Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat

1996 ◽  
Vol 134 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Grietje Dijkstra ◽  
Dirk G de Rooij ◽  
Frank H de Jong ◽  
Robert van den Hurk
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Development ◽  
Follicular Development ◽  
Corpora Lutea ◽  
Hormone Levels ◽  
Antral Follicles ◽  
Ovarian Follicular Development ◽  
Serum Tsh

Dijkstra G, de Rooij DG, de Jong FH, van den Hurk R. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat. Eur J Endocrinol 1996;134:649–54. ISSN 0804–4643 The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights were measured and serum was collected to estimate thyrotrophin (TSH), folliclestimulating hormone (FSH) and inhibin levels. Two hours before sacrifice the animals received an injection of bromodeoxyuridine (BrdU) to estimate the proliferative activity of the follicular granulosa cells. Ovaries were fixed in Carnoy's fluid and follicle counts were performed on sections stained with anti-BrdU and with haematoxylin and eosin. The PTU treatment resulted in increased serum TSH levels, indicative of hypothyroidism, and markedly lower body and ovarian weights, whereas serum FSH and inhibin levels were hardly affected. At day 40, ovaries of PTU-treated animals contained relatively more secondary and less antral follicles, smaller non-atretic antral follicles and more atretic follicles when compared with untreated rats, while corpora lutea were absent. It is concluded that this disturbed folliculogenesis is due to inadequate thyroid hormone supply, which hampers the differentiation and not the proliferation of granulosa cells because diameters of antral follicles were significantly smaller whereas the BrdU-labelling index had not changed. Robert van den Hurk, Department of Functional Morphology, Faculty of Veterinary Medicine, PO Box 80.157, 3508 TD Utrecht, The Netherlands

scholarly journals The conflict between hierarchical ovarian follicular development and superovulation treatment

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Kenneth P McNatty ◽  
Derek A Heath ◽  
Norma L Hudson ◽  
Karen L Reader ◽  
Laurel Quirke ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Follicular Phase ◽  
Ovulation Rate ◽  
Cell Populations ◽  
Antral Follicles ◽  
Functional States ◽  
Ovarian Follicular Development

In mammals with a low ovulation rate phenotype, ovarian follicular development is thought to be hierarchical with few, if any, antral follicles at similar stages of development. The hypothesis being tested herein was that if most follicles are in a functionally different state, then the application of exogenous hormones to increase ovulation rate will not overcome the hierarchical nature of follicular development. Using sheep as the experimental model, the functional states of all non-atretic antral follicles ≥2 mm diameter were assessed in individual ewes (N=10/group) during anoestrus with or without pregnant mare's serum gonadotrophin (PMSG) treatment, or after a standard superovulation regimen, or during the follicular phase of the oestrous cycle. The functional states of these follicles were assessed by measuring the FSH- or human chorionic gonadotrophin (hCG)-induced cAMP responses of granulosa cellsin vitro. There were significant overall effects across the treatment groups on the responses of granulosa cells to either FSH or LH (bothP<0.001). It was concluded that for anoestrous ewes with or without PMSG treatment, and ewes during the follicular phase, granulosa cell populations of many follicles (≥2 mm diameter) did not share a similar cAMP response to FSH (∼50% of follicles) or hCG (>90% of follicles) either on a per cell or total cell basis. After superovulation, ≤30 and 10% respectively of the granulosa cell populations shared similar responses to FSH and LH with regard to follicular diameter and cAMP output. Thus, exogenous hormone treatments used routinely for increasing oocyte yield do not effectively override the hierarchical pattern of ovarian follicular development during the follicular phase.

scholarly journals 220.TGFβ1 deficient mice exhibit impaired follicle growth and luteal maintenance

2004 ◽  
Vol 16 (9) ◽  
pp. 220
Author(s):  
R. L. Robker ◽  
W. V. Ingman ◽  
S. A. Robertson
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Transforming Growth Factor ◽  
Ovarian Function ◽  
Follicular Development ◽  
Luteal Cell ◽  
Corpora Lutea ◽  
Normal Female ◽  
Female Reproduction ◽  
Antral Follicles

Transforming Growth Factor β1 (TGFβ1) is essential for normal female reproduction. Mice with a targeted deletion in the TGFβ1 gene (TGFβ1–/–) have severely impaired fertility with pregnancy occurring in <25% of mated females. TGFβ1 is implicated in several aspects of ovarian function, including potentiation of granulosa cell proliferation and suppression of luteal cell apoptosis. Our initial observations indicate that estrous cycling is disrupted in TGFβ1–/– mice and that ovulation rate is reduced. To further investigate how impaired ovarian function contributes to the infertility of TGFβ1–/– mice, ovaries were isolated from TGFβ1+/+ and TGFβ1–/– littermates at proestrus and fixed and sectioned for examination of follicle morphology and growth. BrdU labelling was performed to detect granulosa cell proliferation and blood samples were obtained for analysis of gonadotrophins and ovarian steroid hormones. Histological examination showed that ovaries from TGFβ1–/– mice were smaller than those of TGF–1+/+ mice, however large antral follicles were observed, indicating that TGFβ1 is not essential for granulosa cell proliferation. Compared to TGFβ1+/+ ovaries however, there were fewer antral follicles and only rare corpora lutea. Interestingly, in some cases there were large numbers of macrophages surrounding small follicles suggesting increased follicular atresia and/or altered macrophage activity in the TGFβ1–/– ovaries. Ovaries and serum were also isolated from females at d4 post-coital for assessment of corpora lutea morphology. TGFβ1–/– ovaries weighed less and had fewer corpora lutea than TGFβ1+/+ ovaries. TGFβ1–/– corpora lutea also contained increased numbers of apoptotic cells and infiltrating macrophages indicative of premature luteal regression. Circulating progesterone levels were reduced in TGFβ1–/– females, as was progesterone production per corpus luteum further indicating a functional defect in luteal maintenance. Cumulatively these observations show that TGFβ1 has essential roles in regulation of ovarian macrophage populations, in normal follicular development and in the generation, maintenance and steroidogenic function of corpora lutea.

Oocyte-secreted factros regulate granulosa cell steroidogenesis

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 317-321 ◽  
Author(s):  
Barbara C. Vanderhyden
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Inhibitory Factor ◽  
Preovulatory Follicles ◽  
Loss Of Contact

Investigations of strains of mice defective in germ cell development have revealed the importance of oocytes for the initial stages of folliculogenesis (Pellaset al., 1991; Huanget al., 1993). Various aspects of follicular development are dependent upon and/or influenced by the presence of oocytes, including granulosa cell proliferation (Vanderhydenet al., 1990, 1992) and cumulus expansion (Buccioneet al., 1990; Salustriet al., 1990; Vanderhydenet al., 1990; Vanderhyden, 1993). We are investigating the possibility that oocytes influence one of the primary functions of granulosa cells: steroidogenesis. In many species, granulosa cells removed from preovulatory follicles luteinisein vitro(Channinget al., 1982), presumably due to loss of contact with follicular luteinisation inhibitory factor(s). Indeed, follicular fluid can prevent granulosa cell luteinisationin vitro(Ledwitz-Rigbyet al., 1977). Follicular fluid, however, may simply be the medium for transport of factors secreted by oocytes to regulate granulosa cell activities.

scholarly journals Effects of ODC on Polyamine Metabolism, Hormone Levels, Cell proliferation and Apoptosis in Goose Ovarian Granulosa Cells

2020 ◽  
Author(s):  
Chunyang Niu ◽  
Sujuan Zhang ◽  
Guilin Mo ◽  
Yilong Jiang ◽  
Liang Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Culture Medium ◽  
Polyamine Metabolism ◽  
Hormone Levels ◽  
Apoptosis Rate ◽  
Protein Levels ◽  
Proliferation And Apoptosis

Abstract Background: Ornithine decarboxylase (ODC) plays an indispensable role in the process of polyamine biosynthesis. Polyamines are a pivotal part of living cells and have diverse roles in the regulation of cell proliferation and apoptosis, aging and reproduction. However, to date, there have been no reports about ODC regulating follicular development in goose ovaries. Here, we constructed ODC siRNA and overexpression plasmids and transfected them into goose primary granulosa cells (GCs) to elucidate the effects of ODC interference and overexpression on the polyamine metabolism, hormone levels, cell apoptosis and proliferation of granulosa cells.Results: After interfering with ODC in GCs, the mRNA and protein levels of ODC and the content of putrescine were greatly decreased (P < 0.05). When ODC was overexpressed, ODC mRNA and protein levels and putrescine content were greatly increased (P < 0.05). The polyamine-metabolizing enzyme genes OAZ1 and SSAT were significantly increased, and SPDS was significantly decreased when ODC was downregulated (P < 0.05). OAZ1, SPDS and SSAT were significantly increased when ODC was upregulated (P < 0.05). In addition, after interference with ODC, P4 (progesterone) levels in the culture medium of GCs increased greatly (P < 0.05), while the overexpression of ODC caused the P4 level to decrease significantly (P < 0.05). After ODC downregulation, granulosa cell activity was significantly reduced, the apoptosis rate was significantly increased, and the BCL-2/BAX ratio was downregulated (P < 0.05). Under ODC overexpression, the activity of GCs was notably increased, the apoptosis rate was significantly reduced, and the BCL-2/BAX protein ratio was upregulated (P < 0.05).Conclusions: Our study successfully induced ODC interference and overexpression in goose ovarian GCs, and ODC regulated mainly putrescine content in GCs with a slight influence on spermidine and spermine. Moreover, ODC participated in the adjustment of P4 levels in the culture medium of GCs, promoted granulosa cell proliferation and inhibited granulosa cell apoptosis.

scholarly journals Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization​

2021 ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
Multiple Cell ◽  
Ovarian Follicular Development

Abstract Backgrounds: Long non-coding RNA is a novel group of non-protein coding transcripts over 200nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. Results: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. Conclusions: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.

scholarly journals In ovaries with high or low variation in follicle size, granulosa cells of antral follicles exhibit distinct size-related processes

2019 ◽  
Vol 25 (10) ◽  
pp. 614-624 ◽  
Author(s):  
N G J Costermans ◽  
J Keijer ◽  
E M van Schothorst ◽  
B Kemp ◽  
S Keshtkar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Antral Follicle ◽  
Ivf Outcome ◽  
Negative Consequences ◽  
Antral Follicles ◽  
Follicle Size

Abstract Antral follicle size might be a valuable additive predictive marker for IVF outcome. To better understand consequences of antral follicle size as a marker for reproductive outcome, we aimed to obtain insight in follicle size-related granulosa cell processes, as granulosa cells play an essential role in follicular development via the production of growth factors, steroids and metabolic intermediates. Using the pig as a model, we compared gene expression in granulosa cells of smaller and larger follicles in the healthy antral follicle pool of sows, which had a high variation versus low variation in follicle size. Selected gene expression was confirmed at the protein level. Granulosa cells of smaller antral follicles showed increased cell proliferation, which was accompanied by a metabolic shift towards aerobic glycolysis (i.e. the Warburg effect), similar to other highly proliferating cells. High granulosa cell proliferation rates in smaller follicles might be regulated via increased granulosa cell expression of the androgen receptor and the epidermal growth factor receptor, which are activated in response to locally produced mitogens. While granulosa cells of smaller follicles in the pool are more proliferative, granulosa cells of larger follicles express more maturation markers such as insulin-like growth factor-1 (IGF1) and angiopoietin 1 (ANGPT1) and are therefore more differentiated. As both higher IGF1 and ANGPT1 have been associated with better IVF outcomes, the results of our study imply that including smaller follicles for oocyte aspiration might have negative consequences for IVF outcome.

scholarly journals Oocyte control of ovarian follicular development and function in mammals

Reproduction ◽  
2001 ◽  
pp. 829-838 ◽  
Author(s):  
JJ Eppig
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Dominant Factor ◽  
Ovarian Follicular Development ◽  
New Perspective ◽  
Regulatory Loop ◽  
Sphere Of Influence ◽  
And Function

A new perspective on ovarian follicular development has emerged over the last decade. Whereas the oocyte was previously considered only a passive recipient of developmental signals from oocyte-associated granulosa cells, it is now clear that communication between oocytes and granulosa cells is bidirectional. A complex interplay of regulatory factors governs the development of both types of cell. This interplay is essential not only for oocyte development but also for follicular development, beginning with the initial assembly of the primordial follicle and continuing throughout ovulation. The existence of an oocyte-granulosa cell regulatory loop, essential for normal follicular differentiation as well as for the production of an oocyte competent to undergo fertilization and embryogenesis, is proposed. Although gonadotrophins are essential for driving the differentiation of granulosa cell phenotypes, within its sphere of influence, the oocyte is probably the dominant factor determining the direction of differentiation and the function of the granulosa cells associated with it.

scholarly journals Lnc-GULP1–2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guidong Yao ◽  
Yue Kong ◽  
Guang Yang ◽  
Deqi Kong ◽  
Yijiang Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Protein Coding ◽  
Ovarian Follicle Development ◽  
Multiple Cell ◽  
Ovarian Follicular Development

Abstract Backgrounds Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1–2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1–2:1 has a regulatory effect on COL3A1. Results In this study, we found that lnc-GULP1–2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1–2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1–2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1–2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1–2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. Conclusions Lnc-GULP1–2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.

scholarly journals The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat

Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 501-513 ◽  
Author(s):  
Jennifer L Juengel ◽  
Karen L Reader ◽  
Adrian H Bibby ◽  
Stan Lun ◽  
Ian Ross ◽  
...  
Keyword(s):  
Growth Factors ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cellular Proliferation ◽  
Expression Patterns ◽  
Follicular Development ◽  
Cell Functions ◽  
Progesterone Production ◽  
Ovarian Follicular Development

The intraovarian roles of BMP family members such as BMP2, 4, 6 and 7 are not well understood, particularly in species with low ovulation rates such as sheep. Therefore, the objectives of these experiments were to determine the expression patterns of mRNAs encoding BMP2, 4, 6 and 7 during ovarian follicular development in sheep, and to determine the effects of these growth factors on ovine granulosa cell functions in vitro. For comparative purposes, the effects of these BMPs were also determined in rat granulosa cells since these factors have been most widely studied in this poly-ovulatory species. As assessed by in situ hybridization, non-atretic ovine follicles expressed mRNA for BMP6 but not 2, 4 or 7. Furthermore, expression of BMP6 was limited to the oocyte of primordial as well as primary, pre-antral and antral follicles. Reverse transcription-PCR of granulosa cell mRNA detected low levels of all the BMPs in some pools of cells. BMP2, 4, 6 and 7 each inhibited progesterone production from ovine granulosa cells without affecting cellular proliferation/survival. Similarly, these BMPs inhibited progesterone production from rat granulosa cells. However, they also stimulated cellular proliferation/survival of the rat granulosa cells highlighting a species-specific difference for these growth factors. In conclusion, in sheep, BMP2, 4, 6 and 7 inhibit granulosa cell differentiation without affecting proliferation. However, as BMP2, 4 and 7 were not detectable by in situ hybridization in any cells of non-atretic ovarian follicles, it seems unlikely that these proteins would have an important intra-ovarian role in regulating follicular development in sheep. In contrast, localization of BMP6 mRNA in the oocyte suggests that this BMP family member may have a paracrine and/or autocrine role in regulating follicular growth in sheep, as has been shown for two other oocyte derived from members of the transforming growth factor superfamily, BMP15 and growth differentiation factor 9.

scholarly journals rno-miR-128-3p promotes apoptosis in rat granulosa cells (GCs) induced by norepinephrine through Wilms tumor 1 (WT1)

2021 ◽  
Author(s):  
Ming Li ◽  
Ling Xue ◽  
Weibin Xu ◽  
Pingping Liu ◽  
Feng Li
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Wilms Tumor ◽  
Sympathetic Innervation ◽  
Follicular Development ◽  
Wilms Tumor 1 ◽  
Ovarian Follicular Development ◽  
Induced Apoptosis

AbstractThe mechanism related to ovarian follicular is complex, which has not been fully elucidated. Abundant reports have confirmed that the ovarian function development is closely related to sympathetic innervation. As one of the major neurotransmitters, norepinephrine (NE) is considered an effective regulator of ovarian functions like granulosa cell (GC) apoptosis. However, the mechanism between NE and GC apoptosis in rat is still unclear. In our study, GCs were isolated and cultured in vitro with NE treatment. The apoptosis of GCs was facilitated by NE. Wilms tumor 1 (WT1) was found to be significantly downregulated in GCs after NE treatment, and overexpression of WT1 repressed apoptosis in rat GCs induced by NE. rno-miR-128-3p was found to be significantly enhanced by NE in GCs, and inhibition of rno-miR-128-3p repressed apoptosis in rat GCs induced by NE. Mechanistically, rno-miR-128-3p interacted with WT1 and repressed its expression. In summary, inhibition of rno-miR-128-3p may enhance WT1 expression, and then repress NE-induced apoptosis in rat GCs. Our research may provide a new insight for the improvement of ovarian follicular development.

Sign in / Sign up

Export Citation Format

Share Document