Distinct responses of human granulosa lutein cells after hCG or LH stimulation in a spheroidal cell culture system

Becker, Julia; Walz, Andrea; Daube, Stefanie; Keck, Christoph; Pietrowski, Detlef

doi:10.1002/mrd.20696

Cited by 11 publications

(6 citation statements)

References 26 publications

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“…A modulatory effect on cell viability and function by co-culturing different cell types was shown by Lancaster et al, for stem cell based organoid models [ 16 ]. In addition, a form of self-organization of granulosa cells and different other cells has already been described by Qiu et al [ 17 ] as well as our group [ 18 , 19 ]. De Souza and colleagues have shown that mesenchymal stem cells (MSC) increase viability and hormone production capacity of islets cells [ 20 ] and Jiang and colleagues reported a regulatory effect by endothelial cells on microglial cells [ 21 ].…”

Section: Discussionsupporting

confidence: 59%

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

Pietrowski

Grgic

Haslinger

et al. 2023

Arch Gynecol Obstet

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Purpose In humans, granulosa cells (GCs) are part of the follicle and nourish the growing oocyte. GCs produce estrogen and, after ovulation, progesterone. They are embedded in a multicellular tissue structure of the ovary, which consists of a variety of different cell types that are essential for the physiological function of the ovary. However, the extent to which individual ovarian cell types contribute to overall functionality has not yet been fully elucidated. In this study, we aim to investigate the effects of co-culturing human granulosa cells with ovarian cancer cells on their progesterone and estrogen production in an in vitro model. Methods After seeding, the cells were stimulated with 200 µM forskolin in DMEM for 72 h and the medium of the different cell culture experiments was collected. Subsequently, progesterone and oestradiol concentrations were determined using an Elisa assay. Results Morphologically, it was striking that the cells self-organize and form spatially separated areas. Compared to culturing granulosa cells alone, co-culturing human granulosa cells together with the ovarian cancer cell line OvCar-3 resulted in a significant increase in progesterone production (20.3 ng/ml versus 50.2 ng/ml; p < 0.01). Conclusions Using a simple in vitro model, we highlight the importance of cellular crosstalk between different ovarian cells in a complex cellular network and that it strongly influences granulosa cell hormone production. This could have potential implications for the procedure of transplanting endocrine tissues after cryopreservation, as it highlights the importance of survival of all cells for the functionality of the transplanted tissue.

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Section: Discussionsupporting

confidence: 59%

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

Pietrowski

Grgic

Haslinger

et al. 2023

Arch Gynecol Obstet

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“…Nonetheless, despite the usual major interest in the oocyte itself, ovarian tissue consists of many different cells which include granulosa, endothelial, and stroma cells. These are essential for ovarian function, since they are a source of hormones and since they nourish the growing oocyte, first and foremost the granulosa cells (Becker et al 2007 ; McKenzie et al 2004 ). Furthermore, angiogenesis begins within the stroma during early development of the follicles (Suzuki et al 1998 ).…”

Section: Discussionmentioning

confidence: 99%

Markers of vitality in ovaries of transmen after long-term androgen treatment: a prospective cohort study

Marschalek

Pietrowski

Dekan

et al. 2020

Mol Med

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Background Gender-affirming hormone therapy has been hypothesized to reduce the patient’s reproductive potential in transmen, although the exact long-term effects on future fertility are unknown. Methods In this prospective cohort study we aimed to evaluate ovaries of 20 transmen by using hormone serum levels, histomorphological analysis and fluorescence activated cells sorting (FACS) analysis – in order to assess the amount of vital cells. Results The median total number of follicles per field of view was 39 (IQR 12–122). Of all follicles ( n = 1661), the vast majority was primordial ( n = 1505, 90.6%), followed by primary ( n = 76, 4.6%), abnormal ( n = 63, 3.8%) and secondary follicles ( n = 17, 1.0%). FACS analysis was available for 13 samples (65.0%) and the median frequency of vital cells was 87.5% (IQR, 77.7–95.4%). Both a higher age ( p = 0.032) and a lower BMI ( p = 0.003) were significantly associated with a higher frequency of vital cells. Conclusion The majority of ovarian cells after long-term androgen treatment were vital in FACS analysis and histomorphological evaluation revealed a normal cortical follicle distribution. These results are currently exploratory, but might be promising for issues on fertility preservation. Trial registration The study was approved by the ethics committee of the Medical University of Vienna (EK 2240/2016) and was retrospectively registered in the Current Controlled Trials Register (registration number NCT03649087 , date of registration: 28.08.2018).

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“…However, initial studies on primate granulosa cells [86] did not support the concept of differential receptor activation by hCG and hLH, based on the kinetics of progesterone production. Elegant studies using human cell systems recently identified differences in the potency and chronic actions of LH and CG to stimulate cyclic AMP and progesterone secretion, plus the activation of cell signaling pathways [87, 88]. For example, LH was more potent in ERK and AKT activation to promote cell proliferation and survival, whereas hCG was more potent in cyclic AMP and steroid production.…”

Section: Extension Of Luteal Structure-function In Early Pregnancymentioning

confidence: 99%

Endocrine and local control of the primate corpus luteum

Stouffer

Bishop

Bogan

et al. 2013

Reproductive Biology

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The primate corpus luteum is a transient endocrine gland that differentiates from the ovulatory follicle midway through the ovarian (menstrual) cycle. Its formation and limited lifespan is critical for fertility, as luteal-derived progesterone is the essential steroid hormone required for embryo implantation and maintenance of intra-uterine pregnancy until the placenta develops. It is well-established that LH and the LH-like hormone, CG, are the vital luteotropic hormones during the menstrual cycle and early pregnancy, respectively. Recent advances, particularly through genome analyses and cellular studies, increased our understanding of various local factors and cellular processes associated with the development, maintenance and repression of the corpus luteum. These include paracrine or autocrine factors associated with angiogenesis (e.g., VEGF), and that mediate LH/CG actions (e.g., progesterone), or counteract luteotropic effects (i.e., local luteolysis; e.g., PGF2α). However, areas of mystery and controversy remain, particularly regarding the signals and events that initiate luteal regression in the non-fecund cycle. Novel approaches capable of gene “knockdown” or amplification”, in vivo as well as in vitro, should identify novel or underappreciated gene products that are regulated by or modulate LH/CG actions to control the functional lifespan of the primate corpus luteum. Further advances in our understanding of luteal physiology will help to improve or control fertility for purposes ranging from preservation of endangered primate species to designing novel ovary-based contraceptives and treating ovarian disorders in women. R01 HD020869, R01 HD042000, U54 HD018185, U54 HD055744, P51 OD011092, T32 HD007133, Bayer Schering Pharma AG.

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Distinct responses of human granulosa lutein cells after hCG or LH stimulation in a spheroidal cell culture system

Cited by 11 publications

References 26 publications

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production

Markers of vitality in ovaries of transmen after long-term androgen treatment: a prospective cohort study

Endocrine and local control of the primate corpus luteum

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