Is bovine somatotropin an alternative strategy to overcome the detrimental effects of high-gain diets on prepubertal Holstein × Gyr heifers?

Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.

Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats.

We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

F-53B mediated ROS affects uterine development in rats during puberty by inducing apoptosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Prepubertal exposure to polycyclic aromatic hydrocarbons are associated with early pubertal development onset in boys: A longitudinal study.

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.

Chlorpyrifos impairs sperm parameters and number of Sertoli and Leydig cells in rats after exposure during the peripubertal period.

Chlorpyrifos is an organophosphate insecticide used to control pests in crops. Thus, humans are constantly exposed through ingestion of contaminated food or water, inhalation of contaminated air, and through the skin. The juvenile and peripubertal periods comprise a window of development of the reproductive system, sensitive to toxic agents. Considering the scarcity of data on exposure to the insecticide during these periods, the aim of this study was to evaluate the effects of chlorpyrifos on the testis during the juvenile and peripubertal periods. Thirty Wistar rats with an initial age of 25 days were distributed into 3 groups: control, which received corn oil (vehicle); CPS5, which received 5 mg/Kg b.w. of chlorpyrifos; and CPS15, which received 15 mg/Kg b.w. of chlorpyrifos. The groups were treated via gavage daily for 40 days and on the 41st experimental day, the animals were anesthetized and submitted to euthanasia to collect the organs. Blood was collected to obtain plasma and testosterone measurement. The testicles were removed, weighed and used for sperm count analyses, histopathological and morphometric analyzes and for oxidative stress analyses. Spermatozoa from the vas deferens were collected for analyzes of sperm morphology and acrosome integrity. The results showed that the two concentrations of chlorpyrifos caused a decrease in the number of Leydig and Sertoli cells and germ cells and increased the number of morphologically abnormal sperm and sperm with acrosomal damage. Furthermore, a decrease in lipid peroxidation was observed in the CPS5 and CPS15 groups, and a decrease in glutathione-S-transferase activity in the CPS5 group. We conclude that exposure to chlorpyrifos harms the daily production of sperm, as well as their quality, in addition to causing an imbalance in the oxidoreductive balance of the testicle.

Adolescence is a sensitive period for acrylamide-induced sex hormone disruption: Evidence from NHANES populations and experimental mice.

Acrylamide (AA) is widely contaminated in environment and diet. However, the association of AA and sex hormones has rarely been investigated, especially in adolescents, a period of particular susceptibility to sex hormone disruption. In this study, survey-weighted multivariate linear regression models were conducted to determine the association between AA Hb biomarkers [HbAA and glycidamide (HbGA)] and sex hormones [total testosterone (TT) and estradiol (E2)] in a total of 3268 subjects from National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves. Additionally, adult and pubertal mice were treated with AA to assess the effect of AA on sex hormones and to explore the potential mechanisms. Among all the subjects, significant negative patterns for HbGA and sex hormones were identified only in youths (6-19 years old), with the lowest ß being - 0.53 (95% CI: -0.80 to -0.26) for TT in males and - 0.58 (95% CI: -0.93 to -0.23) for E2 in females. Stratified analysis further revealed significant negative associations between HbGA and sex hormones in adolescents, with the lowest ß being - 0.58 (95% CI: -1.02 to -0.14) for TT in males and - 0.54 (95% CI: -1.03 to -0.04) for E2 in females, while there were no significant differences between children or late adolescents. In mice, the levels of TT and E2 were dramatically reduced in AA-treated pubertal mice but not in adult mice. AA disturbed the expression of genes in the hypothalamic-pituitary-gonadal (HPG) axis, induced apoptosis of hypothalamus-produced gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and reduced serum and hypothalamic GnRH levels in pubertal mice. Our study indicates AA could reduce TT and E2 levels by injuring GnRH neurons and disrupting the HPG axis in puberty, which manifested as severe endocrine disruption on adolescents. Our findings reinforce the idea that adolescence is a vulnerable stage in AA-induced sex hormone disruption.

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.

Reproductive Development of Male Rats Exposed In Utero to Stress and/or Sertraline.

Despite increased prescription of sertraline during pregnancy, little is known about its action on reproductive development. Therefore, this study aimed to investigate the impact that stress, associated or not with sertraline, causes on the reproductive development of male rats. Pregnant Wistar rats were divided into 4 groups (n = 16/group): CO-received filtered water; SE-received 20 mg/kg sertraline; ST-submitted to restraint stress and received filtered water; SS-submitted to restraint stress and received sertraline. The treatment was carried out from gestational days (GDs) 13-20. The animals were euthanized on GD 20 (n = 8/group), postnatal day (PND) 45 (n = 8/group), and PND 110 (n = 8/group). The testes and epididymis were analyzed histologically, and immunohistochemistry was performed on the testes by proliferating cell nuclear antigen (PCNA) and the Wilms tumor protein (Wt1). Sperm quality was also analyzed on PND 110. The evolution of body weight, anogenital distance (AGD), and puberty installation day were also verified. Statistical analysis: 2-way ANOVA or Kruskal-Wallis test (p ≤ .05). Fetal testes presented a large number of acidophilic cells in the sertraline-exposed groups. The SS group also showed a decrease in the nuclear volume of Leydig cells. This same group showed low expression of PCNA and Wt1, decreased weight of the testes and epididymis, lower AGD, and delayed puberty installation. The adulthood groups exposed to sertraline presented alterations in sperm morphology and motility. The results demonstrated that prenatal exposure to sertraline compromises the development of the rat reproductive system.

Daily GnRH agonist treatment effectively delayed puberty in female rats without long-term effects on sexual behavior or estrous cyclicity.

The present study examined the long-term effects of suppressing puberty with a GnRH agonist on reproductive physiology and behavior in female rats. We have recently reported that administration of the GnRH agonist leuprolide acetate (25 µg/kg) daily between postnatal day (PD) 25-50 delayed puberty and disrupted the development of copulatory behavior and sexual motivation in male rats. However, pilot data from our lab suggest that this low dose of leuprolide acetate (25 µg/kg) was not high enough to significantly delay puberty in female rats. Therefore, we injected female Long-Evans rats with leuprolide acetate at a higher dose (50 µg/kg) or 0.9% sterile saline, daily , starting on PD 25 and ending on PD 50. Vaginal opening was monitored daily starting on PD 30 for signs of pubertal onset and first estrous cycle. In addition, we measured estrous cyclicity starting approximately 2 weeks after the last injection of leuprolide (∼PD 64). Immediately after monitoring estrous cyclicity, the female rats were mated on their first day in behavioral estrus using the partner-preference paradigm, with and without physical contact (PD 95-110). We found that this dose of leuprolide (50 µg/kg) significantly delayed puberty; however, neither estrous cyclicity nor sexual motivation was significantly affected by periadolescent exposure to leuprolide. Together with our findings in male rats, these results add to our understanding of the developmental effects of chemically suppressing puberty in rats.

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.

Combinational exposure to Bisphenol A and a high-fat diet causes trans-generational Malfunction of the female reproductive system in mice.

Bisphenol A (BPA) is a common endocrine disruptor and a high-fat diet (HFD) also affects fertility. However, little is known about the long-term consequences of simultaneous exposure to BPA and a HFD on reproductive health. Herein, we assessed the effects of maternal exposure to BPA in combination with a HFD on reproductive function in subsequent generations of female mice and evaluated its effects on the hypothalamic-pituitary-gonadal axis. We found that the combination of maternal exposure to BPA and a HFD led to increased urine BPA levels, precocious puberty, altered estrous cyclicity, decreased follicle numbers, and altered hypothalamic Kiss1 methylation status in F1 and F2 mice. Therefore, we demonstrated that maternal exposure to BPA in combination with a HFD exerts a trans-generational effect on female reproduction.

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.

Effects on Puberty of Nutrition-Mediated Endocrine Disruptors Employed in Agriculture.

Pesticide residues are largely found in daily consumed food because of their extensive use in farming and their long half-life, which prolongs their presence in the environment. Many of these pesticides act as endocrine-disrupting chemicals after pre- or postnatal exposure, significantly affecting, among other things, the time of puberty onset, progression, and completion. In humans, precocious or delayed puberty, and early or delayed sexual maturation, may entail several negative long-term health implications. In this review, we summarize the current evidence on the impact of endocrine-disrupting pesticides upon the timing of the landmarks of female and male puberty in both animals (vaginal opening, first estrus, and balanopreputial separation) and humans (thelarche, menarche, gonadarche). Moreover, we explore the possible mechanisms of action of the reviewed endocrine-disrupting pesticides on the human reproductive system. Access to safe, healthy, and nutritious food is fundamental for the maintenance of health and wellbeing. Eliminating the presence of hazardous chemicals in largely consumed food products may increase their nutritional value and be proven beneficial for overall health. Consequently, understanding the effects of human exposure to hazardous endocrine-disrupting pesticides, and legislating against their circulation, are of major importance for the protection of health in vulnerable populations, such as children and adolescents.

Exposure to Atrazine through gestation and lactation period led to impaired sexual maturation and subfertility in F1 male rats with congenital deformities in F2 progeny.

Several scientific reports suggest perturbed reproductive and developmental defects associated with environmental exposure to Atrazine (ATR). ATR has been associated with altered endocrine and reproductive functioning in-vivo exposed during the critical window of development. Thus, the present study investigates the effect of ATR exposure on F1-F2 male progeny exposed through gestation and lactation. F0 dams administered with ATR at doses 2, 10, 70, and 100 mg/kg b. wt/day from gestation day 6 to postnatal day 21. The F1 male rats were monitored for sexual maturation and subjected to fertility assessment on PND75. Delayed testicular descent was observed in 10, 70, and 100 mg/kg b. wt/day ATR dose with significantly lower serum testosterone, sperm count, and motility with testicular defects in F1 male. Expression of Androgen receptor (AR), Estrogen receptors (ER α and ER ß), StAR, Aromatase, and INSL-3 were upregulated at all doses indicating estrogenic/anti-androgenic activity of ATR. Fertility assessment revealed subfertility in F1 males with high (%) pre- and post-implantation loss at 10, 70, and 100 mg/kg b. wt/day dose as compared to control. Further, F2 fetuses exhibited congenital disabilities viz. decreased weight, crown-rump length, and anogenital distance with several other morphological deformities. To conclude, ATR exerted estrogenic and/or anti-androgenic activity with fetotoxic effects through the male germline.

Effects of PD-1 blockade on ovarian follicles in a prepubertal female mouse.

Immunotherapy has emerged at the forefront of cancer treatment. Checkpoint inhibitor pembrolizumab (KEYTRUDA), a chimeric antibody which targets programmed cell death protein 1 (PD-1), has been approved by the Food and Drug Administration (FDA) for use in pediatric patients with relapsed or refractory classical Hodgkin's lymphoma. However, there is currently no published data regarding the effects of pembrolizumab on the ovary of female pediatric patients. In this study, prepubertal immunocompetent and immunodeficient female mice were injected with pembrolizumab or anti-mouse PD-1 antibody. The number of primordial follicles significantly decreased post-injection of both pembrolizumab and anti-mouse PD-1 antibody in immunocompetent mice. However, no changes in follicle numbers were observed in immunodeficient nude mice. Superovulation test and vaginal opening experiments suggest that there is no difference in the number of cumulus-oocyte complexes (COCs) and the timing of puberty onset between the control and anti-mouse PD-1 antibody treatment groups, indicating that there is no effect on short-term fertility. Elevation of pro-inflammatory cytokine TNF-α following COX-2 upregulation was observed in the ovary. CD3+ T-cell infiltration was detected within some ovarian follicles and between stromal cells of the ovaries in mice following treatment with anti-mouse PD-1 antibody. Thus, PD-1 immune checkpoint blockade affects the ovarian reserve through a mechanism possibly involving inflammation following CD3+ T-cell infiltration.

Influence of hormonal imbalance on the integrity of seminiferous epithelium in the testes of adult rats chronically exposed to letrozole and rats exposed to soya isoflavones during the prenatal period, lactation, and up to sexual maturity.

The structural integrity of the germ cells in the seminiferous epithelium and the correct process of spermatogenesis are made possible by proteins that participate in the formation of different types of junctions. This study was performed on samples of the testes of 4 groups (2 experimental and 2 corresponding control) of male Wistar rats. In the first experimental group, the adult rats received letrozole - a nonsteroidal inhibitor of cytochrome P450 aromatase (P450arom). The second experimental group was exposed to soya isoflavones during the prenatal period, lactation, and up to sexual maturity. The aim of this study was to examine the immunoexpression of ß-catenin, N-cadherin, occludin, connexin43, annexin V, and advanced glycation end products (AGE) in the seminiferous epithelium of rat testes with chronic estrogen deficiency and of rats exposed to soya isoflavones. Series of sections of the testes were stained using PAS and silver impregnation. Moreover, immunohistochemistry tests were performed. A semi-quantitative determination of protein immunoexpression was performed using Image J. The number of annexin V positive Sertoli cells per tubule were counted manually. Comparisons between the experimental and corresponding control groups were performed using a non-parametric Mann-Whitney U test. The most common alterations were prematurely sloughed germ cells in the lumen of the seminiferous tubules and invaginations of the seminiferous tubules. We observed a lower number of annexin V positive Sertoli cells and a lower expression of N-cadherin and occludin in the seminiferous epithelium of both groups of rats with hormonal imbalances. Moreover, a higher expression of AGE, a lower expression of connexin 43 and a lower amount of reticular fibers in the basal lamina of seminiferous tubules was present in rats treated with letrozole and a higher expression of ß-catenin was found in rats exposed to soya isoflavones. The hormonal imbalance between androgens and estrogens resulted in a decreased number of annexin V positive Sertoli cells. This may be associated with a failed clearance of apoptotic germ cells that leads to disturbances in the blood-testis-barrier (BTB) by affecting the expression of junctional proteins in the seminiferous epithelium. Moreover, a decreased level of estrogens was also associated with an increased expression of AGEs and with a changed composition of basal lamina in the seminiferous tubules of rats. These changes could lead to germ cell sloughing and invaginations of the seminiferous tubules.

Prepubertal arsenic exposure alters phosphoproteins profile, quality, and fertility of epididymal spermatozoa in sexually mature rats.

Arsenic intoxication affects male reproductive parameters of prepubertal rats. Besides, morphological and functional alterations in their testis and epididymis may remain after withdrawal of arsenic insult, causing potential impairment in male fertility during adulthood. In this study, we aimed at analyzing the effect of prepubertal arsenic exposure on the fecundity of epididymal sperm from sexually mature Wistar rats, assessing fertility indexes, sperm parameters, and sperm phosphoproteins content. Male pups on postnatal day (PND) 21 received filtered water (controls, n = 10) and 10 mg L-1 arsenite (n = 10) daily for 30 days. From PND52 to PND81, rats from both groups received filtered water. During this period, the males mated with non-exposed females between PND72 and PND75. Our results showed that sexually mature rats presented low sperm production, epididymal sperm count, motility, and quality after prepubertal arsenic exposure. These findings possibly contributed to the low fertility potential and high preimplantation loss. Epididymal sperm proteome detected 268 proteins, which 170 were found in animals from both control and arsenic groups, 27 proteins were detected only in control animals and 71 proteins only in arsenic-exposed rats. In these animals, SPATA 18 and other five proteins were upregulated, whereas keratin type II cytoskeletal 1 was downregulated (q < 0.1). The results of KEGG pathway analysis demonstrated an enrichment of pathways related to dopaminergic response, adrenergic signaling, protein degradation, and oocyte meiosis in arsenic-exposed animals. Moreover, 26 proteins were identified by phosphoproteomic with different phosphorylation pattern in animals from both groups, but SPATA18 was phosphorylated only in arsenic-exposed animals. We concluded that prepubertal exposure to arsenic is deleterious to sperm quality and male fertility, altering the sperm phosphoproteins profile.

Effects of prenatal chlorocholine chloride exposure on pubertal development and reproduction of male offspring in rats.

Chlorocholine chloride (CCC) promote plant growth as a regulator. Emerging evidence by our group showed that CCC might restrain the puberty onset and impair the reproductive functions in male rats through HPT axis. In this study, we further investigated the effects of prenatal CCC exposure on pubertal development, reproduction of male offspring in rats and explored the underlying mechanisms. The results showed that CCC of 137.5 and 200 mg/kg bw/day delayed the age of preputial separation (PPS), decreased the sperm motility of male offspring. PP1γ2 which is an essential protein in spermatogenesis reduced in 137.5 and 200 mg/kg bw/day groups. Crucial hormones involved in hypothalamic-puititary-testicular (HPT) axis decreased at postnatal day (PND) 30. It was indicated that CCC exposure in pregnancy might disturb the pubertal development, reproductive functions of male offspring through HPT axis and disturb the sperm motility through PP1γ2.

Puberty attainment and reproductive performance of yearling Bos indicus-influenced heifers after two sequential treatments with progesterone.

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P4) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen.

Environmentally relevant perinatal exposure to DBP disturbs testicular development and puberty onset in male mice.

Di-n-butyl phthalate (DBP) is considered as a potential modifier of puberty. However, different results indicate that DBP plays an accelerated, delayed, or neutral role in the initiation of puberty. Furthermore, whether the effect of DBP on puberty will disrupt the function of reproductive system in the adults is still ambiguous. Therefore, we aimed to investigate the effect of maternal exposure to DBP on the onset of puberty in male offspring mice and the subsequent changes in the development of reproductive system. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. Compared with the control group, the 50 mg/kg/day DBP group accelerated puberty onset and testicular development were quite remarkable in male offspring mice during early puberty. Furthermore, in 22-day male offspring mice, 50 mg/kg/day DBP induced increased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in serum, and promoted the expression of steroidogenesis-related genes in the testes. Testicular Leydig cells (LCs) were isolated from the testes of 3-week-old mice and treated with 0 (control), 0.1, 1 mM monobutyl phthalate (MBP, the active metabolite of DBP) for 24 h. Consistent with the in vivo results, the expression of steroidogenesis-related genes and testosterone production were increased in LCs following exposure to 0.1 mM MBP. In adulthood, testes of the male offspring mice exposed to all doses of DBP exhibited adverse morphology compared with the control group. These results demonstrated that maternal exposure to 50 mg/kg/day DBP induced earlier puberty and precocious development of the testis, and eventually damaged the reproductive system in the later life.