Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003128 (anovulation)
 1,718 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aims of these studies were to determine the abilities of antisera against different regions of ovine bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) to inhibit ovarian follicular activity, estrus (mating), and ovulation in sheep. The 9-15-mer peptides were conjugated to keyhole limpet hemocyanin (KLH) and used to generate antibodies against the flexible N-terminal regions of the mature protein as well as against regions in which dimerization of the protein or interaction with a type 1 BMP or a type 2 TGFB or BMP receptor was predicted to occur. Ewes (n = 10 per treatment group) were vaccinated with KLH or the KLH-BMP15 (n = 9 different peptides) or KLH-GDF9 (n = 10) peptides in Freund adjuvant at five consecutive monthly intervals. Overall, antisera generated against peptides that corresponded to amino acid residues 1-15 of the N-terminus of the BMP15 or GDF9 mature protein or GDF9 amino acid residues 21-34 were the most potent at inhibiting ovulation following primary and single booster vaccination. Several other BMP15 (8/9) or GDF9 (6/10) treatment groups, but not KLH alone, also produced significant reductions in the numbers of animals that ovulated, although 2, 3 or 4 booster vaccinations were required. Anovulation was commonly associated with the inhibition of normal ovarian follicular development and anestrus. The in vitro neutralization studies with IgG from the BMP15 or GDF9 immunized ewes showed that the mean inhibition of BMP15 plus GDF9 stimulation of (3)H-thymidine uptake by rat granulosa cells was approximately 70% for animals without corpora lutea (CL), whereas for animals with one to three CL or more than three CL, the inhibition was 24%-33% or 27%-42%, respectively. In summary, these data suggest that reagents that block the biological actions of BMP15 or GDF9 at their N-termini have potential as contraceptives or sterilizing agents.
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PMID:The effects of immunizing sheep with different BMP15 or GDF9 peptide sequences on ovarian follicular activity and ovulation rate. 1709 1

Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2 diabetes mellitus), are associated with menstrual dysfunction, anovulation, infertility, and early pregnancy loss. Ovarian dysfunction is not only related to low pregnancy rates but also to the increased risk of miscarriage. Women with PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian dysfunction. In this study, we first explored whether high insulin levels directly affected ovarian functioning during embryo implantation. Mice in the insulin-treated group were given a subcutaneous injection of human recombinant insulin. After insulin treatment, serum levels of E2 (estrogen), PROG (progesterone), LH (luteinizing hormone), and FSH (follicle-stimulating hormone) were obviously lower, and there was a significant decrement of ovarian GDF9 (growth differentiation factor 9) mRNA. H&E (hematoxylin and eosin) staining showed a greater number of immature follicles and less luteinization in the insulin group. Further autophagy was studied in this process. A significant increase of P62 (SQSTM1/Sequestosome1) and a decrease of Cathepsin B, BECN1 (Beclin 1), and ULK1 (Unc-51-like kinase 1) mRNA in ovary was found in the insulin group. Western blot analysis showed that the expressions of LC3 (microtubule-associated protein 1 light chain 3), BECN1, and Cathepsin B proteins in ovaries from insulin group were obviously reduced, while P62 proteins were significantly increased. All these results illustrated that insulin could directly impair ovarian function during embryo implantation and the imbalance of ovarian autophagy due to insulin. Autophagy could enhance the impaired ovarian function results from insulin.
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PMID:High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process. 2842 Aug 20