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Phospholipase C-beta1 signaling affects reproductive behavior, ovulation, and implantation.

ABSTRACT: Infertility can result from a wide range of defects, from behavioral, through germ cell development and maturation, to fertilization or embryo development. Many of the hormones regulating these processes signal via G protein-coupled receptors, which in turn activate a range of plasma membrane enzymes including phospholipase C (PLC)-beta isoforms. Transgenic mice lacking functional Plc-beta1 (Plc-beta1 KO mice) have been noted to have severely impaired fertility, but there has been little study of the reproductive processes affected by lack of this enzyme. This study examined reproductive behavior, gonadal development, fertilization, and implantation in Plc-beta1 KO mice. Male and female Plc-beta1 KO mice exhibited impaired reproductive behavior. No other defect in reproduction was noted in males, raising the possibility that the reduced fertility of Plc-beta1 KO males could be due solely to impaired behavior. In contrast, female Plc-beta1 KO mice exhibited both behavioral and nonbehavioral defects. Plc-beta1 KO females ovulated only in response to exogenous hormones, with a large proportion of in vivo embryos recovered on embryonic d 4.5 exhibiting abnormal morphology. In addition, uteri of pregnant Plc-beta1 KO females exhibited an implantation defect, with poor embryo attachment and a failure to up-regulate cyclooxygenase-2 mRNA.

SUBMITTER: Filis P

PROVIDER: S-EPMC2703520 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Phospholipase C-beta1 signaling affects reproductive behavior, ovulation, and implantation.

Filis Panayiotis P Lannagan Tamsin T Thomson Ashley A Murray Alison A AA Kind Peter C PC Spears Norah N

Endocrinology 20090402 7

Infertility can result from a wide range of defects, from behavioral, through germ cell development and maturation, to fertilization or embryo development. Many of the hormones regulating these processes signal via G protein-coupled receptors, which in turn activate a range of plasma membrane enzymes including phospholipase C (PLC)-beta isoforms. Transgenic mice lacking functional Plc-beta1 (Plc-beta1 KO mice) have been noted to have severely impaired fertility, but there has been little study o ...[more]

PMID: 19342451

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Project description:The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1? and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

Project description:Background The establishment of non-invasive diagnostic method for multiple ovulation prediction is helpful to improve the efficiency of multiple ovulation. The blood hormones and metabolites would be suitable indexes for this subject. Methods In this study, 86 estrus ewes (65 of induced estrus (IE) and 21 of spontaneous estrus (SE)) were selected and the blood samples were collected at the day before follicle-stimulating hormone (FSH) injection (1st) and before artificial insemination (2nd). The serum reproductive hormones ofFSH, luteinizing hormone (LH), 17β-Estradiol (E2), progesterone (P4) and anti-Mullerian hormone (AMH) were measured through enzyme linked immunosorbent assay (ELISA) and the untargeted metabolomics analysis was processed through LC–MS/MS. The embryos were collected after 6.5 days of artificial insemination. Results In total, 975 and 406 embryos were collected in IE and SE group, respectively. The analysis of reproductive hormones showed that concentrations of FSH, E2 and AMH were positive correlated with the embryo yield while concentrations of LH and P4 were negative correlated in both group at 1st detection. At 2nd detection, the trends of reproductive hormones were similar with 1st except P4, which was positive correlated with embryo yield. The metabolomics analysis showed that 1158 metabolites (721 in positive iron mode and 437 in negative iron mode) were detected and 617 were annotated. In 1st comparation of high and low embryonic yield populations, 56 and 53 differential metabolites were identified in IE and SE group, respectively. The phosphatidyl choline (PC) (19:0/20:5) and PC (18:2/18:3) were shared in two groups. In 2nd comparation, 48 and 49 differential metabolites were identified in IE and SE group, respectively. The PC (18:1/18:2) and pentadecanoic acid were shared. Most differential metabolites were significantly enriched in amino acid, fatty acid metabolism, digestive system secretion and ovarian steroidogenesis pathways. Conclusions This study showed that FSH, P4, AMH, the PC relevant metabolites and some anomic acids could be potential biomarkers for embryonic yield prediction in ovine multiple ovulation. The results would help to explain the relation between blood material and ovarian function and provide a theoretical basis for the multiple ovulation prediction. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-022-03387-1.

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Phospholipase C-beta1 signaling affects reproductive behavior, ovulation, and implantation.

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Phospholipase C-beta1 signaling affects reproductive behavior, ovulation, and implantation.

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