Gestational bisphenol A exposure advances puberty onset in female offspring: Critical time window identification.

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

Can maternal exposure to tamoxifen compromise sperm and behavioural parameters of male rat offspring?

Tamoxifen, a selective non-steroidal estrogen receptor modulator, is the standard adjuvant endocrine treatment for breast cancer. Since information on the risk of using tamoxifen during pregnancy is still scarce, this study evaluated whether the in utero and lactational treatment with this drug could compromise reproductive and behavioural parameters in male offspring. Pregnant Wistar rats were exposed to three doses of tamoxifen (0.12; 0.6; 3 µg/kg), by gavage, from gestational day 15 to lactational day 20. Tamoxifen exposure did not alter the anogenital distance in the male offspring; however, there was a significant increase in the body weight in the 0.12 µg/kg dose and a decrease in the 0.6 µg/kg dose. The male offspring treated with the highest dose exhibited a delay in the onset of puberty, evidenced by an increase in the age of preputial separation. Regarding sperm parameters, there was an increase in the sperm count in the cauda epididymis in the intermediate and highest dose groups, in addition to an increase in the number of static sperm and a decrease in the progressive sperm in the same groups. Moreover, an increase in the number of hyperplasia of the epithelial clear cells was observed in the epididymis. In conclusion, the present study demonstrated that maternal exposure to tamoxifen compromised the installation of puberty of the male offspring and the maturation of the epididymis, affecting sperm storage and motility in the adult life.

Fatty acid compositions of immature and mature testis are differently responsive to dietary docosahexasenoic acid during development in rats exposed to prenatal ethanol.

BACKGROUND: Ethanol (EtOH) exposure impairs, but docosahexaenoic acid (DHA) supports testis functions. This study investigated whether dietary DHA and prenatal EtOH exposure affected fatty acid profiles equally in immature and mature testis during developmental stages. METHODS: Female rats were exposed to ± EtOH (3g/kg BW, twice a day via gavage) throughout pregnancy, while consuming a diet supplemented ± DHA (1.4%, w/w). Pups were continued on their mother's diet after weaning with testes collected for fatty acid analysis at different stages of reproductive development, at gestational day 20 (GD20) and postnatal day (PD) 4, 21, 49, and 90, to present fetal, neonatal, weaning, prepubertal and adult stages, respectively. RESULTS: Regardless of EtOH exposure, dietary DHA significantly increased in testis DHA at all ages, with testis at weaning and prepuberty being more responsive to the diet (p<0.0002). Immature testis at GD20 and PD4 contained more DHA than n-6 docosapentaenoic acid (n-6 DPA) compared to mature testis while being well responsive to the maternal DHA diet through gestation and lactation. The level of n-6 very long chain fatty acids and (VLCFA) and n-6 DPA, distinctively increased from weaning and prepuberty, respectively, and were not reduced by the DHA diet at prepuberty and adulthood. Prenatal EtOH minimally affected testis fatty acids during development. CONCLUSION: Immature and mature testis responds differently to dietary DHA. The age around sexual maturity might be a critical time for dietary intervention as testis was more responsive to diet at this time point. The increase in DPA and n-6 VLCFA in matured testis while not affected by dietary DHA, indicates their critical roles in male reproductive function in rodents.

Global cerebral ischemia in adolescent male Long Evans rats: Effects of vanillic acid supplementation on stress response, emotionality, and visuospatial memory.

The developmental period is critical in delineating plastic response to internal and external events. However, neurobehavioural effects of global cerebral ischemia (GCI) in the maturing brain remain largely unknown. This study characterised the effects of GCI experienced at puberty on adulthood (1) hippocampus CA1 neuronal damage, (2) cognitive and emotional impairments, and (3) glucocorticoid receptor (GR) expression. Effects of adolescent exposure to the phenol vanillic acid (VA) on post-ischemic outcomes were also determined. Male Long Evans rats (n = 35) were supplemented for 21 consecutive days (postnatal days 33-53) with VA (91 mg/kg) or nut paste vehicle (control) prior to a 10-min GCI or sham surgery. As adults, rats were tested in the Open Field Test (OFT), Elevated-Plus Maze (EPM), and Barnes Maze (BM). GR expression was determined in the basolateral amygdala (BLA), CA1, and paraventricular nucleus (PVN), and brain injury assessed via CA1 neuronal density. Adolescent GCI exposure induced extensive hippocampal CA1 injury, which was not prevented by VA supplementation. Behaviourally, GCI increased EPM exploration while having no impact on spatial memory. VA intake increased OFT peripheral exploration. Notably, while no delayed changes in CA1 and PVN GR immunoreactivity were noted, both treatments separately increased BLA GR expression when compared with sham-nut paste rats. Age at GCI occurrence plays a critical role on post-ischemic impairments. The observation of minimal functional impairments despite important CA1 neuronal damage supports use of compensatory mechanisms. Our findings also show daily VA supplementation during adolescence to have no protective effects on post-ischemic outcomes, contrasting adult intake.

Melatonin Administration Accelerates Puberty Onset in Mice by Promoting FSH Synthesis.

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days 10 mice at a dose of 15 mg/kg accelerated the puberty onset in mice. Mechanistically, there was no difference in physical growth and serum Leptin levels after melatonin administration. Meanwhile, the serum levels of reproductive hormones involved in hypothalamic-pituitary-ovarian axis, such as FSH and estrogen level in serum were increased. The mRNA levels of GnRH and GnRHr were not affected by melatonin, while the expressions of FSHß in pituitary and Cyp19a1 in ovary were significantly up-regulated. In addition, melatonin still promoted FSH synthesis after ovariectomy. Furthermore, the enhanced activity of ERK1/2 signaling verified that the expression of FSHß increased in pituitary. We confirmed that melatonin promoted the FSH synthesis in pituitary, thereby increased serum estrogen levels and ultimately accelerated puberty onset. However, these effects of melatonin may be pharmacological due to the high dose. This study would help us to understand the functions of melatonin in pubertal regulation comprehensively.

Effects of Talinum paniculatum (Jacq.) Gaertn. leaf extract on general toxicity and pubertal development of rats.

Talinum paniculatum (Jacq.) Gaertn. (Talinaceae), popularly known as "major gomes," is a Brazilian Cerrado plant used in traditional medicine and as a food source. Recent studies have demonstrated its diuretic effects. However, no studies have been performed on its effects on the reproductive system. Therefore, we aimed to investigate the effects of the ethanol-soluble fraction of T. paniculatum leaves (ESTP) on general toxicity and on the pubertal development of male and female Wistar rats. For this purpose, the uterotrophic and the pubertal assays were performed. In the uterotrophic test, female immature rats were treated for three consecutive days with 30, 100, or 300 mg/kg of ESTP. Uterus without luminal fluid was weighed and the relative weight calculated. For the pubertal assay, male and female immature rats were submitted to 30-day treatment with 30 or 300 mg/kg of ESTP. Clinical signs of toxicity, biochemical, and histopathological parameters were evaluated. ESTP treatment did not promote estrogenic effects in female rats. In the pubertal test, no daily signs of toxicity or weight loss were observed. Moreover, ESTP did not affect the onset of vaginal opening and preputial separation and did not cause significant changes in biochemical parameters as well as in organ weight and histopathological analyses of animals.

Effects of dietary supplementation with algae, sunflower oil or soybean oil on folliculogenesis in the rabbit ovary during sexual maturation.

This study aimed to examine the effects of algae (rich in omega-3 fatty acids), sunflower oil (rich in omega-6 fatty acids) and soybean oil (rich in omega-6 fatty acids) on the entire folliculogenesis in juvenile and sexually mature rabbits. After weaning, rabbits were randomly divided into four experimental groups of 14 animals each. Control animals received non-supplemented pellets, while in the other groups, the pellets contained 1% marine algae, 3% sunflower oil or 3% soybean oil. Animals from each group were slaughtered at 12 weeks of age (n = 7 per group) or at 18 weeks of age (n = 7 per group). The ovaries were harvested and fixed for hematoxylin-eosin staining, immunohistochemical localization of PCNA and TUNEL assay. Algae-enriched diet markedly decreased the number of primordial and primary follicles, while addition of sunflower oil reduced the number of primary follicles in 12-week-old rabbits. The number of antral follicles was higher following algae supplementation, but lower after addition of soybean oil in that age group. Proliferating index was decreased following supplementation with algae and soybean oil in juvenile rabbits, whereas it was increased after addition of algae and decreased following vegetable oils in mature ones. Dietary PUFAs did not impact apoptosis in the rabbit ovary of both age groups. The obtained results suggest that PUFA-enriched diet regulate either early folliculogenesis or antral follicle development in rabbits that might influence reproductive performance as a consequence. It appears that observed effects are attributed to sexual maturity.

Supplementation frequency and amount modulate postweaning growth and reproductive performance of Bos indicus-influenced beef heifers.

This 2-yr study evaluated the growth and puberty attainment of Bos indicus-influenced beef heifers offered 2 different postweaning concentrate supplementation amounts and delivery frequencies. On day 0 of each year, 64 Brangus crossbred heifers were stratified by initial body weight (BW) and age (mean = 244 ± 22 kg; 314 ± 17 d) and assigned into 1 of 16 bahiagrass pastures (4 heifers/pasture/yr). Treatments were randomly assigned to pastures in a 2 × 2 factorial design (4 pastures/treatment/yr) and consisted of concentrate dry matter (DM) supplementation at 1.25% or 1.75% of BW which were offered either daily (7×) or 3 times weekly (3×) for 168 d. On day 56 of each year, heifers were assigned to an estrus synchronization protocol consisting of intravaginal controlled internal drug release (CIDR) insertion on day 56, CIDR removal on day 70, i.m. injection of 25 mg of prostaglandin F2α (PGF2α) on day 86, and i.m. injection of 100 µg of gonadotropin-releasing hormone and timed-AI at 66 h after PGF2α injection (day 89). Heifers were exposed to Angus bulls from day 89 to 168 (1 bull/pasture). Pregnancy diagnosis was assessed on day 213 of each year. Supplementation amount × frequency effects were not detected (P ≥ 0.12) for any variable, except for plasma concentrations of glucose (P = 0.10) and urea nitrogen (PUN; P = 0.01). Herbage mass, herbage allowance, and nutritive value did not differ (P ≥ 0.12) among treatments. Increasing supplementation DM amount from 1.25% to 1.75% of BW increased (P ≤ 0.05) plasma concentrations of insulin-like growth factor 1 (IGF-1), overall average daily gain (ADG), final BW, percentage of pubertal heifers on day 89, pregnancy and calving percentages, and percentage of heifers calving within the first 21 d of the calving season. However, reducing the supplementation frequency from daily to 3× weekly, regardless of supplementation amount, did not impact overall pregnancy and calving percentages (P ≥ 0.42), but caused (P ≤ 0.05) fluctuations in plasma concentrations of insulin and IGF-1 and decreased (P ≤ 0.03) overall ADG, final BW, puberty attainment on days 56, 89, and 168, and percentage of heifers calving during the first 21 d of the calving season. Hence, increasing the supplement DM amount did not prevent the negative effects of reducing the frequency of supplementation (3× vs. 7× weekly) on growth and reproduction of replacement Bos indicus-influenced beef heifers.

Effects of dietary fatty acids on the social life of male Guinea pigs from adolescence to adulthood.

Dietary intake of polyunsaturated fatty acids (PUFAs) or saturated fatty acids (SFAs) differently modulates neurophysiological and behavioral functions in response to altered hypothalamic-pituitary-adrenal (HPA)-axis activity and an individual's development. In this context, an individual's social environment, including social interactions and social hierarchies, is closely related to hormone concentrations and possibly interacts with dietary fatty acid effects. We investigated if dietary supplementation with walnut oil (high in PUFAs) and coconut fat (high in SFAs), compared to a control group, affects body mass gain, cortisol and testosterone concentrations, plasma fatty acids, and social behavior in male domestic guinea pigs from adolescence to adulthood. For analyses of cortisol and testosterone concentrations, social interactions were included as covariates in order to consider effects of social behavior on hormone concentrations. Our results revealed that SFAs increased escalated conflicts like fights and stimulated cortisol and testosterone concentrations, which limited body mass gain and first-year survival. PUFAs did not remarkably affect social behavior and hormone concentrations, but enabled the strongest body mass gain, which probably resulted from an energetic advantage. Neither sociopositive nor agonistic behaviors explained age-specific differences in hormone concentrations between groups. However, a high number of subdominant individuals and lower testosterone concentrations were related to increased cortisol concentrations in adult PUFA males. Our findings demonstrate the importance of dietary fatty acids regarding behavioral and endocrine developmental processes and adaptations to the social environment by modulating HPA-axis function and body homeostasis.

Neonatal exposure to bisphenol A advances pubertal development in female rats.

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague-Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg-1 ·day-1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg-1 ·day-1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg-1 ·day-1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg-1 ·day-1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg-1 ·day-1 , neonatal exposure to BPA may affect pubertal development in a dose-dependent manner.

Justicia flava Leaves Exert Mild Estrogenic Activity in Mouse Models of Uterotrophic and Reproductive Cycle Investigations.

This study aimed to assess and determine the estrogenic activity of the leaf extract of Justicia flava (JF) in mice, which may interfere with its therapeutic use in female reproduction. The uterotrophic assay (UTA) utilizing 20 days old female mice and the reproductive cycle assay (RCA) utilizing adult female mice were used in this study. All administrations were performed orally. Reproductive organ and blood samples were collected the day after last administration of JF for histology and hormone analysis. Other parameters such as organ weight, temperature, body weight, and reproductive cycles were analyzed. Our study showed that for UTA, JF increased uterine weights slightly, which were nonsignificant but more pronounced at the highest dose of 1000 mg/kg. JF did not induce vaginal opening, which is a sign of puberty onset. JF also had minimal effect on organ morphology and caused a slight increase in serum estrogen. For RCA, JF did not significantly alter body weight and temperature although an upward trend in temperature was observed. JF did not disrupt cycling significantly (P > .005) compared with estrogen (the positive control drug used). JF also did not significantly alter uterus morphology except at 1000 mg/kg where some increase in the number of glands and cell activity were observed. JF has mild estrogenic activity and will not interfere with reproductive functions at lower doses (10-100 mg/kg) during therapy, but high doses (up to 1000 mg/kg and above) may cause some alterations. Our data, therefore, suggest that JF is a useful candidate in the management of female reproductive health issues at lower doses.

Serotonin type-3 receptors differentially modulate anxiety and aggression during withdrawal from adolescent anabolic steroid exposure.

Male Syrian hamsters (Mesocricetus auratus) administered anabolic/androgenic steroids during adolescent development display increased aggression and decreased anxious behavior during the adolescent exposure period. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts and hamsters exhibit decreased aggression and increased anxious behavior. This study investigated the hypothesis that alterations in anterior hypothalamic signaling through serotonin type-3 receptors modulate the behavioral shift between adolescent anabolic/androgenic steroid-induced aggressive and anxious behaviors during the withdrawal period. To test this, hamsters were administered anabolic/androgenic steroids during adolescence then withdrawn from drug exposure for 21 days and tested for aggressive and anxious behaviors following direct pharmacological manipulation of serotonin type-3 receptor signaling within the latero-anterior hypothalamus. Blockade of latero-anterior hypothalamic serotonin type-3 receptors both increased aggression and decreased anxious behavior in steroid-treated hamsters, effectively reversing the pattern of behavioral responding normally observed during anabolic/androgenic steroid withdrawal. These findings suggest that the state of serotonin neural signaling within the latero-anterior hypothalamus plays an important role in behavioral shifting between aggressive and anxious behaviors following adolescent exposure to anabolic/androgenic steroids.

Evaluation of Brassica carinata meal as a protein supplement for growing beef heifers1,2.

Brassica carinata is a new oilseed crop in Florida with the potential of producing high-quality jet biofuel. A high-protein meal (~40% crude protein; CP) is obtained as a byproduct of oil extraction; however, limited research is available on the utilization of this meal as a protein supplement for beef cattle. A generalized randomized block design was used to evaluate the effects of supplementation with B. carinata meal pellets on performance and attainment of puberty in growing beef heifers consuming bermudagrass hay (Cynodon dactylon) ad libitum. Sixty-four Angus crossbred heifers (240 ± 39 kg initial body weight; BW) were stratified and blocked (2 blocks: light and heavy) by initial BW and randomly allocated into 18 pens over 2 consecutive years (10 in year 1 and 8 in year 2). Within block, pens were randomly assigned to 1 of 2 treatments: 0 (CTL) or 0.3% of BW/d (as fed) of B. carinata meal pellets (BCM). Blood samples and BW were collected weekly for 70 d, before daily supplementation. Data were analyzed using PROC MIXED of SAS with repeated measures. Model included the fixed effects of treatment, day, treatment × day interactions, block, and block × treatment interactions, with the random effect of year. Plasma was analyzed for concentrations of progesterone, triiodothyronine (T3), thyroxine (T4), ceruloplasmin (Cp), and haptoglobin (Hp). An effect of treatment was observed (P ˂ 0.01) for ADG between CTL (0.14 kg) and BCM (0.42 kg). There was no treatment or block (P > 0.05) effect for concentrations of T3, T4, or Hp; however, there was an effect of day (P < 0.01) for T3, T4, and Cp. An effect of treatment (P ˂ 0.01) was observed for Cp, with CTL having greater concentrations compared with BCM. Time to attainment of puberty did not differ (P = 0.93) between treatments. Feeding B. carinata meal as a protein supplement at 0.3% of BW/d is a viable option for increasing ADG of growing beef heifers, without affecting attainment of puberty, thyroid hormone status, or eliciting an acute phase response.

Dietary Intake of Selenium in Relation to Pubertal Development in Mexican Children.

Alterations in pubertal timing have been associated with long-term health outcomes. While a few reports have shown that dietary intake of selenium is associated with fertility and testosterone levels in men, no human studies have considered the association between selenium and pubertal development in children. We examined the cross-sectional association of childhood dietary intake of selenium with pubertal development among 274 girls and 245 boys aged 10-18 years in Mexico City. Multiple logistic and ordinal regression models were used to capture the association between energy-adjusted selenium intake (below Recommended Dietary Allowance (RDA) vs. above RDA) and stages of sexual maturity in children, adjusted for covariates. We found that boys with consumption of selenium below the RDA had lower odds of a higher stage for pubic hair growth (odds ratio (OR) = 0.51, 95% confidence interval (95% CI): 0.27-0.97) and genital development (OR = 0.53, 95% CI: 0.28-0.99) as well as a lower probability of having matured testicular volume (OR = 0.37, 95% CI: 0.15-0.88) compared with boys who had adequate daily dietary intake of selenium (above RDA). No associations were found in girls. According to our results, it is possible that inadequate consumption of selenium may be associated with later pubertal development in boys, suggesting a sex-specific pattern. Future work with a larger sample size and measures of selenium biomarkers is needed to confirm our findings and improve understanding of the role of this mineral in children's sexual development.

Effect of selenium supplementation on attainment of puberty in Saanen male goat kids.

The aim of the study was to evaluate the effect on selenium supplementation on attainment of puberty in Saanen male goat kids. Forty Saanen male goats kids were divided into two groups: selenium supplemented (n = 20) and control (n = 20). The treatment group received sodium selenite at a ninety days interval for an experimental period of 150 days. All experimental Saanen male goat kids were fed Lucerne hay deficient in selenium. The development of the reproductive functions of the male goat kids was monitored until puberty. At the age of 5.5 months motile spermatozoa were collected from 65% of the supplemented group compared to 35% of the control. At 140 days following supplementation the treated group showed significantly higher semen volume per ejaculate and improved semen quality in the form of improved spermatozoa motility and concentration and a decreased percentage of dead spermatozoa, spermatozoa abnormalities and acrosome damage compared to the control. Supplementation with selenium significantly (P < 0.05) improved body weight, testicular measurements and decreased age at puberty. Selenium supplementation also led to higher (P < 0.05) LH and testosterone concentrations. It is concluded that selenium supplementation hastened age at attainment of puberty to 5.5 months in male Saanen kids as the control group attained puberty at 6 months. It also improved semen quality and reproductive hormones concentration of Saanen kids.

Ovarian follicular development, hormonal and metabolic profile in prepubertal ewe lambs with moderate dietary restriction and lipid supplementation.

To evaluate the effects of moderate dietary restriction and lipid supplementation on ovarian follicular development, hormonal and metabolic profile, thirty-five prepuberal ewe lambs were blocked by body weight and randomly assigned to treatments: ALUS (control) - unsupplemented-diet ad libitum (3.5% ether extract, n = 9); R-US - intake restricted to 85% of the ALUS diet (n = 9); AL-LS - lipid-supplemented-diet ad libitum (9.8% ether extract, n = 8); R-LS - intake restricted to 85% of the ALLS diet (n = 9), from 95 ± 8 days of age until estrus or 7 months of age. Lipid supplementation did not reduce dry matter intake. Daily weight gain was greater in lambs fed ad libitum. Plasma glucose was greater in the RLS treatment group, while serum insulin was less with lipid supplementation. There was a treatment by age interaction on total cholesterol, HDL cholesterol and triglyceride serum concentrations. Estrus was detected in 43% of the animals and the overall ovulation rate was 60%. The number of follicles, diameter of the largest follicle, body weight, age and serum progesterone at puberty did not differ among treatment groups. The mean diameter of the largest follicle was greater in lambs having than in those not having ovulations and increased with age in both groups. There was an interaction between the effects of occurrence of ovulation and age on the number of follicles between 3 and 5 mm and > 5 mm. Lipid supplementation and dietary restriction altered the metabolic profile in ewe lambs with no concomitant changes in values for reproductive variables.

Estrogen imprinting compromises male sexual behavior and affects the number of androgen-receptor-expressing hypothalamic neurons†.

Neonatal exposure to high-dose 17ß-estradiol (E2) affects the morphology and physiology of sex and accessory sex organs in the long term. In this study, we examined the effects of E2 imprinting on male sexual behavior, fertility, and the number of androgen receptor (AR)-expressing cells in the hypothalamus. E2-treated males showed copulatory behavior represented by mounts and/or intromissions, demonstrating the preservation of aspects of male behavior. They had slightly increased latency for first intromission and a reduced number of ejaculations, associated with a 50% reduction in the fertility index. AR expression in the hypothalamus was assessed by RT-PCR, western blotting, and immunohistochemistry. Treated rats had a significantly lower ventral prostate (VP) weight, demonstrating the efficacy of the treatment. The AR mRNA and protein content in the hypothalamus of E2-treated animals was reduced to the levels of females. AR-expressing cell counts in the ventromedial, anterior medial preoptic, paraventricular nuclei, and preoptic areas were different from control males, and similar to those of females. In conclusion, E2 imprinting resulted not only in ill-developed sexual organs, but also affected sexual behavior, resulting in a female-type hypothalamus, at least with respect to the abundance of AR mRNA and protein and the number of AR-expressing cells in important regions/tracts.

Neonatal and juvenile exposure to perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS): Advance puberty onset and kisspeptin system disturbance in female rats.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are widespread and persistent chemicals in the environment, and limited data about their effects on puberty development are available. In order to explore the effects of neonatal and juvenile PFOA/PFOS exposure on puberty maturation, female rats were injected with PFOA or PFOS at 0.1, 1 and 10 mg/kg/day during postnatal day (PND) 1-5 or 26-30. The day of vaginal opening (VO) and first estrus were significantly advanced in 10 mg/kg PFOA, 1 and 10 mg/kg PFOS groups after neonatal and juvenile exposure. Besides, neonatal PFOA/PFOS exposure increased body weight and anogenital distance (AGD) in a non-dose-dependent manner. Estradiol and luteinizing hormone levels were also increased with more frequent occurrences of irregular estrous cycles in 0.1 and 1 mg/kg PFOA/PFOS exposure groups. Although no altered ovarian morphology was observed, follicles numbers were reduced in neonatal groups. Kiss1, Kiss1r and ERα mRNA expressions were downregulated after two periods' exposure in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. PFOA/PFOS exposure also suppressed kisspeptin fiber intensities, especially at the high dose. In conclusion, neonatal and juvenile are critical exposure periods, during which puberty maturation may be vulnerable to environmental exposure of PFOA/PFOS, and kisspeptin system plays a key role during these processes.

Neuropeptide Control of Puberty: Beyond Kisspeptins.

Puberty is a fundamental developmental event in the lifespan of any individual, when sexual and somatic maturation is completed, and reproductive capacity is achieved. While the tempo of puberty is under strong genetic determination, it is also modulated by a wide array of internal and environmental cues, including, prominently, nutritional and metabolic signals. In the last decade, our understanding of the neurohormonal basis of normal puberty and its perturbations has enlarged considerably. This is illustrated by the elucidation of the essential roles of kisspeptins, encoded by the Kiss1 gene, in the hypothalamic circuits controlling puberty. Moreover, other neuropeptide pathways, convergent with kisspeptin signaling, have been pointed out as important coregulators of pubertal timing. These include the cotransmitters of Kiss1 neurons in the arcuate nucleus (ARC), neurokinin B, and dynorphin, as well as melanocortins, produced by ARC neurons expressing proopiomelanocortin, which are endowed with key roles also in the control of metabolic homeostasis. This neuropeptide setup seemingly participates, in a coordinated manner, in transmitting the regulatory actions of metabolic cues on pubertal maturation. In this function, cellular metabolic sensors, such as the AMP-activated protein kinase, and the fuel-sensing deacetylase, SIRT1, have also been shown recently to contribute to the metabolic regulation of puberty. Altogether, elucidation of the physiological roles of these signals and regulatory circuits will help uncover the intimacies of the brain control of puberty, and its alterations in conditions of metabolic stress, ranging from subnutrition to obesity.

Effect of chronic melatonin supplementation during mid to late gestation on maternal uterine artery blood flow and subsequent development of male offspring in beef cattle.

The objective of the current study was to examine the effects of supplemental melatonin implants on uterine artery blood flow from mid to late gestation in beef cattle and subsequent development of their male offspring. Commercial beef heifers (n = 32) and cows (n = 25) were bred via artificial insemination and assigned to 1 of 2 groups supplemented with melatonin implants (MEL) or without (CON) at day 180, 210, and 240 of gestation. Uterine artery blood flow was determined using color Doppler ultrasonography. A subset of 12 crossbred heifers (n = 6 MEL; n = 6 CON) underwent Cesarean sections on day 243 ± 2 of gestation to allow for placentome collection. Maternal and fetal serum were collected to analyze melatonin concentrations. The remaining cattle were allowed to calve and at weaning (195 ± 2 d of age), bull calves (n = 15) were castrated and testicular tissue harvested for seminiferous tubule analysis. Heifer uterine artery blood flow was increased (P = 0.009) at day 240 of gestation in MEL compared with CON heifers. Cow uterine artery blood flow was increased (P = 0.003) in MEL compared with CON cows irrespective of gestational day. Maternal and fetal concentrations of melatonin were increased (P < 0.05) in MEL compared with CON heifers. The percent of placentome capillary area per mm2 was decreased (P = 0.019) in MEL compared with CON heifers, while cotyledonary ANGPT1 mRNA tended to increase (P = 0.095) in MEL compared with CON heifers. At weaning, body weight of male offspring and their scrotal circumference were increased (P < 0.05) in calves born to MEL compared with CON dams, while seminiferous tubule diameter and area were not different (P > 0.40) between treatments. In summary, melatonin supplementation increased uterine artery blood flow in mid to late gestating cattle, but this was not accompanied by an increase in fetal weight. Alterations in postnatal development of bulls, including increased body weight and scrotal circumference, warrants future investigations related to attainment of puberty and subsequent fertility of offspring born to melatonin supplemented dams.