback. Pairwise t-tests and repeated measures ANOVA evaluated usage effects. Effect size estimates were calculated. RESULTS: Participants (N = 98) averaged 31 years old (SD = 5.61); 71% were nulliparous. Enrollment rate was 73%, T1-T2 completion rate was 80%, and 93% accessed the website. From T1-T2, participants reported improvements in decisional conflict (p < 0.001; Cohen's d = 0.85), unmet information needs (p < 0.001; Cohen's d = 0.70), self-efficacy (p = 0.003; Cohen's d = 0.40), and self-efficacy for managing negative emotions (p = 0.03; Cohen's d = 0.29); effects were sustained at T3. There was no change in reproductive distress (p = 0.22). By T3, 94% reported increased consideration of preparatory actions and 20%-61% completed such actions. CONCLUSIONS: The Roadmap intervention was feasible to conduct, acceptable to users, and led to improvements in key psychosocial outcomes. Future directions will test intervention efficacy in a randomized controlled trial with a larger sample and over a longer period. A web-based tool may help women make decisions about family building after cancer and prepare for potential challenges.

Polycystic ovary syndrome (PCOS): progress towards a better understanding and treatment of the syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. It has a strong hereditary component estimated at 60 to 70% in daughters. It has been suggested that environmental factors during the fetal period may be involved in the development of the syndrome in adulthood. However, the underlying mechanisms of its transmission remain unknown, thus limiting the development of effective therapeutic strategies.This article highlights how an altered fetal environment (prenatal exposure to high levels of anti-Müllerian hormone) can contribute to the onset of PCOS in adulthood and lead to the transgenerational transmission of neuroendocrine and metabolic traits through alterations in the DNA methylation process.The originality of the translational findings summarized here involves the identification of potential biomarkers for early diagnosis of the syndrome, in addition to the validation of a promising therapeutic avenue in a preclinical model of PCOS, which can improve the management of patients suffering from the syndrome.

Le syndrome des ovaires polykystiques (SOPK) est le trouble endocrinien et métabolique le plus répandu chez les femmes en âge de procréer, avec une forte composante héréditaire estimée entre 60 et 70%. Les facteurs environnementaux pendant la période fœtale pourraient être impliqués dans l'apparition du syndrome à l'âge adulte. Néanmoins, les mécanismes sous-jacents à sa transmission demeurent inconnus, limitant ainsi le développement de thérapies efficaces.Cet article met en lumière comment un environnement fœtal altéré (exposition prénatale à des taux élevés d'hormone anti-müllerienne) pourrait contribuer à la survenue du SOPK chez la descendance ainsi qu'à la transmission transgénérationnelle des caractéristiques neuroendocriniennes et métaboliques du SOPK, par le biais d'une altération du processus de la méthylation de l'ADN.L'originalité des travaux translationnels présentés ici repose d'une part sur l'identification de potentiels biomarqueurs de diagnostic précoce du syndrome. Et d'autre part, sur la validation d'une piste thérapeutique prometteuse dans un modèle préclinique de SOPK, offrant ainsi des perspectives d'amélioration de la prise en charge des patientes atteintes de ce syndrome.

Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches.

Early pregnancy loss is a primary cause of low reproductive rates in dairy cows, posing severe economic losses to dairy farming. The accurate diagnosis of dairy cows with early pregnancy loss allows for oestrus synchronization, shortening day open, and increasing the overall conception rate of the herd. Several techniques are available for detecting early pregnancy loss in dairy cows, including rectal ultrasound, circulating blood progesterone, and pregnancy-associated glycoproteins (PAGs). Yet, there is a need to improve on existing techniques and develop novel strategies to identify cows with early pregnancy loss accurately. This manuscript reviews the applications of rectal ultrasound, circulating blood progesterone concentration, and PAGs in the diagnosis of pregnancy loss in dairy cows. The manuscript also discusses the recent progress of new technologies, including colour Doppler ultrasound (CDUS), interferon tau-induced genes (ISGs), and exosomal miRNA in diagnosing pregnancy loss in dairy cows. This study will provide an option for producers to re-breed cows with pregnancy loss, thereby reducing the calving interval and economic costs. Meanwhile, this manuscript might also act as a reference for exploring more economical and precise diagnostic technologies for early pregnancy loss in dairy cows.

Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption.

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction.

Kisspeptins (KPs) are proteins that were first recognized to have antimetastatic action. Later, the critical role of this peptide in the regulation of reproduction was proved. In recent years, evidence has been accumulated supporting a role for KPs in regulating metabolic processes in a sexual dimorphic manner. It has been proposed that KPs regulate metabolism both indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, brown adipose tissue, and pancreas. The aim of the review is to provide both experimental and clinical evidence indicating that KPs are peptides linking metabolism and reproduction. We propose that KPs could be used as a potential target to treat both metabolic and reproductive abnormalities. Thus, we focus on the consequences of disruptions in KPs and their receptors in metabolic conditions such as diabetes, undernutrition, obesity, and reproductive disorders (hypogonadotropic hypogonadism and polycystic ovary syndrome). Data from both animal models and human subjects indicate that alterations in KPs in the case of metabolic imbalance lead also to disruptions in reproductive functions. Changes both in the hypothalamic and peripheral KP systems in animal models of the aforementioned disorders are discussed. Finally, an overview of current clinical studies involving KP in fertility and metabolism show fewer studies on metabolism (15%) and only one to date on both. Presented data indicate a dynamic and emerging field of KP studies as possible therapeutic targets in treatments of both reproductive and metabolic dysfunctions.

Biology and Toxicology of Gametes, Embryos, and Cancer Cells in Reproductive Systems.

Reproduction is the important process of transmitting one's genetic information to the next generation [...].

Pesticides exposure and compromised fitness in wild birds: Focusing on the reproductive endocrine disruption.

Exposure of pesticides to wildlife species, especially on the aspect of endocrine disruption is of great concern. Wildlife species are more at risk to harmful exposures to the pesticides in their natural habitat through diet and several other means. Species at a higher tropic level in the food chain are more susceptible to the deleterious effects due to sequential biomagnifications of the pesticides/metabolites. Pesticides directly affect fitness of the species in the wild causing reproductive endocrine disruption impairing the hormones of the gonads and thyroid glands as reproduction is under the influence of cross regulations of these hormones. This review presents a comprehensive compilation of important literatures on the impact of the current use pesticides in disruption of both the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes particularly in birds addressing impacts on the reproductive impairments and overall fitness. In addition to the epidemiological studies, laboratory investigations those provide supportive evidences of the probable mechanisms of disruption in the wild also have been incorporated in this review. To accurately predict the endocrine-disruption of the pesticides as well as to delineate the risk associated with potential cumulative effects, studies are to be more focused on the environmentally realistic exposure dose, mixture pesticide exposures and transgenerational effects. In addition, strategic screening/appropriate methodologies have to be developed to reveal the endocrine disruption potential of the contemporary use pesticides. Demand for adequate quantitative structure-activity relationships and insilico molecular docking studies for timely validation have been highlighted.

The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence.

OBJECTIVE: Organisms and cellular viability are of paramount importance to living creatures. Disruption of the balance between cell survival and apoptosis results in compromised viability and even carcinogenesis. One molecule involved in keeping this homeostasis is serum-glucocorticoid regulated kinase (SGK) 1. Emerging evidence points to a significant role of SGK1 in cell growth and survival, cell metabolism, reproduction, and life span, particularly in prenatal programming and reproductive senescence by the same token. Whether the hormone inducible SGK1 kinase is a major driver in the pathophysiological processes of prenatal programming and reproductive senescence? METHOD: The PubMed/Medline, Web of Science, Embase/Ovid, and Elsevier Science Direct literature databases were searched for articles in English focusing on SGK1 published up to July 2023 RESULT: Emerging evidence is accumulating pointing to a pathophysiological role of the ubiquitously expressed SGK1 in the cellular and organismal viability. Under the regulation of specific hormones, extracellular stimuli, and various signals, SGK1 is involved in several biological processes relevant to viability, including cell proliferation and survival, cell migration and differentiation. In line, SGK1 contributes to the development of germ cells, embryos, and fetuses, whereas SGK1 inhibition leads to abnormal gametogenesis, embryo loss, and truncated reproductive lifespan. CONCLUTION: SGK1 integrates a broad spectrum of effects to maintain the homeostasis of cell survival and apoptosis, conferring viability to multiple cell types as well as both simple and complex organisms, and thus ensuring appropriate prenatal development and reproductive lifespan.

An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum.

BACKGROUND: Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. METHODS: We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4',6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male ß-alanyl-tryptamine (BATT) was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone ß-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum's reproductive and oviposition processes. CONCLUSIONS: We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production.

Evaluation of Chronic Effects of Potassium Chloride and Nickel on Survival, Growth, and Reproduction of a Unionid Mussel (Lampsilis siliquoidea).

The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Disruption of Thyroid Hormone Receptor Thrab Leads to Female Infertility in Zebrafish.

Thyroid hormones (THs) T4 and T3 are vital for development, growth, and metabolism. Thyroid dysfunction can also cause problems in fertility, suggesting involvement of THs in reproduction. In zebrafish, there exist 2 forms of TH receptor alpha gene (thraa and thrab). Disruption of these genes by CRISPR/Cas9 showed no reproductive irregularities in the thraa mutant; however, inactivation of the thrab gene resulted in female infertility. Although young female mutants (thrabm/m) showed normal ovarian development and folliculogenesis before sexual maturation, they failed to release eggs during oviposition after sexual maturation. This spawning failure was due to oviductal blockage at the genital papilla. The obstruction of the oviduct subsequently caused an accumulation of the eggs in the ovary, resulting in severe ovarian hypertrophy, abdominal distention, and disruption of folliculogenesis. Gene expression analysis showed expression of both TH receptors and estrogen receptors in the genital papilla, suggesting a direct TH action and potential interactions between thyroid and estrogen signaling pathways in controlling genital papilla development and function. In addition to their actions in the reproductive tracts, THs may also have direct effects in the ovary, as suggested by follicle atresia and cessation of folliculogenesis in the heterozygous mutant (thrab+/m), which was normal in all aspects of female reproduction in young and sexually mature fish but exhibited premature ovarian failure in aged females. In summary, this study provides substantial evidence for roles of THs in controlling the development and functions of both reproductive tract and ovary.

Cadmium toxicity to and accumulation in a soil collembolan (Folsomia candida): major factors and prediction using a back-propagation neural network model.

Accurate prediction of cadmium (Cd) ecotoxicity to and accumulation in soil biota is important in soil health. However, very limited information on Cd ecotoxicity on naturally contaminated soils. Herein, we investigated soil Cd ecotoxicity using Folsomia candida, a standard single-species test animal, in 28 naturally Cd-contaminated soils, and the back-propagation neural network (BPNN) model was used to predict Cd ecotoxicity to and accumulation in F. candida. Soil total Cd and pH were the primary soil properties affecting Cd toxicity. However, soil pH was the main factor when the total Cd concentration was < 3 mg kg-1. Interestingly, correlation analysis and the K-spiked test confirmed nutrient potassium (K) was essential for Cd accumulation, highlighting the significance of studying K in Cd accumulation. The BPNN model showed greater prediction accuracy of collembolan survival rate (R2 = 0.797), reproduction inhibitory rate (R2 = 0.827), body Cd concentration (R2 = 0.961), and Cd bioaccumulation factor (R2 = 0.964) than multiple linear regression models. Then the developed BPNN model was used to predict Cd ecological risks in 57 soils in southern China. Compared to multiple linear regression models, the BPNN models can better identify high-risk regions. This study highlights the potential of BPNN as a novel and rapid tool for the evaluation and monitoring of Cd ecotoxicity in naturally contaminated soils.

Disruption of gonadotropin hormone biosynthesis by parabens: A potential development and reproduction-associated adverse outcome pathway.

Parabens are widely used as antibacterial preservatives in foods and personal care products. The knowledge about the modes of toxic action of parabens on development and reproduction remain very limited. The present study attempted to establish a development and reproduction-associated adverse outcome pathway (AOP) by evaluating the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on the biosynthesis of gonadotropins, which are key hormones for development and reproduction. MP and BP significantly upregulated the mRNA and protein levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary gonadotropic cells in a concentration-dependent manner. Activation of gonadotropin-releasing hormone receptor (GnRHR) was required for gonadotropin biosynthesis induced by BP, but not MP. Molecular docking data further demonstrated the higher binding efficiency of BP to human GnRHR than that of MP, suggesting GnRHR as a potential molecular initiative event (MIE) for BP-induced gonadotropin production. L-type voltage-gated calcium channels (VGCCs) were found to be another candidate for MIE in gonadotropic cells response to both MP and BP exposure. The calcium-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 was subsequently required for MP- and BP-induced activation of GnRHR and L-type VGCCs pathways. In summary, MP and BP promoted gonadotropin biosynthesis through their interactions with cellular macromolecules GnRHR, L-type VGCCs, and subsequent key event ERK1/2. This is the first study to report the direct interference of parabens with gonadotropin biosynthesis and establish a potential AOP based on pathway-specific mechanism, which contributes to the effective screening of environmental chemicals with developmental and reproductive health risks.

Reproductive and Oncologic Outcomes in Young Women with Stage IA and Grade 2 Endometrial Carcinoma Undergoing Fertility-Sparing Treatment: A Systematic Review.

BACKGROUND: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3-5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. METHODS: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. RESULTS: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. CONCLUSIONS: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions.

Harnessing the power within: engineering the microbiome for enhanced gynecologic health.

Abstract: Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions. Lay summary: Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.

Male manipulation impinges on social-dependent tumor suppression in Drosophila melanogaster females.

Physiological status can influence social behavior, which in turn can affect physiology and health. Previously, we reported that tumor growth in Drosophila virgin females depends on the social context, but did not investigate the underlying physiological mechanisms. Here, we sought to characterize the signal perceived between tumorous flies, ultimately discovering that the tumor suppressive effect varies depending on reproductive status. Firstly, we show that the tumor suppressive effect is neither dependent on remnant pheromone-like products nor on the microbiota. Transcriptome analysis of the heads of these tumorous flies reveals social-dependent gene-expression changes related to nervous-system activity, suggesting that a cognitive-like relay might mediate the tumor suppressive effect. The transcriptome also reveals changes in the expression of genes related to mating behavior. Surprisingly, we observed that this social-dependent tumor-suppressive effect is lost in fertilized females. After mating, Drosophila females change their behavior-favoring offspring survival-in response to peptides transferred via the male ejaculate, a phenomenon called "male manipulation". Remarkably, the social-dependent tumor suppressive effect is restored in females mated by sex-peptide deficient males. Since male manipulation has likely been selected to favor male gene transmission, our findings indicate that this evolutionary trait impedes social-dependent tumor growth slowdown.

Knockout of ecdysis triggering hormone receptor (ETHr) gene adversely affects the nymphal molting and adult reproduction in Bemisia tabaci.

Bemisia tabaci (Gennadius) is one of the most dangerous polyphagous pests in the world causing damage to various crops by sucking sap during the nymphal and adult stages. Chemical management of whiteflies is challenging because of the emergence of pesticide resistance. RNA interference has been well established in whitefly to study the functions of various genes. G-protein coupled receptors (GPCRs) are important targets for development of new generation insecticides. In this study, Ecdysis triggering hormone receptor (ETHr) gene expression was recorded in different stages of whitefly and its function has been studied through RNAi. The expression of ETHr is highest in third-instar nymphs followed by other nymphal instars, pupae and newly emerged adults. Silencing of ETHr resulted in significantly higher adult mortality (68.88%), reduced fecundity (4.46 eggs /female), reduced longevity of male and female (1.05 and 1.40 days, respectively) when adults were fed with dsETHr @ 1.0 µg/µl. Silencing of ETHr in nymphs lead to significantly higher mortality (81.35%) as compared to control. This study confirms that ETHr gene is essential for growth and development of whitefly nymphs and adults. Hence, it can be future target for developing dsRNA based insecticides for management of whitefly.

Day length regulates gonadotrope proliferation and reproduction via an intra-pituitary pathway in the model vertebrate Oryzias latipes.

In seasonally breeding mammals and birds, the production of the hormones that regulate reproduction (gonadotropins) is controlled by a complex pituitary-brain-pituitary pathway. Indeed, the pituitary thyroid-stimulating hormone (TSH) regulates gonadotropin expression in pituitary gonadotropes, via dio2-expressing tanycytes, hypothalamic Kisspeptin, RFamide-related peptide, and gonadotropin-releasing hormone neurons. However, in fish, how seasonal environmental signals influence gonadotropins remains unclear. In addition, the seasonal regulation of gonadotrope (gonadotropin-producing cell) proliferation in the pituitary is, to the best of our knowledge, not elucidated in any vertebrate group. Here, we show that in the vertebrate model Japanese medaka (Oryzias latipes), a long day seasonally breeding fish, photoperiod (daylength) not only regulates hormone production by the gonadotropes but also their proliferation. We also reveal an intra-pituitary pathway that regulates gonadotrope cell number and hormone production. In this pathway, Tsh regulates gonadotropes via folliculostellate cells within the pituitary. This study suggests the existence of an alternative regulatory mechanism of seasonal gonadotropin production in fish.

Cumulative effect of arsenic on the number of mouse offspring and the female reproductive hormones in mice.

In this study, we evaluated the cumulative effects of arsenic (III) oxide on the number of mouse offspring over three consecutive generations and monitored changes in levels of the reproductive hormones, oestradiol and progesterone in female mice during the dioestrus phase of the cycle. The control group received water from the mains. In two experimental groups, mice were given drinking water containing dissolved arsenic (III) oxide at concentrations of 10.6 mg L-1 and 106 mg L-1, respectively. These concentrations represent the values converted from a human model to an animal model (mice) thus correspond to the arsenic content of the groundwater in the southern part of the Pannonian Basin, in the province of Vojvodina, in the Banat region, in particular in the town of Zrenjanin. The average number of newborn mice in both experimental groups decreased for three consecutive generations. The total arsenic content of day-old mice did not show significant differences between the experimental groups. Arsenic (III) oxide affected the reproductive hormone levels of female mice at both concentrations.