Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability. It is a major transformational period of life, whose timing is strongly affected by genetic makeup of the individual, along with various internal and external factors. Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known, the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamo-pituitary-testicular (HPT) axis. We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context. These include (i) hypothalamic development during embryogenesis, (ii) synaptogenesis where gonadotropin releasing hormone (GnRH) neurons form neuronal connections with suprahypothalamic neurons, (iii) maintenance of neuron homeostasis, (iv) regulation of synthesis and secretion of GnRH, (v) appropriate receptors/proteins on neurons governing GnRH production and release, (vi) signaling molecules activated by the receptors, (vii) the synthesis and release of GnRH, (viii) the production and release of gonadotropins, (ix) testicular development, (x) synthesis and release of steroid hormones from testes, and (xi)the action of steroid hormones in downstream effector tissues. Defects in components of this system during embryonic development, childhood/adolescence, or adulthood may disrupt/nullify puberty, leading to long-term male infertility and/or hypogonadism. This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema. Furthermore, this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.
Adolescent ; Male ; Humans ; Adult ; Child ; Gonadotropin-Releasing Hormone ; Gonadotropins/metabolism* ; Hypogonadism ; Testis/metabolism* ; Puberty/physiology* ; Sexual Maturation

The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.
Age Factors ; Androgens/therapeutic use* ; Antispermatogenic Agents ; Cardiovascular Diseases/epidemiology* ; Contraceptive Agents, Male/therapeutic use* ; Gonadotropins/metabolism* ; Humans ; Male ; Progestins/therapeutic use* ; Testosterone/therapeutic use*

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

This study was conducted to establish an in vitro maturation (IVM) system by selection of efficient porcine serum during porcine in vitro production. To investigate the efficient porcine serum (PS), different types of PS [newborn pig serum, prepubertal gilt serum (PGS), estrus sow serum, and pregnancy sow serum] were used to supplement IVM media with or without gonadotrophin (GTH) and development rates of parthenogenetic activation (PA) and in vitro fertilization (IVF) embryos were then compared. The maturation rates of the PGS group was significantly higher when GTH was not added. Additionally, during development of PA embryos without GTH, the PGS group showed significantly higher cleavage and blastocyst formation rates. Moreover, the cleavage rates of IVF embryos were significantly higher in the PGS group, with no significant differences in the blastocyst formation. However, when GTH was supplemented into the IVM media, there were no significant differences among the four groups in the cleavage rates, development rates of the blastocyst, and cell number of the blastocyst after PA and IVF. In conclusion, PGS is an efficient macromolecule in porcine IVM, and GTH supplementation of the IVM media is beneficial when PS is used as macromolecule, regardless of its origin.
Animals ; Blastocyst/*drug effects ; Embryo, Mammalian/drug effects/*embryology/physiology/ultrastructure ; Fertilization in Vitro/veterinary ; Gonadotropins/administration & dosage/*metabolism ; In Vitro Oocyte Maturation Techniques/*methods/veterinary ; Parthenogenesis/*drug effects ; Sus scrofa/*embryology

Conservative treatment with high doses of progestin is an alternative to standard hysterectomy for young patients with early-stage endometrial adenocarcinoma who desire to preserve their fertility. Here we report a patient with well-differentiated early-stage endometrial adenocarcinoma and poor fertility potential who failed to become pregnant in two in vitro fertilization-embryo transfer cycles and suffered a relapse after conservative treatment. This case illustrates that assessment of fertility potential is critical at the time of initial evaluation and conservative treatment planning for patients with endometrial adenocarcinoma.
Adenocarcinoma ; drug therapy ; metabolism ; Adult ; Antineoplastic Agents, Hormonal ; Endometrial Neoplasms ; drug therapy ; metabolism ; Female ; Follicle Stimulating Hormone ; therapeutic use ; Gonadotropins ; therapeutic use ; Humans ; Infertility ; Pregnancy ; Progesterone ; therapeutic use ; Reproductive Techniques, Assisted

Echinomycin is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1alpha mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.
Animals ; Cells, Cultured ; Chorionic Gonadotropin/*pharmacology ; Echinomycin/*pharmacology ; Endothelin-2/genetics/*metabolism ; Female ; Gonadotropins, Equine/*pharmacology ; Granulosa Cells/drug effects/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/genetics/metabolism/physiology ; Oligonucleotides/genetics ; Ovary/cytology/drug effects/physiology ; Rats ; Rats, Sprague-Dawley ; Superovulation/*drug effects ; Transcriptional Activation

OBJECTIVETo study the effect of Bushen Tiaojing Recipe (BTR) and Xiaoyao Pill (XP) on cathepsin-L (Cat-L) mRNA in mice.

METHODSImmature mice were randomly divided into the normal group, the control group, the BTR group and the XP group, three in each group. Cat-L mRNA expression in mice was detected using reverse transcription polymerase chain reaction (RT-PCR) at 0, 4, 8 and 12 h after injecting 5 IU (human chorionic gonadotropin, HCG).

RESULTSCat-L mRNA expression increased gradually after HCG injection, the relative levels in the control group at 0, 4, 8 and 12 h were 0.066 +/- 0.005, 0.383 +/- 0.045, 0.737 +/- 0.024 and 1.036 +/- 0.073 respectively, comparisons between different time-points showed significant difference (P < 0.01). Compared with the control group, the Cat L mRNA expression was higher at 4 h in both BTR and XP groups (P < 0.01), at 8 h in the XP group (P < 0.05), and at 12 h in BTR group after injecting HCG (P < 0.05). Compared with the control group, cat L mRNA expression showed no statistic difference at 8 h in BTR group and at 12 h in XC group.

CONCLUSIONSBTR promoted the ovulation by enhancing the expression of CatL gene, and that of XP by advancing the peak of CatL gene expression.

Animals ; Cathepsin L ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gonadotropins ; administration & dosage ; Humans ; Mice ; Mice, Inbred Strains ; Ovulation ; drug effects ; RNA, Messenger ; genetics

To summarize present situation of a study on kidney-supplementing and blood-activating method in treating ovaries functional disorders (infertility with dysfunctional ovulation) for stimulating ovaries reactive mechanism to gonadotropic hormones. Refer to correlative articles and combine clinical experience to report. Kidney-supplementing and blood-activating method have obvious therapeutic effect and no side effect and no adverse reaction. More attention are paid on influence factors and contribution about kidney-supplementing and blood-activating method in treating ovaries functional disorders especially on sex hormones, ovulating, corpora luteuman and implantation factors. Indicate the necessarity to develop polycentric kidney-supplementing and blood-activating method in treating ovaries functional disorders (infertility with dysfunctional ovulation) evaluation research.
Drugs, Chinese Herbal ; therapeutic use ; Female ; Gonadotropins ; secretion ; Humans ; Infertility, Female ; drug therapy ; metabolism ; physiopathology ; Kidney ; drug effects ; physiopathology ; Ovarian Diseases ; drug therapy ; Ovary ; drug effects ; physiopathology ; Ovulation ; drug effects

OBJECTIVETo assess the effect of repeated gonadotropic stimulations on the developmental potential and growth differentiation factor-9 (GDF-9) expression of mouse oocytes.

METHODSFemale Kunming mice were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) for 3 times, and the control mice were treated with normal saline. The two groups of mice were both stimulated subsequently to obtain the mature oocytes. Immunocytochemical staining was employed to evaluate GDF-9 expression in the oocytes. The oocytes were then inseminated and cultured till the formation of blastocysts to compare the cleavage rate and blastocyst formation rate between the groups.

RESULTSA total of 253 mature oocytes were obtained in the repeated stimulation group, with a mean of 11.5 oocytes from each mouse; 521 mature oocytes were obtained in the control group with a significantly greater mean number of 32.6 from each mouse (P<0.05). The average optical density and integrated optical density for GDF-9 expression were significantly lower in the oocytes in repeated stimulation group than in the control group (P<0.05 and 0.01, respectively). After insemination, the cleavage rate were comparable between repeated stimulation group and the control group (85.6% vs 88.8%), but the blastocyst formation rate was significantly lower in repeated stimulation group (20.8% vs 35.2%, P<0.01).

CONCLUSIONRepeated gonadal stimulation decreases the developmental potential of mouse oocytes possibly due to reduced GDF-9 expression.

Animals ; Cells, Cultured ; Female ; Gonadotropins ; pharmacology ; Growth Differentiation Factor 9 ; metabolism ; Mice ; Oocytes ; cytology ; growth & development ; metabolism ; Ovulation Induction ; adverse effects ; methods

OBJECTIVETo evaluate the influence of superovulation by GnRHa protocol and pregnant mare's serum gonadotropin (PMSG) alone on the expression of estrogen receptor (ER), progesterone receptor (PR) and leukemia inhibitory factor (LIF) mRNA on endometrium.

METHODSForty-five female ICR mice were randomly allocated into 3 groups:(1) GnRHa+PMSG group: alarelin was give first for desensitizing the pituitary, then superovulation with PMSG; (2) PMSG group: mice were injected with PMSG only; (3) Natural cycle group: mice were given with same volume of saline. Endometrium samples were taken at 48 hours after given hCG or ovulation (control group). ER and PR in glandular cells were detected with SP immunohistochemistry semiquantitatively. Expression of LIF mRNA on endometrium was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

RESULTThe positive rate(%) and expression intense (AU) of ER and PR on glandular epithelium cells were significantly lower in GnRHa+PMSG group and PMSG group than those in natural cycle group (all P <0.01). The expression of LIF mRNA was significantly lower in GnRHa+PMSG group and PMSG group than that in natural cycle group (all P <0.01); but the expressions of ER, PR and LIF in GnRHa+PMSG group were higher than those in PMSG group.

CONCLUSIONThe protocol with GnRHa down regulates the expressions of ER, PR and the LIF mRNA on the mice of secretive phase endometrium, suggesting it may have an adverse effect on the endometrial receptivity in mice, but it may still be better than PMSG alone.

Animals ; Clinical Protocols ; Endometrium ; metabolism ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; pharmacology ; Gonadotropins ; pharmacology ; Leukemia Inhibitory Factor ; metabolism ; Mice ; Mice, Inbred ICR ; Ovulation Induction ; methods ; RNA, Messenger ; metabolism ; Random Allocation ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Superovulation ; metabolism