GnRH analogue triptorelin acetate induces ovulation in jennies during oestrus.

Most of the northern hemisphere donkey breeds are faced with the risk of extinction, thus donkey reproduction is considered an emerging branch of theriogenology, and the management of artificial insemination and induction of ovulation is a crucial point in setting up preservation protocols. For four consecutive cycles, six jennies' ovarian activity was routinely monitored; an ultrasound examination was performed daily from the evidence of a follicle diameter ≥27 mm until ovulation. Upon reaching a follicular diameter ≥32 ± 2 mm (Hour 0), oestrous jennies were treated alternatively with 0.1 mg triptorelin acetate, sc, (TRIP), 0.4 mg/sc of buserelin acetate (BUS) or saline, sc, (CTRL) and examined ultrasonographically at Hours 14, 24, 38, 42, 48, 62 and every 24 h until ovulation. Induction of ovulation was considered successful if ovulation occurred from 24 to 48 h after treatment. 11/12 cycles resulted in ovulation for TRIP and 12/12 for BUS and CTRL groups, respectively. Mean ± SD ovulation time after treatment was 37.3 ± 8.3, 47.1 ± 21.0 and 66.8 ± 25.9 h for BUS, TRIP and CTRL, respectively (p = .0032). Ovulation rates between h24 and h48 were 10/12 (83.3%) for both TRIP/BUS and 2/12 (16.7%) for CTRL, respectively (p = .003). Buserelin and triptorelin-treated jennies had a 25 times higher probability to ovulate between Hours 24 and 48 than controls (p = .003), while there were no jenny and cycle effects on the ovulatory rate. The results of this study show how triptorelin successfully induced ovulation in jennies, like other GnRH analogues previously evaluated.

Short-term clinical and hormonal effects of a deslorelin implant on late-prepubertal bitches - Based on flare-up signs.

Gonadotropin-releasing hormone (GnRH) agonists offer an alternative to surgical sterilization in prepubertal dogs, preserving ovarian and uterine functions. However, the clinical and hormonal effects of GnRH agonist application during the late-prepubertal stage remain insufficiently understood. This study aimed to investigate the clinical effect (flare-up) and hormonal changes, specifically serum progesterone (P4) and estradiol (E2) levels, in bitches treated with 4.7 mg deslorelin acetate (DA) implants (Suprelorin®, Virbac, F) during the late prepubertal period. Sixteen clinically healthy kangal cross-breed bitches, aged 7-8 months, with a mean body weight of 20.5 ± 0.8 kg, were implanted with DA. Estrus signs were monitored daily, and blood and vaginal cytological samples were collected every other day for four weeks. Cytological changes were analyzed for overall and superficial cell index. Six out of sixteen DA-treated bitches (EST group; n = 6) exhibited clinical proestrus 8.6 ± 0.6 days after implant insertion. The mean serum concentrations of P4 and E2 at the onset of estrus were 1.38 ± 0.32 ng/ml and 37.38 ± 10.07 pg/ml, respectively. Notably, all non-estrus (N-EST group; n = 10) bitches demonstrated an increase in superficial cell index, in addition to expected cytological changes observed in the EST group. On the 18th day post-implantation, the EST group exhibited a significantly higher number of superficial cells compared to the N-EST group (p < 0.001). DA implantation resulted in cytological profile alterations accompanied by a slight increase in estrogen concentrations in all dogs. However, the flare-up response exhibited significant variability, differing from that observed in adult dogs. This study highlights the importance of meticulous timing and breed-specific considerations when utilizing DA for puberty manipulation in late-prepubertal bitches. The observed cytological and hormonal changes in response to DA implants provide valuable insights, but the variability in flare-up responses warrants further investigation.

Effects of water-soluble additive on the release profile and pharmacodynamics of triptorelin loaded in PLGA microspheres.

A satisfactory drug release profile for gonadotropin-releasing hormone (GnRH) agonist drugs is high initial release followed by small amount of drug release per day. In the present study, three water-soluble additives (NaCl, CaCl2 and glucose) were selected to improve the drug release profile of a model GnRH agonist drug-triptorelin from PLGA microspheres. The pore manufacturing efficiency of the three additives was similar. The effects of three additives on drug release were evaluated. Under the optimal initial porosity, the initial release amount of microspheres containing different additives was comparable, this ensured a good inhibitory effect on testosterone secretion in the early stage. For NaCl or CaCl2 containing microspheres, the drug remaining in the microsphere depleted rapidly after the initial release. The testosterone concentration gradually returned to an uncontrolled level. However, for glucose containing microspheres, it was found that the addition of glucose could not only increase the initial release of the drug but also assist in the subsequent controlled drug release. A good and long-time inhibitory effect on testosterone secretion was observed in this formulation. The underlying cause why the incorporation of glucose delayed the subsequent drug release was investigated. SEM results showed that considerable pores in glucose containing microspheres were healed during the microspheres incubation. After thermal analysis, an obvious glass transition temperature (Tg) depression was observed in this formulation. As Tg decreased, polymer chains are able to rearrange at lower temperatures. This, morphologic change was reflected in the gradual closure of the pores, and is the likely reason that drug release slowed down after the initial release.HIGHLIGHTSThe addition of glucose could not only increase the burst release of the drug but also delay the subsequent drug release.High initial burst and a sustained drug release helped obtain a good inhibitory effect on testosterone secretion.As Tg decreased, polymer chain was prone to rearrange. Morphologic change was reflected in the gradual closure of the pores. This was the reason that drug release slowed down after the initial burst.

EFFECTS OF A GNRH VACCINE AND DESLORELIN ACETATE IMPLANTS IN MALE FRESHWATER STINGRAYS (POTAMOTRYGON SP.).

Very little information is available in veterinary literature concerning chemical contraception in elasmobranchs. To decrease breeding and adverse reproductive behaviors, male Potamotrygon sp., housed in two zoologic institutions, were treated using methods used in other elasmobranchs. Four animals received deslorelin acetate implants (Suprelorin 4.7 mg and 9.4 mg), four animals received a gonadotropin-releasing hormone vaccine (Improvac 50-100 µg) twice separated by 1 mon, and two animals were not treated to serve as controls. Health checks, including blood sampling, coelomic ultrasound, and sperm analysis, were performed bimonthly and then monthly over almost 2 yr. Microscopic examination of sperm never revealed any significant change in concentration or motility. Size of testes and seminal vesicles glands did not change significantly after treatment. Plasma testosterone concentrations were stable (∼1 ng/ml) in intact and vaccinated animals throughout the study period. Plasma testosterone level increased significantly after deslorelin implantation and remained very high for at least 13 mon, never returning to initial values. Peak concentration varied according to the deslorelin acetate concentration used. Aggression toward females continued despite the use of contraception. Histopathologic examination on dead stingrays revealed active testicular tissue. These results suggest that deslorelin acetate implants and GnRH vaccine are ineffective at dosages used in our cases. Implants caused a continuous stimulation of the hypothalamic-pituitary-gonadal axis that could be harmful for the animals.

Vasculitis-like Palpable Purpuric Rash Induced by Decapeptyl in a Pediatric Patient Diagnosed Central Precocious Puberty

Central precocious puberty (CPP) is defined as the appearance of secondary sexual signs in girls younger than eight years of age or the onset of menarche before the age of 10 years. Gonadotropin-releasing hormone analogs (GnRHa) are the most effective therapy in CPP. Drug-induced hypersensitivity vasculitis is an inflammation of blood vessels, which may be due to the use of a number of pharmacologic agents. This case report describes drug-induced vasculitis in a girl being treated with Decapeptyl. A 7.25 year-old girl was admitted to Pediatric Endocrinology outpatients with premature breast development. She was diagnosed with CPP on the basis of physical examination and laboratory findings and tripoteline acetate (Decapeptyl®) treatment was initiated. She experienced multiple widespread skin rashes and mild abdominal pain with high temperature eight hours after the second dose of Decapeptyl. She was admitted to hospital with the diagnosis of drug-induced vasculitis and a single dose of intravenous methyl-prednisolone (1 mg/kg) and oral cetirizine was given. Her blood and urine analysis revealed no other organ involvement, other than skin. On the third day, the purpuric lesions began to resolve and had completely disappeared by the sixth day. Her treatment for CPP was switched to Depot Leuprolide acetate and she continued her treatment for two years uneventfully. To the best of our knowledge, this is the first report of a child with CPP experiencing drug-induced vasculitis due to tripotelin injection. Effective treatment may be continued by switching to an alternative gonadotropin releasing hormone analog.

Jian-Pi-Yi-Shen decoction inhibits mitochondria-dependent granulosa cell apoptosis in a rat model of POF.

As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). In vivo experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. In vitro experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 µg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. In vivo, JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. In vitro, JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.

Triptorelin-functionalized PEG-coated biosynthesized gold nanoparticles: Effects of receptor-ligand interactions on adhesion to triple negative breast cancer cells.

This paper presents the results of an experimental and computational study of the adhesion of triptorelin-conjugated PEG-coated biosynthesized gold nanoparticles (GNP-PEG-TRP) to triple-negative breast cancer (TNBC) cells. The adhesion is studied at the nanoscale using a combination of atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. The AFM measurements showed that the triptorelin-functionalized gold nanoparticles (GNP-TRP and GNP-PEG-TRP) have higher adhesion to triple-negative breast cancer cells (TNBC) than non-tumorigenic breast cells. The increased adhesion of GNP-TRP and GNP-PEG-TRP to TNBC is also attributed to the overexpression of LHRH receptors on the surfaces of both TNBC. Finally, the molecular dynamics model reveals insights into the effects of receptor density, molecular configuration, and receptor-ligand docking characteristics on the interactions of triptorelin-functionalized PEG-coated gold nanoparticles with TNBC. A three to nine-fold increase in the adhesion is predicted between triptorelin-functionalized PEG-coated gold nanoparticles and TNBC cells. The implications of the results are then discussed for the specific targeting of TNBC.

Ovulatory response to GnRH agonist during early and late fall in mares.

This study aimed to assess the ovulatory response of deslorelin acetate during the fall and the response to PGF2α 8 d post-ovulation. One hundred estrous cycles from 22 mares kept in 40° latitude were evaluated. Mares were checked by transrectal ultrasonography until a preovulatory follicle was detected and ovulation induced with deslorelin acetate. Ovulation was confirmed by ultrasonography performed at 24, 36 h post-induction and then repeated at 2-h intervals post-induction. Serum progesterone concentrations and luteal tissue area were determined daily to assess CL function. A dose of PGF2α was administered 8 d post-ovulation and interval to the subsequent ovulation was observed; each mare completed up to five cycles. The effects of local climate on endpoints were analyzed. Cycles were grouped as early (Sept 13, 2020-Oct 31, 2020; n = 55; 22 mares) and late fall (Nov 1, 2020-Dec 31, 2020; n = 45; 20 mares) based on the date of induction. The overall number of cycles with ovulations between 24 and 48 h was 90%. The number of multiple ovulations were similar between early (n = 5) and late (n = 4) fall (P = 0.87). There were no differences in deemed spontaneous ovulations occurring before 24 h between early (n = 6) and late (n = 2) fall (P = 0.29). Two failures to respond to deslorelin by 48 h were recorded in early fall and none in the late fall. The interval from induction to ovulation was similar in early (40.6 ± 0.4 h) and late (41.2 ± 0.5 h) fall (P = 0.55). The percentage of mares ovulating between 36 and 48 h post-deslorelin did not vary between early and late fall (91 vs. 95%, P = 0.21), as did not for ovulation occurring between 38 h and 44 h (62 vs. 60%, P = 0.69). Edema scores varied with time relative to ovulation (P < 0.001) and were lower in late fall (P = 0.01). Progesterone concentrations varied with time (P < 0.001) but did not differ between early and late fall (P = 0.73) and correlated weakly with the luteal area (r = 0.13; P = 0.031). Follicles <35 mm at the PGF2α had a shorter interval to the next ovulation than follicles ≥ 35 mm (9.2 ± 0.5 d vs. 10.6 ± 1.2 d) (P = 0.03). Lower temperature was associated with a smaller follicle size at induction (P = 0.0021) and ovulation (P = 0.009) and lower relative humidity was associated with a larger follicle size at ovulation (P = 0.032). In conclusion, cycling mares displayed a highly efficacious response to deslorelin acetate and apparently normal luteal function during the fall, despite lower edema scores in late fall.

Clinical use of Anti-Müllerian Hormone to monitor resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

OBJECTIVE: The use of deslorelin implants to control reproduction in cats is increasing but because of its prolonged duration, cat breeders often request implant removal before the end of the treatment. Assaying Anti Mullerian Hormone (AMH) concentrations might be useful to predict time of resumption of ovarian activity in deslorelin-treated queens following implant removal. In queens a minimum of 3 weeks during increasing photoperiod after implant removal has been described for resumption of ovarian activity but no information about AMH concentrations were observed for determining ovarian activity. ANIMALS: Sixteen queens in which deslorelin implants were surgically removed after 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively) were used in this study. PROCEDURES: A general and reproductive health check with a GnRH stimulation test were performed before the treatment. After implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection to assay AMH concentrations. RESULTS: AMH concentrations decreased significantly at the end of the treatment to ≤ 2.5 + 0.6 ng/ml (p ≤ 0.05) and reached a nadir at 1.9 ± 0.9 (p < 0.05) one-week post-removal. Following implant removal AMH concentrations started to rise reaching a value of 3.9 ± 0.7 ng/ml on the third week and were not different from pre-treatment levels on week 6 post-removal (5.8 ng/ml + 0.9, p ≥ 0.05). AMH values did not differ depending on duration of deslorelin treatment but were lower in adult queens (p < 0.05). CLINICAL RELEVANCE: AMH assay can be a useful tool to follow resumption of feline ovarian function following a deslorelin treatment.

Resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty-three queens were treated with a 4.7 mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre-treatment general and reproductive health check. Following implantation treatment, all queens in inter-oestrus-anoestrus at the time of treatment came in oestrus within 2-5 days. Starting 7-14 days following implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7 weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p < .05). In conclusion, at least 3 weeks post-removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7 mg deslorelin implant, while this time may increase up to 7 weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.

Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Long-term effect of repeated deslorelin acetate treatment in bitches for reproduction control.

Long-acting gonadotropin-releasing hormone (GnRH) analogs, which are approved for male dogs and ferrets, have been used off-label to suppress estrus in bitches predisposed to the side effects of spaying. Health data from the past 12 years were evaluated from bitches without progestogen pretreatment that received deslorelin acetate (DA) to suppress estrus for the first time before the age of 4.5 years. The study population included 32 client-owned bitches repeatedly treated with either 4.7 mg or 9.4 mg DA implants for a period of 5.3 ± 3.4 years (range 0.5-11.3 years). Follow-up information concerning immediate side effects of DA occurring within five months after the first DA treatment (n = 23) as well as long-term side effects of sustained gonadal suppression occurring after five months up to three years (n = 2), three years up to five years (n = 2) or more than five years (n = 8) were assessed through a questionnaire. Treatment was considered successful if no major side effects requiring medical treatment occurred, which applied to 26 out of 32 (81 %) bitches. In the six remaining bitches, the following major side effects led to treatment discontinuation: persistent urinary incontinence (n = 1), reoccurring induced heat (n = 1), uterine disease (n = 3) and/or ovarian tumor (n = 3). The bitches recovered completely after surgical spaying and/or DA implant removal. Minor side effects that did not require therapy or affect animal welfare included body weight changes (n = 18), subtle behavioral changes (n = 13), induced heat (n = 12), coat changes (n = 11), pseudocyesis (n = 6), transient urinary incontinence (n = 4), and/or temporary thickening of the uterine wall with little anechogenic content (n = 2). To examine a possible causal relationship between adverse side effects and DA treatment, further studies should compare the frequency of pathologies between groups of GnRH-treated, intact and spayed bitches of similar breeds and ages. Nevertheless, DA application before the age of 4.5 years may be a means of postponing surgical spaying for several years in breeds at high risk for developing urinary incontinence. Before DA is used in bitches, owners should be fully informed regarding possible side effects.

Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI.

In recent years, the conjugation of superparamagnetic iron oxide nanoparticles (SPIONs), as tumor-imaging probes for magnetic resonance imaging (MRI), with tumor targeting peptides possesses promising advantages for specific delivery of MRI agents. The objective of the current study was to design a targeted contrast agent for MRI based on Fe3O4 nanoparticles conjugated triptorelin (SPION@triptorelin), which has a great affinity to the GnRH receptors. The SPIONs-coated carboxymethyl dextran (SPION@CMD) conjugated triptorelin (SPION@CMD@triptorelin) were synthesized using coprecipitation method and characterized by DLS, TEM, XRD, FTIR, Zeta, and VSM techniques. The relaxivities of synthetized formulations were then calculated using a 1.5 Tesla clinical magnetic field. MRI, quantitative cellular uptake, and cytotoxicity level of them were estimated. The characterization results confirmed that the formation of SPION@CMD@triptorelin has been conjugated with a suitable size. Our results demonstrated the lack of cellular cytotoxicity of SPION@CMD@triptorelin, and it could increase the cellular uptake of SPIONs to MDA-MB-231 cancer cells 6.50-fold greater than to SPION@CMD at the concentration of 75 µM. The relaxivity calculations for SPION@CMD@triptorelin showed a suitable r 2 and r 2/r 1 with values of 31.75 mM-1·s-1 and 10.26, respectively. Our findings confirm that triptorelin-targeted SPIONs could provide a T 2-weighted probe contrast agent that has the great potential for the diagnosis of GnRH-positive cancer in MRI.

Gonadotropin-Releasing Hormone Agonist Versus Recombinant Human Chorionic Gonadotropin Triggering in Fertility Preservation Cycles.

The purpose of this research is to study the efficacy of GnRH-a versus r-hCG triggering in patients who go through fertility preservation cycles. This retrospective cohort study was performed in a tertiary university-affiliated medical center. It includes 191 patients undergoing fertility preservation cycles between May 2013 and September 2018, in which ovulation was induced by either GnRH-a or r-hCG. Main outcome measures were number and rate of mature oocyte. Among treatment cycles with medical indication, GnRH agonist significantly increases the odds for high mature rate by 3.55 (1.30-9.66), while in treatment cycles with social indication, there is no significant effect of the triggering agent. An advantage for GnRH-a triggering was observed in medically indicated preservation cycles.

FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty.

BACKGROUND: Clinicians have long been struggling to find an effective tool to predict onset of puberty. OBJECTIVE: To explore stimulability of inhibin B after exogenous FSH and its potential role for prediction of onset of puberty. DESIGN AND PARTICIPANTS: Study subjects were enrolled into "exploratory cohort" (n = 42) and "validation cohort" (n = 19). The exploratory cohort was further divided into group 1 (healthy children with spontaneous puberty [SP], n = 26) and group 2 (patients with hypogonadotropic hypogonadism [HH], n = 16). The validation cohort included children who presented with complaints of delayed puberty. INTERVENTION AND OUTCOME: Participants were subjected to FSH stimulation test and GnRH analogue stimulation test. Cutoffs derived from the exploratory cohort for basal and FSH stimulated inhibin B (FSH-iB) were applied on the validation cohort. Basal LH, GnRH analogue-stimulated LH, basal inhibin B, and FSH-iB were compared with clinical outcomes on a prospective follow-up for prediction of onset of puberty. RESULTS: There was statistically significant increment in inhibin B after exogenous FSH in group 1 (SP) in both male (188.8 pg/mL; P = 0.002) and female (1065 pg/mL; P = 0.023) subjects. The increment was not statistically significant in group 2 (HH) in both sexes. FSH-iB at a cutoff of 116.14 pg/mL in males and 116.50 pg/mL in females had 100% sensitivity and specificity for labelling entry into puberty. On application of these cutoffs on the validation cohort, FSH-iB had 100% positive predictive value, negative predictive value, and diagnostic accuracy for prediction of pubertal onset. CONCLUSION: Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered a novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.

The past, present and future of hormonal contraceptive use in managed captive female tiger populations with a focus on the current use of deslorelin acetate.

Tigers (Panthera tigris spp.) are endangered in the wild; ensuring sustainable insurance populations requires careful planning within zoological collections. In captive situations, contraceptives are often used to control breeding and ensure genetically viable populations that contain manageable numbers of animals; reversible contraceptives are ideal because they offer flexibility for breeding management. Historically, synthetic progestins, such as melengestrol acetate implants, were used in female tigers, but these are associated with an increased risk of reproductive pathology and subsequent infertility. Recent management advice to ex-situ collections has been to transition to the use of gonadotropin-releasing hormone agonists, such as deslorelin acetate implants, which do not appear to have a similar risk of reproductive pathology but are associated with highly variable reversal times in exotic felids. Using data from 917 contraceptive records in female tigers captured by the Association of Zoos and Aquariums Reproductive Management Center and the European Association of Zoos and Aquaria Reproductive Management Group's joint Contraception Database and from supplementary surveys, this study reviews the changing use of contraceptives in captive female tigers. The aim was to describe the historical and current use of contraceptives and provide a comprehensive assessment on the use of deslorelin implants, including data on product protocols, efficacy, pathology, and reversibility. This study determined that current dose, frequency, reversibility, and anatomical placement sites of deslorelin implants are highly variable, indicating that specific, readily available, unified, evidence-based recommendations on the use of deslorelin would be useful for future contraceptive use in managed tiger populations.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats.

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4-6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling.

An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

CONTEXT: Hormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual. OBJECTIVE: To describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones. DESIGN: Observational prospective study. SUBJECTS: 51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups. MAIN OUTCOME MEASURES: Bone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers. RESULTS: At the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment. CONCLUSIONS: BMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

Deslorelin acetate implant induces transient sterility and behavior changes in male olive baboon (Papio anubis): A case study.

This case study evaluates the effects of a 4.7 mg deslorelin acetate implant on one male olive baboon (Papio anubis). Implantation induces transient azoospermia after which the subject was able to conceive again. Behavior was also impacted with a decrease in our proxies of aggressiveness and sexual arousal.