Stress responses to bacterial and viral mimetics in polycystic ovary syndrome model rats.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.

Kisspeptin administration may promote precopulatory behavior in male rats independently or supplementally to testosterone and contribute to proceptive behavior in female partners, reducing mating failure.

Kisspeptin is a peptide that plays an important role through its effects on the hypothalamus-pituitary-gonadal (HPG) axis. It has also been implicated in sexual behavior. The present study investigated whether the relationship between kisspeptin and sexual behavior is independent of the HPG axis, i.e., testosterone. Sexual behavior was examined after the administration of kisspeptin to gonadally intact male rats and gonadectomized male rats that received testosterone supplementation. Other male rats were also observed for sexual behavior once a week from 2 to 5 weeks after gonadectomy and receiving kisspeptin for the sixth postoperative week. Sexual behavior in female rats serving as the partner for each male was also observed. Female rats were not administered kisspeptin in the present study. The results obtained showed that the administration of kisspeptin increased precopulatory behavior in gonadally intact male rats and gonadectomized male rats that received testosterone supplementation and proceptive behavior in their female partners. Precopulatory behavior in males and receptive behavior in females increased, while copulatory behavior in males and receptive behavior in females remained unchanged. Furthermore, the administration of kisspeptin increased precopulatory behavior in gonadectomized males, but did not affect receptive behavior in females. These results suggest that kisspeptin affected males independently and/or supplementally to testosterone, and also that changes in the presence of testosterone in males had an impact on proceptive behavior in their female partners. In conclusion, kisspeptin may involve an as-yet-unidentified neural pathway in sexual desire independently of the HPG axis.

Progesterone treatment reduces food intake and body weight in ovariectomized female rats.

While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.

Oncologic, fertility, and obstetric outcomes with MPA therapy in women with endometrial cancer and atypical endometrial hyperplasia.

AIM: Medroxyprogesterone acetate (MPA) is one of the treatments of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) to preserve the fertility. Efficacy of MPA therapy and fertility and obstetric outcomes after remission were evaluated in EC or AEH patients. METHODS: Among patients diagnosed with EC or AEH at Tokushima University Hospital between January 2002 and October 2020, we retrospectively analyzed patients, ages range from 26 to 40, who underwent conservative management using MPA (400-600 mg/day). RESULTS: In total, 19 patients underwent MPA therapy. The 18 (94%) patients achieved complete response (CR), and 1 (5%) patient achieved partial response (PR). Relapse occurred in 6 (32%) patients who had achieved CR. Of the patients who relapsed, 4 patients resumed MPA therapy and were in remission. Among 19 patients, 13 patients attempted pregnancy after CR. All of them underwent ovulation induction or assisted reproductive technology. As a result, 20 pregnancies in 10 (77%) patients and 12 live births in 9 (69%) patients were achieved. Rate of spontaneous abortion was 35% (7/20). CONCLUSIONS: MPA therapy can produce a high remission rate, and be considered an effective treatment for patients who wish fertility preservation. Around 70% patients who attempt to pregnancy can have at least one baby by infertility treatments. Because recurrence rate after MPA therapy is high, it may be desirable to aim for early pregnancy by active intervention.

Long- and Short-Term Trends in Outpatient Attendance by Speciality in Japan: A Joinpoint Regression Analysis in the Context of the COVID-19 Pandemic.

The COVID-19 pandemic resulted in a decline in outpatient attendance. Therefore, this study aimed to clarify long- and short-term clinic attendance trends by speciality in Japan between 2009 and 2021. A retrospective observational study of Japan's claims between 2009 and 2021 was conducted using the Estimated Medical Expenses Database. The number of monthly outpatient claims in clinics was used as a proxy indicator for monthly outpatient attendance, and specialities were categorised into internal medicine, paediatrics, surgery, orthopaedics, dermatology, obstetrics and gynaecology, ophthalmology, otolaryngology, and dentistry. The annually summarised age-standardised proportions and the percentage of change were calculated. Joinpoint regression analysis was used to evaluate long-term secular trends. The data set included 4,975,464,894 outpatient claims. A long-term statistically significant decrease was observed in outpatient attendance in internal medicine, paediatrics, surgery, ophthalmology, and otolaryngology during the pandemic. From March 2020 to December 2021, which includes the COVID-19 pandemic period, outpatient attendance in paediatrics, surgery, and otolaryngology decreased in all months compared with that of the corresponding months in 2019. For some specialities, the impact of the pandemic was substantial, even in the context of long-term trends. Speciality-specific preparedness is required to ensure essential outpatient services in future public health emergencies.

Age-Dependent Changes in the Effects of Androgens on Female Metabolic and Body Weight Regulation Systems in Humans and Laboratory Animals.

In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and ß-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.

Effects of activation with a Ca ionophore and roscovitine on the development of human oocytes that failed to fertilize after ICSI.

OBJECTIVE: The effects of oocyte activation with a Ca ionophore and roscovitine (Ca+R), a selective inhibitor of M-phase promoting factor, on unfertilized oocytes after intracytoplasmic sperm injection (ICSI) or testicular sperm extraction (TESE)-ICSI were evaluated. METHOD: Oocytes without pronuclei at 18 hours after ICSI were judged to be unfertilized and were exposed to the Ca ionophore A23187 (5 ?M) with or without roscovitine (50 ?M). The activation rate was measured 3, 7, and 18 hours later. Oocytes with two polar bodies and two pronuclei with a sperm tail were judged to have been activated. RESULTS: At 18 hours, the activation rates in the control, Ca ionophore, and Ca+R groups were 3.5% (4/112), 26.9% (7/26), and 32.1% (17/53), respectively. The activation rate of the Ca+R group was significantly higher than that of the control and similar to that of the Ca ionophore group. Among the oocytes that remained unfertilized after TESE-ICSI, the activation rates of the Ca ionophore and Ca+R groups were 22.2% (2/9) and 43.8% (7/16), respectively. CONCLUSIONS: Sequential treatment with an Ca ionophore and roscovitine activates oocytes that remain unfertilized after ICSI. In TESE-ICSI, the activation rate tended to be increased by the co-administration of roscovitine with a Ca ionophore. J. Med. Invest. 70 : 321-324, August, 2023.

Epidemiologic trends and distributions of imported infectious diseases among travelers to Japan before and during the COVID-19 pandemic, 2016 to 2021: a descriptive study.

BACKGROUND: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the COVID-19 pandemic. This article aimed to describe those among travelers to Japan. METHODS: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020). RESULTS: A total of 3524 imported infectious disease cases were diagnosed during the study period, including 3439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95%CI, 41.5-78.7), malaria (21.7; 10.5-33.0), and typhoid fever (9.3; 1.9-16.8). CONCLUSION: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance.

New discoveries on the interaction between testosterone and oxytocin in male rats - Testosterone-mediated effects of oxytocin in the prevention of obesity.

Sex steroid hormones are important for the maintenance of metabolism in both sexes. Oxytocin (OT) is a neuropeptide that is synthesized in hypothalamic regions, secreted from the posterior lobe of the pituitary gland, and is involved in the control of appetite, body weight, and metabolism. Estrogen and OT both play a role in the metabolism of nutrients, and OT has potential in the prevention of obesity. However, the relationship between testosterone and OT remains unclear. Therefore, the present study investigated the relationship between testosterone and OT in hypogonadal male rats and male rats receiving testosterone replacement therapy. The results obtained showed that testosterone increased serum OT levels and promoted the secretion of adiponectin from visceral fat, and reduced body fat directly and/or indirectly through OT and adiponectin. Testosterone also increased the expression of OT receptors in the hypothalamus to increase sensitivity to OT, and perhaps because of this, OT administration had the effect of reducing food intake and body weight gain in both normal and castrated rats, and this effect was stronger in normal rats. In other words, the preventative effects of OT on obesity may be synergistic with testosterone. Collectively, the present results indicate that testosterone exerts indirect effects to prevent obesity and atherosclerosis through OT and adiponectin. In conclusion, testosterone replacement therapy is useful for preventing obesity caused by hypogonadism, and OT has potential in supportive medicine to prevent obesity and adult diseases.

Changes in Serum Oxytocin Levels under Physiological and Supraphysiological Gonadal Steroid Hormone Conditions in Women of Reproductive Age: A Preliminary Study.

Oxytocin (OT) affects many behavioral, psychological, and physiological functions, including appetite and body weight regulation. Central and peripheral OT levels are markedly affected by gonadal steroids, especially estrogen, and the anorectic effects of estrogen are partially mediated by OT in rodents. In this study, the relationship between the estrogen milieu and serum OT levels was evaluated in women of reproductive age under physiological (n = 9) and supraphysiological estrogenic conditions (n = 7). Consequently, it was found that serum OT levels were increased in physiological (the ovulatory phase) and supraphysiological (on the day of the human chorionic gonadotropin trigger in an ovarian stimulation cycle) estrogenic conditions, and that serum OT levels were positively correlated with serum estradiol levels. On the other hand, serum OT levels were negatively correlated with serum progesterone levels, and there was no correlation between serum and follicular OT levels. These results suggest that OT levels may be positively and negatively regulated by estrogen and progesterone, respectively, in humans. However, the physiological roles of these actions of gonadal steroids on OT remain unclear.

Effects of undernutrition and low energy availability on reproductive functions and their underlying neuroendocrine mechanisms.

It has been well established that undernutrition and low energy availability disturb female reproductive functions in humans and many animal species. These reproductive dysfunctions are mainly caused by alterations of some hypothalamic factors, and consequent reduction of gonadotrophin-releasing hormone (GnRH) secretion. Evidence from literature suggests that increased activity of orexigenic factors and decreased activity of anorexigenic/satiety-related factors in undernourished conditions attenuate GnRH secretion in an integrated manner. Likewise, the activity of kisspeptin neurons, which is a potent stimulator of GnRH, is also reduced in undernourished conditions. In addition, it has been suggested that gonadotrophin-inhibitory hormone, which has anti-GnRH and gonadotrophic effects, may be involved in reproductive dysfunctions under several kinds of stress conditions. It should be remembered that these alterations, i.e., promotion of feeding behavior and temporary suppression of reproductive functions, are induced to prioritize the survival of individual over that of species, and that improvements in metabolic and nutritional conditions should be considered with the highest priority.

Is a freeze-all strategy necessary for all embryo transfers†: Fresh embryo transfer without progesterone elevation results in an equivalent pregnancy rate to cryopreserved embryo transfer.

Objectives : It has been suggested that the clinical outcomes of frozen-thawed embryo transfer (ET) are superior to those of fresh embryo transfer. We examined whether a freeze-all strategy is necessary for all embryo transfers, and, if not, to evaluate the conditions in which the pregnancy rates of fresh embryo transfer and frozen-thawed ET did not differ. Methods : Patients who underwent blastocyst transfer at Tokushima University Hospital between 2008 and 2019 were enrolled. The clinical outcomes and clinical characteristics of 1,022 patients that underwent fresh embryo transfer and 1,728 patients that underwent frozen-thawed ET were examined retrospectively. We considered the factors that influenced the pregnancy outcomes of fresh embryo transfer. Results : The frozen-thawed ET group exhibited significantly higher pregnancy, live-birth, and miscarriage rates than the fresh embryo transfer group. In the fresh embryo transfer group, a high progesterone level on the day of the human chorionic gonadotropin (hCG) trigger and lower grade embryos were risk factors for a low pregnancy rate. However, in the cases in which the progesterone level was < 1.0 ng / mL the pregnancy rate was equal to that of frozen-thawed ET. Conclusions : A freeze-all strategy is not necessary for embryo transfers, but should be employed in cases involving pre-ovulatory progesterone elevation. J. Med. Invest. 69 : 224-229, August, 2022.

Trends in dental visits during the state of emergency for COVID-19 in Japan: a retrospective observational study.

OBJECTIVES: To determine national medium-term trends in dental visits during three COVID-19 emergency declaration periods in Japan and to analyse how these trends varied according to prefectural emergency measures and COVID-19 incidence. DESIGN AND SETTING: A retrospective observational study of Japan's dental claims from January 2017 to December 2021. DATA SOURCES: Data from a monthly report by the Health Insurance Claims Review and Reimbursement Services (HICRRS) in Japan. HICRRS handles the claims of employer-based health insurance. DATA ANALYSIS: We determined the number of monthly dental claims nationwide from January 2017 to December 2021 and the percentage change in the number of monthly dental claims based on the difference in the COVID-19 alert level between the three emergency declaration periods in 2020-2021 and the corresponding periods in 2019. Results were analysed using descriptive statistics, multiple regression model, graphical figures, and narrative synthesis. OUTCOME MEASURES: The main outcome was the change in the number of dental visits between the emergency declaration periods in 2020-2021 and the corresponding periods in 2019. We also assessed the difference in the number of dental visits based on the COVID-19 alert level. RESULTS: The data set included a total of 736 946 088 dental claims. Until the end of 2021, the greatest decrease in monthly dental claims was in April 2020, which was 22.3% lower than that in April 2019. As indicated by the coefficient in the regression model, the percentage change in monthly dental claims decreased by 5.01% (95% CI -8.27 to -1.74) depending on the difference between the prefectures designated as being under special precautions and other prefectures. CONCLUSIONS: The decrease in dental visits was greater during the first state of emergency, ie, April-May 2020, and in prefectures designated as being under special precautions. Further efforts to promote appropriate dental visits at different alert levels are necessary.

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Neuroendocrine mechanisms of reproductive dysfunctions in undernourished condition.

It is well known that undernourished conditions disturb female reproductive functions in many species, including humans. These alterations are mainly caused by a reduction in gonadotrophin-releasing hormone (GnRH) secretion from the hypothalamus. Evidence from the literature suggests that some hypothalamic factors play pivotal roles in the coordination of reproductive functions and energy homeostasis in response to environmental cues and internal nutritional status. Generally, anorexigenic/satiety-related factors, such as leptin, alpha-melanocyte-stimulating hormone, and proopiomelanocortin, promote GnRH secretion, whereas orexigenic factors, such as neuropeptide Y, agouti-related protein, orexin, and ghrelin, attenuate GnRH secretion. Conversely, gonadotrophin-inhibitory hormone, which exerts anti-GnRH and gonadotrophic effects, promotes feeding behavior in many species. In addition, the activity of kisspeptin, which is a potent stimulator of GnRH, is reduced by undernourished conditions. Under normal nutritional conditions, these factors are coordinated to maintain both feeding behavior and reproductive functions. However, in undernourished conditions their activity levels are markedly altered to promote feeding behavior and temporarily suppress reproductive functions, in order to prioritize the survival of the individual over that of the species.

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes.

BACKGROUND: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. PURPOSE: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. METHODS: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). RESULTS: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. CONCLUSIONS: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research.

[Dental care behavior and related factors during the COVID-19 state of emergency in Japan].

Objectives　In response to the spread of SARS-CoV-2, a state of emergency was declared in Japan on April 7, 2020, and in the same month, Japan's Ministry of Health, Labor, and Welfare informed dentists of the need to postpone non-emergency dental care. The purpose of this study was to identify the patients who refrained from dental care during the state of emergency in April 2020, and to clarify their personal characteristics.Methods　A total of 1,335 patients who visited 28 dental clinics in Saitama in September 2020 completed survey questionnaires; of these, 1,227 valid responses were received. Among those who sought dental care under the state of emergency, those who did not visit a dental clinic comprised the "refrained group" and those who visited the dental clinics comprised the "visited group".Results　Multivariate logistic regression analysis showed that the odds ratios for the "refrained group" were 1.69 (95%Cl: 1.12-2.55) for females, 2.91 (95%Cl: 1.88-4.49) for those younger than 65 years, 1.71 (95%Cl: 1.04-2.82) for those that visited the dental clinic less than once a month, and 7.12 (95%Cl: 4.56-11.11) for those who did not have an appointment during the state of emergency.Conclusion　In conclusion, 35% of patients in this study refrained from visiting the dental clinic during the state of emergency. The related factors for refraining from dental care were being females, middle-aged (<65 years), visiting the dental clinic less than once a month, and not having an appointment during the COVID-19 state of emergency.

Effects of gonadal status and the estrogen milieu on hypothalamic oxytocin gene expression and serum oxytocin levels in female rats.

Oxytocin (OT) and its receptor (OTR) play various roles in the central and peripheral regulation of appetite and body weight. Previously, we have shown that the administration of OT markedly decreased appetite and body weight gain in ovariectomized (OVX) obese rats. In addition, recent studies have shown that the endogenous OT system is also affected by endogenous or exogenous estrogen. In this study, we showed that ovariectomy decreased rats' hypothalamic OT/OTR mRNA and serum OT levels, but did not affect their visceral fat OTR mRNA levels. The chronic administration of estradiol (E2) abrogated these ovariectomy-induced changes; i.e., it increased the rats' hypothalamic OT/OTR mRNA and serum OT levels, and may be associated with reductions in food intake and body weight gain. In addition, acute E2 administration increased the rats' hypothalamic OTR mRNA and serum OT levels, but did not affect their hypothalamic OT mRNA levels. Taken together, these results suggest that endogenous OT and/or OTR expression might be positively regulated by E2 and that the suppressive effects of E2 on appetite and body weight gain might be mediated, at least in part, by the OT system. Thus, we consider that OT might be a target hormone to pursue subsequent interventions of menopause for menopause-induced metabolic disorders.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020.

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

The reduction in sexual behavior of adult female rats exposed to immune stress in the neonatal period is associated with reduced hypothalamic progesterone receptor expression.

PURPOSE: We examined the mechanism by which neonatal immune stress reduces the sexual behavior of female rats in adulthood. METHODS: Neonatal female rats were randomly divided into 3 groups: control (n = 11), postnatal day 10 lipopolysaccharide (PND10LPS) (n = 23), and PND25LPS (n = 11) groups, which received intraperitoneal injections of LPS (100 µg/kg) or saline on PND10 and 25. Daily inspections of the vaginal opening (VO) were performed from PND27 to PND37. Thereafter, the frequency of estrus was assessed for 15 days. Female rats (at 11-12 weeks of age) were placed in a cage with male rats, and their sexual behavior was monitored for 30 min. The hypothalamic mRNA expression levels of factors related to sexual behavior were examined via real-time PCR. RESULTS: VO occurred later and the frequency of estrus was lower in the PND10LPS group compared to the control group. The number of lordosis behaviors and the total number of mounts performed by male partners were lower in the PND10LPS and PND25LPS groups than in the control group. Acceptability: The lordosis quotient and lordosis rating were lower in the PND10LPS group than in the control group. Proceptive behavior: the number of ear wiggling events was lower in the PND10LPS group than in the other groups, and the number of hops/darts was lower in the PND10LPS group than in the control group. The hypothalamic mRNA expression level of progesterone receptors (PR)A + B was lower in the PND10LPS group than in the control group, and the hypothalamic PRB mRNA expression level was lower in the PND10LPS and PND25LPS groups than in the control group. CONCLUSION: Neonatal immune stress impeded sexual behavior and hypothalamic PR mRNA expression in female rats. Decreased progesterone activity in the hypothalamus might explain the reduction in sexual behavior seen in these rats.