The role of endometrial lysosomes and their enzymes in endometrial bleeding

Abstract

In this study. I have investigated several aspects of endometrial morphology and function as they relate to endometrial bleeding using human endometrial biopsies. The main emphasis of this study was on endometrial lysosomes and their enzymes. Two models of endometrial bleeding were investigated. The first was a “stable” model involving postpartum breastfeeding women from days 35—210 postpartum. Under the influence of breastfeeding, endometrium was “stable” and breakthrough bleeding was rare. The second was the ''menorrhagic" model involving two groups of women. women suffering from ovulatory dysfunctional uterine bleeding (DUB) and users of copper-bearing intrauterine contraceptive devices (lUCD) in whom heavy menstrual bleeding was common.

Results showed that both lUCD treated endometrium and those from women with dysfunctional bleeding had higher numbers of lysosomes associated with higher lysosomal enzyme levels (acid phosphatase and N-acetyl-B—D-glucosaminidase) when compared with endometrium from women with entirely normal menstrual histories. An active lysosomal system appeared to contribute to menorrhagia in both users of IUCD and women with dysfunctional bleeding. However. this was not the only change present. Both groups showed other evidences of altered cellular functions. This was reflected in alterations of tissue DNA and protein content and morphological evidence of defective secretory function in lUCD-exposed endometrium (see Chapter 5. 7. 10 and 13). There must have been certain triggering mechanisms and other factors at play. Lysosomal disturbances appeared to be part of a common pathway leading to heavy menstrual bleeding.

Previous information available on postpartum endometrium was restricted to a small number of studies from two to three decades ago. In this study. I have examined postpartum endometrium in detail and demonstrated quantitative differences between postpartum and normal proliferative endometrium. The main differences were that postpartum endometrium from days 35—60 in breastfeeding women showed less tissue oedema. stromal cells were densely packed glands were few and glandular dimensions were small compared with normal. These were appearances of an inactive endometrium comparable with menstrual to early proliferative endometrium.

In the first two months postpartum. endometrial re-modelling and regeneration which took place early postpartum was still evident. This was characterised by an initial heavy leucocyte and plasma cell infiltration. abundant glandular mitochondria and endometrial lysosomes. Endometrial lysosomes participated in autophagy or heterophagy as part of normal tissue repair and regeneration. Despite abundant lysosomal activity, postpartum endometrium did not show elevated lysosomal enzyme levels and endometrial bleeding was rare.

After two months postpartum. endometrial repair was complete. Under the influence of breastfeeding, endometrial bleeding was rare and results of endometrial morphometry and ultrastructure were comparable with the mid—proliferative phase. This "stability“ would continue for long periods. a finding in accordance with past literature. The appearance of endometrial lysosomes was similar to those in the mid-proliferative phase. Lysosomal abundance present in the early postpartum period has subsided and lysosomal enzyme activity remained low.