Human Luteinized Granulosa Cells—A Cellular Model for the Human Corpus Luteum

Abstract

In the ovary, the corpus luteum (CL) forms a temporal structure. Luteinized mural granulosa cells (GCs), which stem from the ruptured follicle, are the main cells of the CL. They can be isolated from follicular fluid of woman undergoing in vitro fertilization. In culture, human GCs are viable for several days and produce progesterone, yet eventually steroid production stops and GCs with increasing time in culture undergo changes reminiscent of the ones observed during the demise of the CL in vivo . This short review summarizes the general use of human GCs as a model for the primate CL and some of the data from our lab, which indicate that viability, functionality, survival and death of GCs can be regulated by local signal molecules (e.g., oxytocin and PEDF) and the extracellular matrix (e.g., via the proteoglycan decorin). We further summarize studies, which identified autophagocytotic events in human GCs linked to the activation of an ion channel. More recent studies identified a form of regulated cell death, namely necroptosis. This form of cell death may, in addition to apoptosis, contribute to the demise of the human CL. We believe that human GCs are a unique window into the human CL. Studies employing these cells may lead to the identification of molecular events and novel targets, which may allow to interfere with CL functions.

Compatibility of Distinct Label-Free Proteomic Workflows in Absolute Quantification of Proteins Linked to the Oocyte Quality in Human Follicular Fluid

“…In the conducted literature comparison, we focused on a few of the most comprehensive proteomic studies of human follicular fluid up to date: Zamah et al, 2015 (742 reported proteins) [ 6 ]; Bianchi et al, 2016 (617 reported proteins) [ 5 ]; Oh et al, 2017 (1079 reported proteins) [ 7 ]; Poulsen et al, 2019 (400 reported proteins) [ 4 ]; Zhang et al, 2019 (1153 reported proteins) [ 9 ]; and Pla et al, 2020 (2461 reported proteins) [ 10 ]. Furthermore, we compared the set of proteins identified in this study to the reported proteomes of biological materials in the proximate physiological environment, i.e., human plasma (Plasma Proteome Database—10,546 reported proteins) [ 21 ]; human oocyte (Virant-Klun et al, 2016—2154 reported proteins) [ 1 ]; and human granulosa cell (Bagnjuk et al, 2019—3642 reported proteins) [ 22 ]. The detailed comparison for each protein is presented in Table S8 and the general overview with cumulative data is presented in Table 2 .…”

“…[10]. Furthermore, we compared the set of proteins identified in this study to the reported proteomes of biological materials in the proximate physiological environment, i.e., human plasma (Plasma Proteome Database-10,546 reported proteins) [21]; human oocyte (Virant-Klun et al, 2016-2154 reported proteins) [1]; and human granulosa cell (Bagnjuk et al, 2019-3642 reported proteins) [22]. The detailed comparison for each protein is presented in Table S8 and the general overview with cumulative data is presented in Table 2.…”

A rapid and robust method for the cryopreservation of human granulosa cells

“…The research with primary, patient-derived human GCs holds promise for human-focused research, especially because human GCs in vitro are an apt model for the ovulatory follicle and the corpus luteum (Bagnjuk and Mayerhofer 2019). In practical terms, work with human GCs has limitations, particularly with respect to daily availability of comparable cells, given the source (i.e., individual patients) and the rapidly changing phenotype of cultured human GCs.…”

“…As GCs fulfill an essential role in the follicle, form the environment for the oocyte and produce steroids, the study of cultured human GCs provides a unique window into the human ovary. A previous study employing a proteomic comparison revealed that IVF-derived human GCs in culture resemble initially luteinizing cells of the ovulatory follicle, but then are more comparable to the large luteinized granulosa cells of the corpus luteum (CL) (Bagnjuk and Mayerhofer 2019). During the culture period, human GCs further undergo striking changes and at later time points they are alike the cells of the regressing CL (Bagnjuk and Sarah Beschta and Katja Eubler are joint first authors.…”

In focus in HCB

“…The follicular aspiration performed during assisted reproductive technology yields granulosa cells as a by-product of the procedure. These granulosa cells are key components of the follicle and, due to their characteristics and function, can provide a unique in vitro model to study the ovary (Bagnjuk and Mayerhofer 2019). However, once in culture they undergo rapid changes, and their heterogeneity arising from their human source makes them a difficult model for matching with specific patient conditions.…”