Histopathological study of endometrial biopsy in infertility: A cross sectional study in a teaching hospital

Background: Endometrium is dynamic tissue which responds to hormones hence is the most sensitive indicator of ovarian function. Uterine pathology and cervical pathology like chronic infections or quality of cervical mucus plays a role in failure of conception. Hence endometrial biopsy is one of the most important investigations in infertility. Aim and Objectives: To document the morphological changes seen in endometrial biopsies and their demographic distribution in patients with infertility. Secondly to examine cervico-vaginal pap smear changes in infertility cases. Material and Methods: The study is a prospective cross-sectional study carried out during the period of June 2018 to July 2020. Married women visiting infertility clinic, who have undergone endometrial biopsy as an infertility evaluation were included in the study. Informed consent for the procedure was taken. Only premenstrual endometrial biopsy was included and inadequate biopsy samples were excluded from the study. Cervico-vaginal pap smear of these cases was processed under liquid-based cytology and reported using Bethesda system for cervical cytology. The histopathological findings and pap smear findings were statistically analyzed. Results: Ten percent of endometrial biopsies were indicated in evaluation of infertility among all biopsy registries. Primary infertility accounted 64% and secondary infertility as 36%. Sixty-six cases of endometrial biopsy were studied during study period. The most common histopathological findings were secretory endometrium, followed by proliferative (anovulatory and 2 cases luteal phase defect) endometrium, progestin induced changes, endometrial polyps, chronic endometritis and benign hyperplasia. Seventy-seven percentage of pap smears were negative for intraepithelial lesions (no squamous or endocervical abnormalities), predominantly showing signs of cervicitis and bacterial vaginitis. Conclusion: Histopathological study of endometrium forms an important, safe and cheaper diagnostic tool. Uterine pathology contributes to major pathogenesis of infertility and thus endometrial biopsy plays a significant role in preliminary evaluation of cases with infertility

Leishmania donovani Exploits Myeloid Cell Leukemia 1(MCL-1) Protein to Prevent Mitochondria-dependent Host Cell Apoptosis

Apoptosis is one of the mechanisms used by host cells to remove unwanted intracellular organisms, and often found to be subverted by pathogens through use of host anti-apoptotic proteins. In the present study, with the help of in vitro and in vivo approaches, we documented that the macrophage anti-apoptotic protein myeloid cell leukemia 1 (MCL-1) is exploited by the intra-macrophage parasite Leishmania donovani to protect their “home” from actinomycin D-induced mitochondria-dependent apoptosis. Among all the anti-apoptotic BCL-2 family members, infection preferentially up-regulated expression of MCL-1 at both themRNAand protein levels and compared with infected control, MCL-1-silenced infected macrophages documented enhanced caspase activity and increased apoptosis when subjected to actinomycin D treatment. Phosphorylation kinetics and ChIP assay demonstrated that infection-induced MCL-1 expression was regulated by transcription factor CREB(cAMP-response element-binding protein) and silencing of CREB resulted in reduced expression of MCL-1 and increased apoptosis. During infection, MCL-1 was found to be localized in mitochondria and this was significantly reduced in Tom70-silencedMCL-1 transport. In the mitochondria, MCL-1 interacts with the major pro-apoptotic protein BAK and prevents BAK-BAK homo-oligomer formation thereby preventing cytochrome c release-mediated mitochondrial dysfunction. Silencing of MCL-1 in the spleen of infected mice showed decreased parasite burden and increased induction of splenocyte apoptosis. Collectively our results showed that L. donovani exploited the macrophage anti-apoptotic protein MCL-1 to prevent BAK-mediated mitochondria-dependent apoptosis thereby protecting its niche, which is essential for disease progression. macrophages, suggesting the active role of TOM70 i