Implication of FSHB rs10835638 variant in endometriosis in Brazilian women

ABSTRACT Objective The follicle-stimulating hormone subunit beta gene rs10835638 variant (c.-211G>T) may have detrimental effects on fertility and protective effects against endometriosis. A case-control analysis was performed, aiming to investigate the possible relationship between this variant and the development and/or progression of endometriosis. Methods This study included 326 women with endometriosis and 482 controls without endometriosis, both confirmed by inspection of the pelvic cavity during surgery. Genotyping was performed using a TaqMan real-time polymerase chain reaction assay. Genotype and allele frequencies and genetic models were compared between the groups. Results The genotype and allele frequencies of the rs10835638 variant did not differ between women with and those without endometriosis. Subdividing the endometriosis group into fertile and infertile groups did not result in a significant difference in these frequencies. However, the subgroup with minimal/mild endometriosis had a higher frequency of the GT genotype than the Control Group, regardless of fertility. The T allele was significantly more common in women with minimal/mild endometriosis than in the Control Group in the recessive model. Conclusion The T allele is associated with the development of minimal/mild endometriosis in Brazilian women.

Naturally occurring genetic mutations in the 5'-upstream regulatory region of bovine FSHB generate a novel cis-regulatory element that affects its expression.

We previously reported that numerous naturally occurring genetic mutations in the 5'-upstream regulatory region (5'-URR) of the bovine follicle-stimulating hormone beta-subunit gene (FSHB) were associated with reduced serum follicle-stimulating hormone (FSH) levels, poor-quality semen and low fertility in bulls. In addition, two different FSHB mRNA transcripts resulting from the linked mutations of genomic DNA were discovered in mutation-bearing bull pituitaries. Here, using electrophoretic mobility shift assay, we identified c.-1539_-1538delGGinsTTAACT mutations in the 5'-URR that generated a novel cis-regulatory element in bovine FSHB. Moreover, this novel element seemed to play a role in repressing FSHB transcription based on a promoter activity analysis in LßT2 gonadotrope cells. Quantitative assays of FSHB mRNA in the bovine pituitaries suggested that the levels of FSHB wild-type transcripts in the mutation-bearing bulls were significantly lower (P < 0.05) than in those of bulls without FSHB genetic mutations and that the levels of FSHB-mutated transcripts were significantly lower (P < 0.05) than that of wild-type transcripts in the mutation-bearing bulls. Altogether, our results suggest that decreased serum FSH levels and male fertility in bulls with the c.-1539_-1538delGGinsTTAACT mutation likely result from the alteration of cis-regulatory elements and induction of FSHB transcription.

Comparison of follitropin ß administered by a pen device with follitropin ß administered by a conventional syringe in patients undergoing IVF-ET.

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin ß with a conventional syringe delivering follitropin ß solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin ß. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin ß is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin ß when compared with the conventional syringe.

Comparison of follitropin beta administered by a pen device with follitropin beta administered by a conventional syringe in patients undergoing IVF-ET / 대한생식의학회지

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.

Comparison of follitropin beta administered by a pen device with follitropin beta administered by a conventional syringe in patients undergoing IVF-ET / 대한생식의학회지

OBJECTIVE: To compare the effectiveness and convenience of a pen device for the self-administration of follitropin beta with a conventional syringe delivering follitropin beta solution in patients undergoing IVF-ET. METHODS: GnRH agonist long protocol was used for controlled ovarian stimulation (COS) in all subjects. A total of 100 patients were randomized into the pen device group or the conventional syringe group on the first day of COS. Local tolerance reactions were assessed within 5 minutes, at 1 hour and at 3 hours after each injection. On the day of hCG injection, patients were asked to rate their overall pain and convenience experienced with self-injection on a visual anlaogue scale (VAS). RESULTS: There were no differences in patients' characteristics between the two groups. The duration of COS was significantly shorter in the pen device group than in the conventional syringe group. Patients included in the pen device group needed a significantly smaller amount of follitropin beta. However, no differences between the two groups were found in IVF results and pregnancy outcome. The incidence of local pain within 5 minutes, at 1 hour and at 3 hours after the injection was significantly lower in the pen device group. VAS scores indicated that injections using the pen device were significantly less painful and more convenient. CONCLUSION: The pen device for self-administration of follitropin beta is less painful, safer and more convenient for the patients, and can be more effective because of the shorter duration and smaller dose of follitropin beta when compared with the conventional syringe.

Preparation and in vitro targeting of follicle stimulating hormone polypeptide modified nanoparticles / 中华妇产科杂志

Objective To prepare follicle stimulating hormone (FSH) polypeptide modified nanoparticles (NP) in order to achieve specific ovarian tumor targeting. Methods Expression of FSH receptor protein in human liver cancer and ovarian cancer cell lines BEL-7402, SKOV-3 and Caov-3 was detected by immunocytochemistry. The polypeptide fragment of FSH β 81 -95 amino acids (FSHL81-95)was synthesized and covalently coupled to NP. The specific binding of FSHL81-95 and FSHL81-95-NP was examined by fluorescence microscopy and flow cytometry. Results BEL-7402 and SKOV-3 cells were negative for FSH receptor staining, while Caov-3 celia were positive. The diameters of NP were about 100 nm, with a Zeta potential of -25 mV or so. Caov-3 cells showed a more specific interaction with FSHL81-95-NP than SKOV-3 cells (4. 17 ± 0. 86 and 2. 30 ± 0. 21 ; P < 0. 05). The uptake of FSHL81-95-NP was more than NP in Caov-3 cells (4. 17 ± 0. 86 and 0. 41 ± 0. 32 ; P < 0. 05 ). FSHL81-95-NP showed a selective targeting at Caov-3 cells compared with control NP. Conclusion FSH polypeptide modified NP could selectively target ovarian cancer cells expressing FSH receptor, which might contribute to specific endocytosis mediated by FSH receptor.