Regulation of Dynamic Changes and Remodeling Events During the Formation, Rescue and Regression of the Corpus Luteum

Editorial

24 April 2020

Editorial: Regulation of Dynamic Changes and Remodeling Events During the Formation, Rescue and Regression of the Corpus Luteum

Jens Vanselow

Lane K. Christenson

and

Joy L. Pate

3,251 views

4 citations

Editors

Jens Vanselow

Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology

Lane K Christenson

University of Kansas Medical Center

Joy L Pate

The Pennsylvania State University (PSU)

Impact

Proposed pathways where Inflammation/Genetics or Environment may cause altered function of individual cells of the follicle (granulosa, oocyte and theca) to alter transcription or expression of genes by epigenetic mechanisms resulting in altered cell to cell communication, arrested follicle development, and anovulation, altered luteal function, and female infertility.

Review

29 November 2019

Perturbations in Lineage Specification of Granulosa and Theca Cells May Alter Corpus Luteum Formation and Function

Mohamed A. Abedel-Majed

, 2 more and

Andrea S. Cupp

Anovulation is a major cause of infertility, and it is the major leading reproductive disorder in mammalian females. Without ovulation, an oocyte is not released from the ovarian follicle to be fertilized and a corpus luteum is not formed. The corpus luteum formed from the luteinized somatic follicular cells following ovulation, vasculature cells, and immune cells is critical for progesterone production and maintenance of pregnancy. Follicular theca cells differentiate into small luteal cells (SLCs) that produce progesterone in response to luteinizing hormone (LH), and granulosa cells luteinize to become large luteal cells (LLCs) that have a high rate of basal production of progesterone. The formation and function of the corpus luteum rely on the appropriate proliferation and differentiation of both granulosa and theca cells. If any aspect of granulosa or theca cell luteinization is perturbed, then the resulting luteal cell populations (SLC, LLC, vascular, and immune cells) may be reduced and compromise progesterone production. Thus, many factors that affect the differentiation/lineage of the somatic cells and their gene expression profiles can alter the ability of a corpus luteum to produce the progesterone critical for pregnancy. Our laboratory has identified genes that are enriched in somatic follicular cells and luteal cells through gene expression microarray. This work was the first to compare the gene expression profiles of the four somatic cell types involved in the follicle-to-luteal transition and to support previous immunofluorescence data indicating theca cells differentiate into SLCs while granulosa cells become LLCs. Using these data and incorporating knowledge about the ways in which luteinization can go awry, we can extrapolate the impact that alterations in the theca and granulosa cell gene expression profiles and lineages could have on the formation and function of the corpus luteum. While interactions with other cell types such as vascular and immune cells are critical for appropriate corpus luteum function, we are restricting this review to focus on granulosa, theca, and luteal cells and how perturbations such as androgen excess and inflammation may affect their function and fertility.

12,754 views

52 citations

Schematic representation showing UPP and autophagy mediated proteolysis. A transcription factor, Nrf1 is liberated from the ER after stress and translocates to the nucleus, where it induces the expression of proteasome subunit genes through the ARE (antioxidant response element) by hetero-dimerizing with a small Maf (sMaf) protein. Selective autophagy is known to exert proteolysis through the recognition of unnecessary target protein via p62-LC3-autophagosome. Nrf1, NF-E2-related factor 1; sMAF, small musculoaponeurotic fibrosarcoma proteins; ARE, antioxidant response element; Ub, Ubiquitin; LC3, Microtubule-associated protein 1A/1B-light chain 3; UBA, Ubiquitin-Associated domain.

Review

19 November 2019

Possible Mechanisms for Maintenance and Regression of Corpus Luteum Through the Ubiquitin-Proteasome and Autophagy System Regulated by Transcriptional Factors

Aamir S. Teeli

, 6 more and

Hiroaki Taniguchi

4,598 views

18 citations

Original Research

15 November 2019

Proteomic Analysis of Porcine Pre-ovulatory Follicle Differentiation Into Corpus Luteum

Pawel Likszo

, 1 more and

Beenu Moza Jalali

5,218 views

12 citations

Relative mRNA level of analyzed genes in SLC (small luteal cells) and LLC (large luteal cells) obtained directly after isolation (Day 0) and after 3–5 days of culture (Experiment B). (a,b) CYP11A1, Cholesterol Side-Chain Cleavage Enzyme, (c,d) HSD3B1, 3β-hydroxysteroid dehydrogenase type 1, (e,f) PTGS2, prostaglandin-endoperoxide Synthase 2, (g,h) PGES, Prostaglandin E synthase, (i,j) PTGER2, prostaglandin E receptor 2, (k,l) PTGFR, prostaglandin F receptor, (m,n) LHCGR, luteinizing hormone/choriogonadotropin receptor, (o,p) PRLR, prolactin receptor, (q,r) FSHR, follicle stimulating hormone receptor, (s,t) GPX4, glutathione peroxidase 4, (u,v) SOD1, superoxide dismutase 1. Small letters indicate significant differences between groups, based on pairwise comparison Wilcoxon rank sum test.

Original Research

14 November 2019

Functional and Morphological Characterization of Small and Large Steroidogenic Luteal Cells From Domestic Cats Before and During Culture

Michał M. Hryciuk

, 2 more and

Katarina Jewgenow

4,239 views

13 citations

Functional networks found in upregulated differentially expressed genes (DEGs) from the contrast “day 20 treated over day 20 control.” Overrepresented functional terms of “day 20 treated” are shown. Redundant or non-informative terms were removed and the networks obtained were manually rearranged. Number of mapped genes is indicated by the node size while significance of functional terms is denoted by node color (represented in legend at the right bottom corner). Networks more highly represented in CL samples from animals treated until day 20 after ovulation were related to gene expression and translation, signaling, hormone regulation, cell differentiation and death, and immune function.

Original Research

13 November 2019

Global Transcriptomic Analysis of the Canine corpus luteum (CL) During the First Half of Diestrus and Changes Induced by in vivo Inhibition of Prostaglandin Synthase 2 (PTGS2/COX2)

Miguel Tavares Pereira

, 5 more and

Mariusz P. Kowalewski

4,129 views

7 citations

Original Research

07 November 2019

Thrombospondin 1 (THBS1) Promotes Follicular Angiogenesis, Luteinization, and Ovulation in Primates

Hannah R. Bender

, 3 more and

Diane M. Duffy

4,992 views

42 citations

Original Research

04 October 2019

Luteal Lipids Regulate Progesterone Production and May Modulate Immune Cell Function During the Estrous Cycle and Pregnancy

Camilla H. K. Hughes

, 2 more and

Joy L. Pate

6,168 views

13 citations

Original Research

10 July 2019

Prostaglandins in Superovulation Induced Bovine Follicles During the Preovulatory Period and Early Corpus Luteum

Bajram Berisha

, 3 more and

Michael W. Pfaffl

The aim of this study was to characterize the regulation pattern of prostaglandin family members namely prostaglandin F2alpha (PTGF), prostaglandin E2 (PTGE), their receptors (PTGFR, PTGER2, PTGER4), cyclooxygenase 2 (COX-2), PTGF synthase (PTGFS), and PTGE synthase (PTGES) in the bovine follicles during preovulatory period and early corpus luteum (CL). Ovaries containing preovulatory follicles or CL were collected by transvaginal ovariectomy (n = 5 cows/group), and the follicles were classified: (I) before GnRH treatment; (II) 4 h after GnRH; (III) 10 h after GnRH; (IV) 20 h after GnRH; (V) 25 h after GnRH, and (VI) 60 h after GnRH (early CL). In these samples, the concentrations of progesterone (P4), estradiol (E2), PTGF and PTGE were investigated in the follicular fluid (FF) by validated EIA. Relative mRNA abundance of genes encoding for prostaglandin receptors (PTGFR, PTGER2, PTGER4), COX-2, PTGFS and PTGES were quantified by RT-qPCR. The localization of COX-2 and PTGES were investigated by established immunohistochemistry in fixed follicular and CL tissue samples. The high E2 concentration in the FF of the follicle group before GnRH treatment (495.8 ng/ml) and during luteinizing hormone (LH) surge (4 h after GnRH, 574.36 ng/ml), is followed by a significant (P<0.05) downregulation afterwards with the lowest level during ovulation (25 h after GnRH, 53.11 ng/ml). In contrast the concentration of P4 was very low before LH surge (50.64 mg/ml) followed by a significant upregulation (P < 0.05) during ovulation (537.18 ng/ml). The mRNA expression of COX-2 increased significantely (P < 0.05) 4 h after GnRH and again 20 h after GnRH, followed by a significant decrease (P < 0.05) after ovulation (early CL). The mRNA of PTGFS in follicles before GnRH was high followed by a continuous and significant downregulation (P < 0.05) afterwards. In contrast, PTGES mRNA abundance increased significantely (P < 0.05) in follicles 20 h after GnRH treatment and remained high afterwards. The mRNA abundance of PTGFR, PTGER2, and PTGER4 in follicles before GnRH was high, followed by a continuous and significant down regulation afterwards and significant increase (P < 0.05) only after ovulation (early CL). The low concentration of PTGF (0.04 ng/ml) and PTGE (0.15 ng/ml) in FF before GnRH, increased continuously in follicle groups before ovulation and displayed a further significant and dramatic increase (P < 0.05) around ovulation (101.01 ng/ml, respectively, 484.21 ng/ml). Immunohistochemically, the granulosa cells showed an intensive signal for COX-2 and PTGES in follicles during preovulation and in granulosa-luteal cells of the early CL. In conclusion, our results indicate that the examined bovine prostaglandin family members are involved in the local mechanisms regulating final follicle maturation and ovulation during the folliculo-luteal transition and CL formation.

4,520 views

27 citations

Nodal signaling in mid CL explants cultured in vitro under hypoxia. Effect of hypoxia on (A) Nodal protein expression and (B) phosphorylation of Smad3 in mid CL explants cultured under 20% O2 or 5% O2 for 24 h (n = 4). Protein expression determined by western blot, upper panel: representative immunoblot; lower panel: densitometry of protein expression relative to β-actin expression. Values are expressed as means ± SEM in arbitrary units (AU). Statistical differences are marked with asterisks (*p < 0.05).

Original Research

01 October 2019

The Interaction Between Nodal, Hypoxia-Inducible Factor 1 Alpha, and Thrombospondin 1 Promotes Luteolysis in Equine Corpus Luteum

Edyta Walewska

, 3 more and

António Galvão

2,880 views

4 citations

Mini Review

09 July 2019

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

Konstantin Bagnjuk

and

Artur Mayerhofer

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.