Glutamatergic and GABAergic neurons in the vLGN mediate the nociceptive effects of green and red light on neuropathic pain.

Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN, with red light increased more. In vLGN, green light causes a large increase in glutamatergic neurons, whereas red light causes a large increase in GABAergic neurons. Green light preconditioning increases the sensitivity of glutamatergic neurons to noxious stimuli in vLGN of PSL mice. Green light produces antinociception by activating glutamatergic neurons in vLGN, and red light promotes nociception by activating GABAergic neurons in vLGN. Together, these results demonstrate that different colors of light exert different pain modulation effects by regulating glutamatergic and GABAergic subpopulations in the vLGN. This may provide potential new therapeutic strategies and new therapeutic targets for the precise clinical treatment of neuropathic pain.

Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.

Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE. A bipolar electrode was implanted into hippocampal CA3 in male mice for kindling stimulation and EEG recording; a special promoter with enhanced synaptic activity-responsive element (E-SARE) was used to label seizure-activated neurons in the subiculum; the activity of subicular seizure-activated neurons was manipulated using chemogenetic approach; cognitive function was assessed in object location memory (OLM) and novel object recognition (NOR) tasks. We showed that chemogenetic inhibition of subicular seizure-activated neurons (mainly CaMKIIα+ glutamatergic neurons) alleviated seizure generalization and improved cognitive performance, but inhibition of seizure-activated GABAergic interneurons had no effect on seizure and cognition. For comparison, inhibition of the whole subicular CaMKIIα+ neuron impaired cognitive function in naïve mice in basal condition. Notably, chemogenetic inhibition of subicular seizure-activated neurons enhanced the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks. Our results demonstrate that subicular seizure-activated neurons contribute to cognitive impairment in TLE, suggesting seizure-activated neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Association between FSHR polymorphisms and polycystic ovary syndrome among Chinese women in north China.

PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder disease among women in reproductive-age. Since follicle stimulating hormone (FSH) exerts important biological functions, the association between PCOS and FSH receptor (FSHR) polymorphisms attracts wide attention. The aim of this study was to evaluate whether polymorphisms of FSHR at 307 and 680 codons are associated with PCOS patients in China. METHODS: Patients with PCOS (n = 215) and controls (n = 205) were recruited from Shanxi Province in north China. They are Han ethnics. Genomic DNA was isolated from the venous blood. The Ala307Thr and Ser680Asn polymorphisms of FSHR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. RESULTS: The distributions of genotype and allele of Ala307Thr and Ser680Asn polymorphisms of FSHR were not statistically different between the PCOS patients and the controls. Analysis of the frequency of FSHR polymorphisms showed no statistical difference among the PCOS patients with different obesity standards. Although there were no statistical differences in the most of the endocrine parameters including LH, LH/FSH, E2, P and T as well as the clinical pregnancy rate, there were significant differences in the levels of FSH and PRL among PCOS patients carrying different genotypes of Ala307Thr and Ser680Asn polymorphisms. CONCLUSION: The Ala307Thr and Ser680Asn polymorphisms of FSHR are not associated with PCOS in Han ethnic Chinese women in north China. The FSHR polymorphisms was related to the levels of FSH and PRL but not other PCOS-associated endocrine hormones as well as clinical pregnancy rate in PCOS patients of Han Chinese ethnical population.

Construction of a Multi-Indicator Model for Abscess Prediction in Granulomatous Lobular Mastitis Using Inflammatory Indicators.

Background: Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast disease, and abscess formation is a common complication of GLM. The process of abscess formation is accompanied by changes in multiple inflammatory markers. The present study aimed to construct a diagnosis model for the early of GLM abscess formation based on multiple inflammatory parameters. Methods: Based on the presence or absence of abscess formation on breast magnetic resonance imaging (MRI), 126 patients with GLM were categorised into an abscess group (85 patients) and a non-abscess group (41 patients). Demographic characteristics and the related laboratory results for the 9 inflammatory markers were collected. Logistics univariate analysis and collinearity test were used for selecting independent variables. A regression model to predict abscess formation was constructed using Logistics multivariate analysis. Results: The univariate and multivariate analysis showed that the N, ESR, IL-4, IL-10 and INF-α were independent diagnostic factors of abscess formation in GLM (P<0. 05). The nomogram was drawn on the basis of the logistics regression model. The area under the curve (AUC) of the model was 0.890, which was significantly better than that of a single indicator and the sensitivity and specificity of the model were high (81.2% and 85.40%, respectively). These results predicted by the model were highly consistent with the actual diagnostic results. The results of this calibration curve indicated that the model had a good value and stability in predicting abscess formation in GLM. The decision curve analysis (DCA) demonstrated a satisfactory positive net benefit of the model. Conclusion: A predictive model for abscess formation in GLM based on inflammatory markers was constructed in our study, which may provide a new strategy for early diagnosis and treatment of the abscess stage of GLM.

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

Objective: This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Conclusion: Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

[Effects on the secretion of reproductive hormones in adult female rats exposed to lipopolysaccharide in neonatal life].

OBJECTIVE: To explore whether neonatal endotoxin challenge alters reproductive hormone secretion in adult female rats. METHODS: Rats were intraperitoneally injected with lipopolysaccharide (LPS) or normal saline at postnatal days 3 and 5. At Week 12, the animals underwent bilateral oophorectomy and were exposed to LPS or saline. The secretion levels of luteinizing hormone (LH) and estradiol were measured. RESULTS: The LPS injection in adult neonatal saline rats caused the suppressed secretion of LH and estradiol. However, the decreased secretion of both LH and estradiol were much more apparent in adult neonatal LPS-treated rats. CONCLUSION: The neonatal LPS challenge alters the secretions of LH and estradiol during adulthood. And the mechanism may be mediated by epigenetic programming of hypothalamic-pituitary-gonadal axis.

SIRT7 silencing by miR-152-3p confers cell apoptosis and renal functional impairment induced by renal ischaemia/reperfusion injury.

PURPOSE: Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. METHODS: Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. RESULTS: SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3'-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. CONCLUSION: SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.

Effects of the Severe Acute Respiratory Syndrome Coronavirus 2 Inactivated Vaccine on the Outcome of Frozen Embryo Transfers: A Large Scale Clinical Study.

Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a life-threatening infectious disease that has become a global pandemic. Objective: This study aimed to explore the effects of SARS-CoV-2 inactivated vaccine on the outcome of frozen embryo transfer (FET). Methods: We grouped patients who underwent FET between August 2021 and March 2022 based on their vaccination status, number of doses, and the interval between the last dose and the FET, and then compared the differences in pregnancy outcomes among the groups. Results: There were 1084 vaccinated patients and 1228 non-vaccinated ones. There were significant differences in the live birth rate between the vaccination and non-vaccination groups (16.61% vs 28.26%), among the one-dose, two-dose, and three-dose groups (22.28% vs 19.51% vs 7.27%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (38.38% vs 27.27% vs 12.03%). There were significant differences in the persistent pregnancy rate between the vaccination and non-vaccination groups (22.88% vs 14.09%), among the one-dose, two-dose, and three-dose groups (14.51% vs 23.80% vs 38.18%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (1.01% vs 8.44% vs 28.16%). There were significant differences in the neonatal weight between the vaccination and non-vaccination groups [3805.50 (3746.00-3863.50) vs 2970.00 (2500.00-3400.00)]. There were significant differences in the premature birth rate among the one-dose, two-dose, and three-dose groups (23.26% vs 34.59% vs 100.00%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (15.79% vs 21.43% vs 37.00%). Conclusion: Pregnancy outcomes were not affected by taking the SARS-CoV-2 inactivated vaccine before FET, the number of doses, and the interval between doses. These findings provide evidence supporting the safety of administering the SARS-CoV-2 inactivated vaccine during pregnancy, which can be used as a guide for vaccinating patients undergoing ART.

The effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer-assisted reproduction.

OBJECTIVE: To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology. METHODS: The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis. RESULTS: After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was -.045 (p = .02), while the correlation coefficient between live birth and grouping was -.046. CONCLUSION: Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.

Correlation between methylenetetrahydrofolate reductase gene-specific methylation and recurrent spontaneous abortion.

OBJECTIVE: To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA). METHODS: A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA. RESULTS: The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P < 0.05). There was no significant difference in the TT genotype between the two groups (P > 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P < 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times. CONCLUSION: MTHFR gene-specific methylation can significantly increase the risk of RSA.

[A comparison of ultrasonography versus traditional approach for caudal block in children].

OBJECTIVE: To apply ultrasonic technology in positioning and monitoring for pediatric caudal blocks and compare it with traditional landmark approach and Swoosh test. METHODS: After obtaining the approval of hospital ethics committee and written parental informed consent, a total of 102 American Society of Anesthesiologists (ASA) I-II pediatric patients aged from 1 month to 8 years and scheduled for urologic or perineal surgery were recruited. Patients were randomly divided into 2 groups: ultrasound group (n = 52) and control group (n = 50). The sites of sacral cornu and sacral hiatus were determined by ultrasonic imaging or classic method of anatomical surface landmarks. Patients of two groups were punctured according to the scheduled site. Local anesthetic was injected slowly into caudal space after a successful caudal puncture and the positive reaction in caudal space was monitored simultaneously by ultrasound and classic swoosh test. The observational results and relevant date were recorded. RESULTS: In ultrasound and control groups, the number of puncture attempts was 1.10 ± 0.30 vs 1.56 ± 0.63, the duration of puncture (1.40 ± 0.39) vs (3.23 ± 1.23) min, the success rate at the first puncture attempt 90.4% vs 66% and the total puncture success rate 100% vs 92% respectively. After the injection of local anesthetic, the positive reaction rate of ultrasonography and swoosh test was 97.96% vs 62.24% respectively. All of above results in ultrasound group were superior to those in control group or with classic test. And the difference had statistical significance (P < 0.01). CONCLUSION: Ultrasonic positioning and monitoring for pediatric caudal block is both scientific and reasonable. The positioning detected by ultrasonic imaging is accurate and the monitoring results of ultrasound are reliable. It is obviously superior to traditional method and has clinical application values for caudal block in children.

[Effects of obesity on the lipid and glucose metabolism in female rats].

OBJECTIVE: To investigate the effects of obesity on the lipid and glucose metabolism in female rats. METHODS: The litter size was adjusted to 4 pups per litter for the small litter (SL, treatment group) and 12 neonates per dam in the normal litter (NL, controls) at postnatal day 0. Body weights were measured weekly. At the age of 6 weeks, bilateral ovariectomy was performed. The blood levels of free fat acid, triglyceride, total cholesterol, free blood glucose and free insulin were evaluated. The muscular expression of AMP-activated protein kinase was detected by immune staining. RESULTS: As compared to normal litters, the levels of fat acid, triglyceride, total cholesterol, free blood glucose and free insulin significantly increased. The muscular activity of AMP-activated protein kinase decreased. All difference were statistically significant (P < 0.05). CONCLUSION: Obesity in early life has obvious effects on the lipid and glucose metabolism in female rats.

[Effects of ru'ai shuhou recipe on the matrix metalloproteinases and the inhibitive factors in the recurrence and metastasis of HER2 positive breast cancer].

OBJECTIVE: To observe the anti-tumor recurrent and metastatic efficacy of Ru'ai Shuhou Recipe (RSR) on HER2 positive breast cancer, to evaluate the effects of RSR on the expressions of matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) in the recurrence and metastasis of HER2 positive breast cancer, thus revealing its anti-tumor recurrent and metastatic mechanisms. METHODS: Selected were 30-week-old HER2/neu transgenic spontaneous breast cancer mice FVB/neu. The primary tumor resection was carried out. After surgery they were randomly divided into the blank control group, the RSR group, the Herceptin group, and the combination group (RSR + Herceptin group). The treatment lasted for 4 months. The inhibition rate of the recurrent tumor volume and the inhibition rate of the lung metastasis were evaluated. The expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), and TIMP-2 in the recurrent tumor tissue were detected using Western blot. RESULTS: By the end of the treatment the average recurrent tumor volume was 11.11 +/- 8.71 cm3 in the blank control group and 5.56 +/- 5.55 cm3 of the RSR group, showing statistical difference between the two groups (P = 0.037). The average lung metastatic nodule was 16 in the blank control group and 10 in the RSR group. The inhibition rate of lung metastasis was 37. 85% in the RSR group, but with no statistical significance. The expression level of activated MMP-2 in the RSR group was down-regulated when compared with the blank control group, the Herceptin group, and the combination group (P < 0.05). The expression of MMP-9 of the RSR group, the Herceptin group, and the combination group was significantly down-regulated when compared with the blank control group (P < 0.05). The expression of MMP-9 of the RSR group and the combination group was further down-regulated when compared with the Herceptin group (P < 0.05). The expressions of both TIMP-1 and TIMP-2 of the RSR group, the Herceptin group, and the combination group were all up-regulated when compared with the blank control group (P < 0.05). The increased expression of TIMP-1 was more significantly in the RSR group and the combination group when compared with the Herceptin group (P < 0.05). It was higher in the combination group than in the RSR group (P < 0.05). CONCLUSIONS: RSR could inhibit the tumor recurrence of FVB/neu mice. It could reduce the degradation of extracellular matrix and increase the protective effects of extracellular matrix. It might achieve its anti-tumor effect through effecting the invasive and metastatic capabilities of breast tumor cells.

The possible window of implantation for embryos in the first frozen embryo transplantation cycle: A retrospective analysis.

OBJECTIVE: This study aimed to investigate the duration of progesterone (P) therapy on clinical pregnancy rates as measured by the window of implantation (WOI) in the first cycle of frozen embryo transplantation. METHODS: The study compared the pregnancy rates between 345 cleavage stage transfers and 348 blastocyte transfers of frozen embryos with modified natural cycles in patients from July 1, 2020, to November 30, 2020. Four different P durations were analyzed in the cleavage stage embryo transfer group, i.e., two, three, four, and five days. Five different P durations were analyzed in the blastocyst transfer group, i.e., three, four, five, six, and seven days. RESULTS: The baseline demographics and clinical characteristics of the cleavage stage embryos and blastocyst transfer groups were not comparable. The clinical pregnancy rates following the cleavage stage embryo transfer after two, three, four, and five-day P administration were 45.71%, 44.60%, 38.40%, and 30.43%, respectively (the difference among the subgroups was not significant). Following the blastocyst transfer, the clinical pregnancy rates after three, four, five, six, and seven-day P administration were 50.65%, 63.51%, 60.00%, 54.55%, and 61.54%, respectively (the difference among the subgroups was not significant). In contrast, these two transfer groups showed significantly different clinical pregnancy rates following four and five-day P exposure (P < 0.05). CONCLUSION: For cleavage-stage embryo transfer, the most effective WOI was found between days two and five of P administration. The effective WOI for blastocyst transfer was observed between days three and seven of P administrations.

Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement.

BACKGROUND: Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. METHODS: NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated. RESULTS: We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain. CONCLUSIONS: Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.

Neonatal programming by immunological challenge: effects on ovarian function in the adult rat.

Neonatal exposure to an immunological challenge (lipopolysaccharide, LPS) increases the activity of hypothalamo-pituitary-adrenal axis and sensitises the GNRH pulse generator to the inhibitory influence of stress in adult rats. We investigated the effects of neonatal exposure to LPS on various reproductive parameters during puberty and into adulthood in female rats. LPS (50 µg/kg, i.p.) or saline was administered on postnatal days 3 and 5. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 8-9 weeks of age. At 10 weeks of age, the ovaries were removed and the number of follicles was counted, together with the thickness of the theca interna of the largest antral follicles. Ovarian sympathetic nerve activity was assessed immunohistochemically by measurement of the levels of ovarian low-affinity receptor of nerve growth factor (p75NGFR). In rats exposed to LPS in early life, there was a significant delay in puberty and disruption of oestrous cyclicity immediately post puberty, which persisted into adulthood. The follicle reserve was decreased, the thickness of the theca interna increased and the expression profile of ovarian p75NGFR increased in the neonatal LPS-treated animals. These data suggest that exposure to LPS during early neonatal life can have long-term dysfunctional effects on the female reproductive system, which might involve, at least in part, increased ovarian sympathetic nerve activity.