Altrenogest affects the development and endocrine milieu of ovarian follicles in prepubertal and mature gilts†

2020 ◽  
Vol 103 (5) ◽  
pp. 1069-1084
Author(s):  
Adam J Ziecik ◽  
Klaudia Drzewiecka ◽  
Katarzyna Gromadzka-Hliwa ◽  
Jan Klos ◽  
Patrycja Witek ◽  
...  
Keyword(s):  
Follicular Fluid ◽  
Messenger Rna ◽  
Ovarian Follicle ◽  
Adenosine Monophosphate ◽  
Cyst Formation ◽  
Ovarian Follicles ◽  
Mrna Levels ◽  
Molecular Control ◽  
Antral Follicles ◽  
Follicular Cyst

Abstract Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared with controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, luteinizing hormone (LH)-stimulated cyclic adenosine monophosphate (cAMP) generation, and LH receptor messenger RNA (mRNA) expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2alpha metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as human chorionic gonadotropin- and forskolin-induced cAMP were also affected. In addition, altrenogest downregulated CYP17A1 mRNA in the prepubertal theca layer and PGF2alpha synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.

Steroid concentrations in fluid from human ovarian antral follicles during pregnancy

1985 ◽  
Vol 107 (1) ◽  
pp. 133-136 ◽  
Author(s):  
L. Westergaard ◽  
K. P. McNatty ◽  
I. J. Christensen
Keyword(s):  
Pregnant Women ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Ovarian Follicles ◽  
Progesterone Level ◽  
Third Trimester ◽  
Antral Follicles ◽  
Human Pregnancy ◽  
The Third ◽  
Flow Cytometric

ABSTRACT Steroid concentrations in fluid from 138 ovarian antral follicles obtained from 30 pregnant women were measured and compared with those in aspirates of 151 follicles of similar size (i.e. diameter 2–6 mm) from 61 non-pregnant women who had normal regular menstruations. The follicles were classified as healthy or atretic by flow cytometric DNA measurement of the granulosa cells contained in the follicular fluid aspirate. Nine (7%) of the follicles from pregnant women and 21 (14%) of those from non-pregnant women were healthy, and the remainder atretic (P>0·05). Androstenedione was the most abundant steroid in all follicles. Mean progesterone levels in follicular fluid from pregnant women were significantly (P<0·05) higher than in follicular fluid from non-pregnant women. In pregnant women progesterone levels were significantly (P<0·01) higher in fluid from healthy than from atretic follicles. In contrast, no significant differences in steroid concentrations were found between fluid from healthy and atretic follicles in non-pregnant women. We conclude that antral ovarian follicles may develop normally to a diameter of around 6 mm during the third trimester of human pregnancy. We also conclude that these follicles accumulate steroids in the follicular fluid in amounts which equal those found in follicles of similar size in the ovaries of non-pregnant women, but that the composition of intrafollicular steroids during pregnancy is modified towards higher concentration of progesterone. The reason for this increased intrafollicular progesterone level is unclear. J. Endocr. (1985) 107, 133–136

scholarly journals Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and -4, in bovine antral follicles

Reproduction ◽  
2005 ◽  
Vol 130 (3) ◽  
pp. 343-350 ◽  
Author(s):  
J Buratini ◽  
A B Teixeira ◽  
I B Costa ◽  
V F Glapinski ◽  
M G L Pinto ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Antral Follicles ◽  
Theca Cells ◽  
Fibroblast Growth Factor 8 ◽  
Igf I

Paracrine cell signaling is believed to be important for ovarian follicle development, and a role for some members of the fibroblast growth factor (FGF) family has been suggested. In the present study, we tested the hypothesis that FGF-8 and its cognate receptors (FGFR3c and FGFR4) are expressed in bovine antral follicles. RT-PCR was used to analyze bovineFgf8,Fgfr3candFgfr4mRNA levels in oocytes, and granulosa and theca cells.Fgf8expression was detected in oocytes and in granulosa and theca cells; this expression pattern differs from that reported in rodents. Granulosa and theca cells, but not oocytes, expressedFgfr3c, and expression in granulosa cells increased significantly with follicle estradiol content, a major indicator of follicle health.Fgfr4expression was restricted to theca cells in the follicle, and decreased significantly with increasing follicle size. To investigate the potential regulation ofFgfr3cexpression in the bovine granulosa, cells were cultured in serum-free medium with FSH or IGF-I; gene expression was upregulated by FSH but not by IGF-I. The FSH-responsive and developmentally regulated patterns ofFgfr3cmRNA expression suggest that this receptor is a potential mediator of paracrine signaling to granulosa cells during antral follicle growth in cattle.

The FSH–HIF-1α–VEGF Pathway Is Critical for Ovulation and Oocyte Health but Not Necessary for Follicular Growth in Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Chengyu Li ◽  
Zhaojun Liu ◽  
Weijian Li ◽  
Liangliang Zhang ◽  
Jilong Zhou ◽  
...  
Keyword(s):  
Ovarian Follicle ◽  
Hypoxia Inducible Factor ◽  
Oocyte Quality ◽  
Ovarian Follicles ◽  
Actin Dynamics ◽  
Independent Effect ◽  
Follicular Growth ◽  
Growth And Survival ◽  
Ovarian Follicle Development ◽  
Antral Follicles

Abstract Follicle-stimulating hormone (FSH)-induced growth of ovarian follicles is independent of follicular vascularization. Recent evidence has indicated that follicular vascularization is critical to ovarian follicle development and survival. FSH, a gonadotropin that induces follicular growth and development, also acts as the major survival factor for antral follicles. FSH has been reported to stimulate angiogenesis in the theca layers mediated in part by the vascular endothelial growth factor A (VEGFA) and the transcription factor hypoxia inducible factor 1α (HIF-1α). However, it remains largely undetermined whether FSH-dependent growth and survival of antral follicles relies on FSH-induced vascularization. Here, we first demonstrated that induction of angiogenesis through the FSH–HIF–1α-VEGFA axis is not required for FSH-stimulated follicular growth in mouse ovary. FSH increased the total number of blood vessels in mouse ovarian follicles, which was correlated with elevated expression of VEGFA and HIF-1α in granulosa cells. In contrast, blocking of follicular angiogenesis using inhibitors against the HIF-1α-VEGFA pathway repressed vasculature formation in follicles despite FSH administration. Interestingly, by measuring follicular size and ovarian weight, we found that the suppression of angiogenesis via HIF-1α–VEGFA pathway did not influence FSH-mediated follicular growth. However, inhibition of FSH-induced follicular vascularization by PX-478, a small-molecule inhibitor that suppresses HIF-1α activity, blocked ovulation and triggered atresia in large follicles. On the other hand, PX-478 injection reduced oocyte quality via impairing the meiotic apparatus, showing a prominently defective spindle assembly and actin dynamics. Collectively, our findings unveiled a vascularization-independent effect of FSH on follicular growth, whereas follicular survival, ovulation, and oocyte development relies on FSH-mediated angiogenesis in the follicles.

scholarly journals Relaxin protein and gene expression in ovarian follicles of immature pigs

1998 ◽  
Vol 21 (2) ◽  
pp. 179-187 ◽  
Author(s):  
KM Ohleth ◽  
Q Zhang ◽  
CA Bagnell
Keyword(s):  
Gene Expression ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
In Vitro Growth ◽  
Follicle Size ◽  
Theca Interna

Relaxin production by the ovarian follicle of gonadotropin-primed, prepubertal gilts is well documented. As far as we are aware, a source of relaxin in pig follicles, independent of gonadotropins, has not yet been reported. Therefore, the objective of this study was to determine whether relaxin is produced in porcine follicles in the absence of exogenous or cyclic gonadotropins. In immature pigs, immunoreactive relaxin was detected in fluids from small (1-3 mm), medium (4-5 mm) and large (>6 mm) follicles and localized to the theca interna of large follicles. Relaxin levels in follicular fluid significantly increased with follicle size (P<0.05). Relaxin mRNA was detected in whole small- and medium-sized follicles. In large follicles, the relaxin gene was expressed in thecal layers, but not granulosa cells. The abundance of relaxin transcript did not change with follicle size. In summary, relaxin protein and mRNA were detected in porcine follicles from immature animals, indicating that relaxin is produced in the porcine follicle in the absence of exogenous or cyclic gonadotropins. Relaxin's in vitro growth effects on porcine granulosa and theca cells support this follicular relaxin as a growth modulator during porcine follicular development.

scholarly journals Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Yu ◽  
Miao Liu ◽  
Zhenxin Wang ◽  
Te Liu ◽  
Suying Liu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Mrna Levels ◽  
Hormonal Changes ◽  
Male Factor ◽  
Expression Change ◽  
Ovary Syndrome ◽  
Steroid Synthesis ◽  
Pcos Group

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear. Methods Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR. Results The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels of CYP11A and HSD17B2 were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst. Conclusion Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related to HSD17B1, CYP19A1 and CYP11A1 expression change in FF exosomes.

scholarly journals Signalling pathways and mechanistic cues highlighted by transcriptomic analysis of primordial, primary, and secondary ovarian follicles in domestic cat

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shauna Kehoe ◽  
Katarina Jewgenow ◽  
Paul R. Johnston ◽  
Susan Mbedi ◽  
Beate C. Braun
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Mammalian Species ◽  
Expression Patterns ◽  
Ovarian Follicles ◽  
Domestic Cat ◽  
Transcriptional Analysis ◽  
Ovarian Folliculogenesis

AbstractIn vitro growth (IVG) of dormant primordial ovarian follicles aims to produce mature competent oocytes for assisted reproduction. Success is dependent on optimal in vitro conditions complemented with an understanding of oocyte and ovarian follicle development in vivo. Complete IVG has not been achieved in any other mammalian species besides mice. Furthermore, ovarian folliculogenesis remains sparsely understood overall. Here, gene expression patterns were characterised by RNA-sequencing in primordial (PrF), primary (PF), and secondary (SF) ovarian follicles from Felis catus (domestic cat) ovaries. Two major transitions were investigated: PrF-PF and PF-SF. Transcriptional analysis revealed a higher proportion in gene expression changes during the PrF-PF transition. Key influencing factors during this transition included the interaction between the extracellular matrix (ECM) and matrix metalloproteinase (MMPs) along with nuclear components such as, histone HIST1H1T (H1.6). Conserved signalling factors and expression patterns previously described during mammalian ovarian folliculogenesis were observed. Species-specific features during domestic cat ovarian folliculogenesis were also found. The signalling pathway terms “PI3K-Akt”, “transforming growth factor-β receptor”, “ErbB”, and “HIF-1” from the functional annotation analysis were studied. Some results highlighted mechanistic cues potentially involved in PrF development in the domestic cat. Overall, this study provides an insight into regulatory factors and pathways during preantral ovarian folliculogenesis in domestic cat.

scholarly journals Differential Effects of Gonadotropin-Releasing Hormone (GnRH) Pulse Frequency on Gonadotropin Subunit and GnRH Receptor Messenger Ribonucleic Acid Levels in Vitro*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1224-1231 ◽  
Author(s):  
Ursula B. Kaiser ◽  
Andrzej Jakubowiak ◽  
Anna Steinberger ◽  
William W. Chin
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Pulse Frequency ◽  
Gnrh Receptor ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Subunit Gene ◽  
Differential Effects ◽  
Messenger Ribonucleic Acid

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.

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