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Reproductive function in female mammals is largely orchestrated by the hypothalamic-pituitary-gonadal axis, which generates rhythmic hormonal fluctuations underlying the estrous cycle. Part of this cycle, the preovulatory LH surge, is tightly gated by the circadian system. The suprachiasmatic nucleus (SCN)-the central circadian clock-plays a critical role in this temporal regulation and among SCN-derived signals, neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) have been proposed to mediate this process. Notably, most SCN neurons are GABAergic; however, the contribution of SCN-derived GABAergic transmission in the female reproductive system remains unclear. To investigate the role of GABAergic output from the SCN, we first performed AAV-mediated SCN ablation in Vgat-IRES-Cre mice (Vgat; encoding the vesicular GABA transporter), resulting in disrupted estrous cycles. To assess GABAergic transmission from specific SCN populations, we next examined Avp-Vgat-/- and Vip-Vgat-/- mice, in which the Vgat gene is selectively deleted in AVP or VIP neurons. Vip-Vgat-/- females showed regular cycles. However, Avp-Vgat-/- females exhibited marked disruptions, and AAV-mediated Vgat rescue in AVP neurons in the SCN (SCN-AVP) restored normal estrous cycles. Anterograde tracing revealed dense SCN-AVP terminals in the anteroventral periventricular nucleus (AVPV), which contains kisspeptin neurons, but few projections to other major reproductive neuroendocrine populations. These findings suggest GABAergic output from SCN-AVP neurons stabilizes the estrous cycle, potentially via kisspeptin neurons in the AVPV, thereby highlighting that GABAergic signaling also contributes to female reproductive regulation alongside AVP and VIP.Significance Statement The circadian system must precisely coordinate the timing of ovulation, and is essential for maintaining a stable estrous cycle. Although most neurons in the master clock are GABAergic, their role in reproductive control remains unknown. Here, our study identifies GABAergic signaling from arginine vasopressin neurons in the master clock as a key regulator of the estrous cycle. Loss of this signaling disrupts estrous cyclicity, and its restoration rescues regular cycling. This finding highlights GABA release from arginine vasopressin neurons as an additional component of reproductive control, alongside established peptidergic regulators such as arginine vasopressin and vasoactive intestinal peptide. This work advances our understanding of how the brain's circadian system organizes complex reproductive physiology through multiple neural output pathways.

Endometriosis is a chronic inflammatory condition affecting 10% to 15% of reproductive-aged women. The urinary tract is the second most common extragenital site of endometriosis after the gastrointestinal tract, with a prevalence of 15% to 50% of women with deep endometriosis (DE). The urinary bladder is the most common site of urinary tract involvement (85%), followed by the ureter (10%), kidney (4%), and urethra (2%). Urinary bladder (anterior compartment) and ureter (mediolateral compartment) involvement are considered different disease entities. Patients with bladder involvement are more symptomatic with dysuria, urinary frequency, and recurrent urinary tract infections. Ureteral involvement is more commonly due to extrinsic compression, but may be intrinsic, involving the ureteral mucosa or muscularis. Hematuria is a rare presenting symptom of both bladder and ureteral involvement. Malignant transformation of urinary tract endometriosis is rare; however, DE involvement of the urinary tract may be mistaken for malignancy. Radiologists need a high index of suspicion for endometriosis in reproductive-aged women, and recognition of urinary tract involvement is important for timely treatment.

Seminal plasma can have wide-ranging effects on reproductive fitness-from affecting sperm fertilization capacity and female reproductive physiology to influencing offspring viability and health. Seminal plasma can also change in response to environmental conditions including diet, which of itself is known to affect reproductive traits and fitness outcomes. However, an understanding of how paternal diet alters seminal plasma composition and how these effects relate to fetal development remains elusive. Here, we applied the geometric framework for nutrition to systematically manipulate dietary macronutrient balance in male mice and determine dietary effects on the seminal vesicle fluid (SVF; comprising much of the seminal plasma) proteome, as well as relate differences in the proteome to aspects of fetal development. We (i) identified the largest number of proteins in the mouse SVF proteome to date, (ii) determined a set of proteins that were significantly affected by dietary macronutrients, (iii) showed that differences in a protein related to lipid mobilization and metabolism (APOA4) were correlated with fetal development, and (iv) detected dietary effects on aspects of fetal development that were unrelated to SVF protein abundance. This study provides a comprehensive characterization of the male SVF proteome across nutritional space and highlights potential functional ways in which male diet and the seminal plasma may mediate fitness.

The toxicity of nanoplastics (NPs) and plastic additives such as phthalates, recognized endocrine-disrupting chemicals, remains insufficiently understood, particularly regarding their combined effects on male reproductive health across the lifespan. Since these contaminants can cross biological barriers, including the placenta, this study, grounded in the developmental origins of health and disease (DOHaD) concept, evaluated the effects of gestational and lactational exposure to NPs and a phthalate mixture (PM) on testicular development and function in male offspring. Pregnant SD rats were allocated to six groups: control (CTRL); T1 (20μg/kg/day PM); T2 (200mg/kg/day PM); T3 (NPs: 1mg/kg/day,100nm); T4 (20μg/kg/day PM+NPs); and T5 (200mg/kg/day PM+NPs). Animals were exposed orally from gestational day 10 to postnatal day (PND)21. Male offspring were euthanized at PND22 (prepuberty) and PND120 (adulthood). At PND22, increased apoptosis in pachytene spermatocytes was observed in the T5 group compared with the CTRL, along with altered gene expression, including increased Amh (T4 vs.T1) and Srd5a1 (T1-T4 vs.CTRL) and reduced Ar expression (T3 vs.CTRL). At PND120, the exposure decreased seminiferous tubule diameter (T2), epithelial height (T1-T5), and numbers of Sertoli (T2-T5) and Leydig cells (T4 and T5) compared to the CTRL. Histopathological alterations were more incident in the T1, T3, T4, and T5 compared to the CTRL, and reduced Tjp1 expression in co-exposed animals suggested impairment of the blood-testis barrier. Redox analyses revealed age-dependent worsening of oxidative stress, particularly in co-exposure groups. Overall, gestational co-exposure to phthalates and NPs disrupts testicular morphology, gene regulation, and redox balance, indicating synergistic and persistent reproductive toxicity.

In the 19th and early 20th centuries, many fetuses and infants were collected for anatomical study. Yet little research has explored their origins or the ethical implications of holding and using these individuals in teaching and research. This paper reviews the literature on fetal and infant skeletal collections and presents a case study from the W. D. Trotter Anatomy Museum in Aotearoa New Zealand that uses the lens of biopower and necropolitics to examine the acquisition and use of these individuals in anatomical education. This model highlights how societal and institutional powers and medicine regulate reproductive bodies and determine the perceived worth of fetuses and infants within specific cultural, historical, and medical contexts. This case study shows that individuals were often acquired from marginalized populations-unwed parents, the impoverished, and institutionalized women-whose reproductive autonomy was politically and socially negated. The paper explores how biopower and the necropolitics of reproduction in colonial New Zealand operated to control populations and individuals. Biopower and the necropolitics of reproduction were enacted through eugenic sentiment, structural inequality in healthcare, alongside medical and institutional control over the living and the dead. This contributed to higher infant mortality for marginalized mothers and infants, a loss of autonomy over the fate of deceased bodies, and the suppression of grief. The anatomization of fetuses rendered them objects of scientific value, whilst simultaneously erasing their personhood and socio-historical context, thus extending the structural violence their families experienced during life into their postmortem "life" history (necro-violence).

European populations of the grey partridge (Perdix perdix L.) have declined rapidly, necessitating captive breeding programs to supplement wild populations. Artificial insemination could optimize these reproductive efforts, yet specific protocols are lacking. This study evaluated the effects of short-term liquid storage (24 h at 5 &#xb0;C in EK and Lake extenders) on selected semen quality parameters and determined how extender type and sperm dose affects fertility level. Semen was collected from 15 males, pooled, diluted 1:2 and evaluated in vitro at 0 h and after 24 h of storage. Sperm motility and kinematics were assessed using Sperm Class Analysis system, whereas viability and morphology were evaluated by nigrosin-eosin staining. Obtained data was analyzed using repeated measures ANOVA. Fertilization outcomes, assessed by incubating eggs laid following artificial insemination, were analyzed using generalized linear mixed models. Storage significantly reduced sperm motility, viability and the proportion of morphologically normal spermatozoa (P < 0.05). The EK extender better preserved sperm viability and normal morphology, whereas the Lake extender maintained a more stable kinetic profile over the time. Fresh ejaculates naturally exhibited a remarkably low proportion of morphologically normal spermatozoa (14.2%). In vivo, sperm dose significantly affected fertilization success (P < 0.05); with higher doses (&#x2265; 16 &#xd7; 106 spermatozoa) consistently resulting in higher fertility rates in both fresh and stored semen. Extender type did not significantly affect fertilization rates. Progressive motility showed a tendency to predict fertilization success after storage (P = 0.06). Despite reduced in vitro semen quality, short-term liquid storage of grey partridge semen can be effectively applied in artificial insemination procedures when an adequate sperm dose is used. These findings provide a practical basis for improving reproductive management and developing genetic resource conservation strategies in this species.

Per- and polyfluoroalkyl substances (PFAS) have become an important focus of research in recent years due to their widespread use and environmental persistence. Perfluorooctanoic acid (PFOA) has attracted considerable attention due to its effects on the reproductive system, yet its molecular mechanisms in testicular cells remain unclear. This study aimed to investigate the effects of PFOA on oxidative stress, mitochondrial function, and interconnected programmed cell death pathways. Mouse Sertoli (TM4) and spermatogonial (GC-1) cells were exposed to PFOA at concentrations of 200-800&#xb5;M for 24h, and its effects on cell viability and cytotoxicity were evaluated. Oxidative stress levels were determined by measuring reactive oxygen species production, malondialdehyde levels, antioxidant enzyme activities, and mitochondrial membrane potential. In addition, the potential cell death pathways, including apoptosis, autophagy, mitophagy, and ferroptosis, were assessed by analyzing gene and protein expression using RT-qPCR and Western blot. PFOA exposure resulted in a concentration-dependent and significant increase in intracellular ROS levels, accompanied by a significant decrease in mitochondrial membrane potential in both cell lines. The antioxidant defense system and NRF2 signaling were markedly suppressed. PFOA exposure also significantly activated intrinsic apoptotic pathways, as supported by increased apoptotic gene expression and elevated caspase-3 protein levels. A clear increase in autophagy- and mitophagy-related markers was observed, suggesting that cells develop an adaptive response to mitochondrial damage. These findings provide important mechanistic insights into mitochondrial dysfunction and associated cell death processes in PFOA-exposed testicular cells.

Sertoli cells (SCs) play a vital role in the seminiferous tubules, as they are involved in maintaining the microenvironment, providing structural and nutritional support for germ cells, and modulating the process of spermatogenesis. 3-Monochloropropane-1,2-diol (3-MCPD), a common food-processing contaminant, is known to impair male reproduction by interfering with SC function. However, the underlying toxicological mechanisms of 3-MCPD in SCs have not been fully elucidated. In this study, primary rat SCs exposed to 3-MCPD were analyzed using tandem mass tag (TMT)-based proteomics. A total of 285 differentially expressed proteins (DEPs) were identified, including 165 upregulated and 120 downregulated proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enrichment analyses revealed that 3-MCPD exposure significantly affected pathways related to glutathione (GSH) metabolism, oxidative stress response, retinoic acid (RA) metabolism, and meiosis. Biochemical assays demonstrated that 3-MCPD exposure profoundly reduced intracellular GSH reserves and increased reactive oxygen species (ROS) levels. RT-qPCR validation confirmed the changes of key functional genes, including Crabp1, Rdh10, Rbp1, ErbB3/4, Hmox1, Nqo1, Star, and Gstm1. Importantly, exogenous RA supplementation not only restored the impaired meiotic paracrine signaling molecules Nrg1/3 but also alleviated ROS accumulation and redox imbalance. These findings elucidate the comprehensive proteomic alterations in SCs induced by 3-MCPD and reveal a novel functional crosstalk between RA signaling and oxidative balance, offering new insights into potential intervention strategies against reproductive toxicity.

This study aimed to evaluate the feasibility of using indocyanine green (ICG) to assess vascularisation by visualizing ovarian fluorescence after laparoscopic cystectomy or plasmajet therapy. The secondary objective was to assess its potential as a surgical marker for predicting the risk of ovarian reserve impairment. The research design was a prospective feasibility study conducted in the gynecological surgery department at Clermont Ferrand University Hospital. A total of 45 participants aged 18 to 42&#xa0;years who required laparoscopic surgical treatment for a benign ovarian cyst (<10&#xa0;cm in diameter) were included in the study. The participants underwent laparoscopic cystectomy or plasmajet therapy with intraoperative evaluation of ovarian vascularisation using ICG fluorescence. Ovarian reserve was assessed using AMH levels and AFC at baseline (M0) and at 6 and 12&#xa0;months postoperatively (M6 and M12). Pregnancy outcomes were also recorded. Fluorescence was observed in 100% of cases, with Likert scores &#x2265;3 in 80% of the participants. No adverse effects related to ICG were identified. No correlation was found between ICG intensity and ovarian reserve measures. Postoperative follow-up demonstrated a decrease in AMH levels at M6, followed by a halt in this decline at M12 with a tendency toward amelioration halt at M12(2.42 [1.12; 2.71] at M0 then 1.23 [0.37; 2.23] ng/mL at M6; p&#xa0;<&#xa0;0.001) then 1.46 [0.66; 2.67] ng/mL at M12; p&#xa0;<&#xa0;0.342) and increased AFC (M0: 11 [8; 18] ; M&#xa0;+&#xa0;6: 17 [9; 20]; p&#xa0;=&#xa0;0.018 ; M&#xa0;+&#xa0;12: 19 [12; 27]; p&#xa0;=&#xa0;0.001). Among the 26 participants who desire pregnancy, 38.5% conceived spontaneously, and 16% were referred to Assisted Reproductive Technology (ART). The use of ICG fluorescence is a feasible approach to the intraoperative assessment of ovarian vascularisation. However, its utility in guiding clinical decisions remains to be demonstrated.

The plasticizers, phthalates, have attracted extensive attention due to their ubiquitous existence in various environments and potential adverse health impacts. Dibutyl phthalate (DBP) is one of the most commonly used phthalate plasticizers, andcan cause poly-biotoxicity, e.g., reproductive and developmental toxicity, endocrine disruption, neurological impairment, metabolic dysregulation, cellular stress responses, and negatively affect lipid metabolism on muptiple aquatic organisms. In this study, we deciphered the impacts of DBP on growth, reproduction, and glycerolipid metabolism in the cladoceran Daphnia magna. The results demonstrated that, DBP exposure significantly impaired survival, reducing lifespan by 21 %-27 % at &#x2265; 0.8 mg/L concentrations in F0 daphnids. However, maternal exposure to DBP induced transgenerational attenuation in F1 offspring, and only the total number of neonates, number of neonates per brood and age at first reproduction were prominently affected. The glycerolipids, including the storage triacylglycerol, the glycolipid monogalactosyldiacylglycerolipid, and the phospholipids, phosphatidylchloline and phosphatidylinositol, all notably accumulated in daphnids exposed to 0.8 mg/L of DBP, while the sphingomyelin exhibited significant degradation compared to the vehicle control. DBP exposure prominently altered fatty acyl composition of membrane lipids in daphnids, with pronounced redistribution of omega-3 and omega-6 fatty acids across glycerolipid classes. Thus, DBP caused maternal impacts on D. magna, and the inhibited growth and blocked propagation were differentiated between F0 and F1 daphnids. Glycerolipid remodeling dependent on polyunsaturated fatty acids was essential for daphnids in acclimation to DBP stress. These findings provide mechanistic insights into phthalate-induced biotoxicity in aquatic organisms, highlighting glycerolipid remodeling as a critical response pathway.

Establishing mouse models expressing heterologous major histocompatibility complex class I (MHC-I) molecules is an effective strategy for immunological research. However, murine &#x3b2;2-microglobulin (m&#x3b2;2m) may interfere with the proper folding and peptide loading of the heterologous heavy chain. We found that m&#x3b2;2m can associate with SLA-1*1502 and the Porcine reproductive and respiratory syndrome virus (PRRSV)-derived epitope peptide (PPs) to form a complex, albeit with lower efficiency compared with swine &#x3b2;2m (s&#x3b2;2m). We determined the crystal structure of the chimeric complex SLA-1*1502/m&#x3b2;2m/PP7. Comparison with the previously reported SLA-1*1502/s&#x3b2;2m/PP7 structure revealed that, although the overall conformations are similar, the interaction pattern between the heavy and light chains differs, exhibiting features characteristic of both murine and porcine origins. Interestingly, the peptide binding mode in the chimeric complex also exhibited distinct local features: the buried surface area between PP7 and the binding groove increased, and a new salt bridge was formed between PP7 and residue R114 of SLA-1*1502. Structural comparison of diverse cross-species chimeric complexes reveals that conformational shifts of bound epitope peptides are governed by the stability of the core hydrogen-bond network at the heavy-light chain interface, and substitution with human &#x3b2;2m triggers milder local structural distortions than murine &#x3b2;2m. In summary, our findings demonstrate that the differences between m&#x3b2;2m and s&#x3b2;2m influence both complex formation and peptide binding mode. Therefore, constructing mouse models co-expressing SLA-I and s&#x3b2;2m would be a more optimized strategy for related immunological studies.

Brucellosis remains a critical public health and economic concern in Bangladesh due to its zoonotic transmission and severe reproductive losses in cattle. This study evaluated the safety, immunogenicity, and field effectiveness of an experimentally developed inactivated alum-adjuvanted Brucella abortus biovar 3 vaccine prepared from a local strain, using BALB/c mice for safety assessment and dairy cattle for field evaluation. A total of 1,570 dairy cattle from 30 farms across 6 regions were enrolled, of which 1,227 were vaccinated and 343 remained unvaccinated. Animals were monitored for one year using serological assays, including RBPT and i-ELISA, molecular confirmation by AMOS-ERY PCR, and cellular immune response assessment through delayed-type hypersensitivity testing and histopathology. Vaccinated cattle developed detectable antibody responses by 15 d post-vaccination, with titers peaking at 90 d and remaining elevated compared with baseline and unvaccinated controls up to 180 d post-vaccination. Delayed-type hypersensitivity responses and histopathological findings further supported vaccine-induced cellular immunity at antigen-injected sites. Field evaluation showed a marked reduction in seropositive abortion, with total abortions declining from 89 before vaccination to 33 after vaccination. During the post-vaccination period, seropositive abortion occurred in 1 of 1,227 vaccinated cattle and 32 of 343 unvaccinated cattle. After accounting for farm-level clustering, vaccination remained strongly associated with reduced abortion risk. The cluster-robust Poisson model estimated an adjusted risk ratio of 0.0074, corresponding to an adjusted vaccine effectiveness of 99.26% (95% CI: 94.08-99.91%). Mixed-effects logistic and farm-clustered GEE models produced comparable estimates, supporting the robustness of the finding. No adverse effects were recorded in either mice or cattle, and vaccine sterility was confirmed by culture, indicating the absence of viable bacteria. These findings indicate that the locally developed inactivated alum-adjuvanted B. abortus vaccine is safe, immunogenic, and strongly associated with reduced seropositive abortion under farm-clustered field conditions, supporting its potential use as part of brucellosis control strategies in Bangladesh.