Developmental and Molecular Aberrations Associated with Deterioration of Oogenesis During Complete or Partial Follicle-Stimulating Hormone Receptor Deficiency in Mice

Yang, Yinzhi; Balla, Agneta; Danilovich, Natalia; Sairam, M.R.

doi:10.1095/biolreprod.103.015610

Cited by 33 publications

(37 citation statements)

References 42 publications

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“…These phenotypic changes were accompanied by circulating reproductive hormonal imbalance. Further molecular analysis of ovarian marker genes including those involved in oocyte and granulosa cell growth and development confirmed that the oocyte-somatic cell interactions were perturbed (Balla et al 2003, Yang et al 2003b. During this accelerated aging in heterozygous mice, prominent uterine pathology was also evident.…”

Section: Female Reproductive Phenotypes In Forko Micementioning

confidence: 80%

“…The heterozygous mice initially had reduced fertility and they stopped breeding by 7 -9 months. There was an accelerated loss of oocytes as a result of atresia and apoptosis that are typical characteristics of reproductive senescence (Balla et al 2003, Yang et al 2003b. These phenotypic changes were accompanied by circulating reproductive hormonal imbalance.…”

Section: Female Reproductive Phenotypes In Forko Micementioning

confidence: 99%

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What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

Kumar¹

2005

Reproduction

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A number of biochemical and physiological studies elucidated the roles of pituitary and placental glycoprotein hormones. Advances in the past two decades in manipulating the mouse genome by random or site-specific mutagenesis have heralded a new dimension to our understanding of the biology of gonadotropins. It is now possible to model many human reproductive disorders involving gonadotropins/gonadotropin-signaling in the mouse. Mutant mice selectively lacking either FSH or LH or their cognate receptors have been generated. The gonadotropin ligand and the corresponding receptor knockout mice mostly phenocopy each other. Analyses with these genetic models confirmed earlier physiological studies; in addition they also revealed novel roles for gonadotropins previously unrecognized. While FSH action seems dispensable for male but not female fertility, absence of LH causes infertility in both the sexes. While Sertoli cell number and germ cell carrying capacity of the Sertoli cells in compromised in FSH mutants, both somatic and germ cell lineages are affected in the LH mutants resulting in complete male infertility. FSH mutant females demonstrate a pre-antral stage block in folliculogenesis and FSH alone is not sufficient to promote full folliculogenesis in the absence of LH. Pre-ovulatory stage follicles do not form and most of the follicles undergo apoptosis in the absence of LH. Many extra-gonadal phenotypes have been described for the receptor knockout mice and whether these bear any resemblances to those in patients with similar inactivating mutations in the receptors for FSH and LH remains an open question. Thus the in vivo models will continue to have a significant impact in understanding gonadotropin physiology and pathophysiology and serve as novel genetic tools to study signaling mechanisms in the gonads.

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Section: Female Reproductive Phenotypes In Forko Micementioning

confidence: 80%

Section: Female Reproductive Phenotypes In Forko Micementioning

confidence: 99%

What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

Kumar¹

2005

Reproduction

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“…Whereas FSH stimulates GDF9 production by hamster postnatal ovaries in vitro [18], the BMP15 protein is downregulated in both Fshr-null and Fshr þ/À ovaries, indicating that FSHR and BMP15 have a direct relationship, at least at the level of translation of the latter [19]. However, a recent in vitro study in the mouse [20] has shown that, depending on the dose, FSH had either no significant effect or significantly decreased Bmp15 expression by oocyte-granulosa cell complexes from preantral follicles when compared with controls.…”

Section: Introductionmentioning

confidence: 99%

Oocyte Bone Morphogenetic Protein 15, but not Growth Differentiation Factor 9, Is Increased During Gonadotropin-Induced Follicular Development in the Immature Mouse and Is Associated with Cumulus Oophorus Expansion1

Guéripel

Brun

Gougeon

2006

Biology of Reproduction

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Bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9 are oocyte-secreted growth factors that are critical local regulators of ovarian function and may be involved in preovulatory cumulus expansion. As cumulus expansion occurs in response to the ovulatory surge, the present study was designed: 1) to investigate whether GDF9 and BMP15 are regulated by gonadotropins in the mouse ovary; and 2) to visualize changes in both GDF9 and BMP15 immunostaining in response to gonadotropins. Immature 21-day-old mice were sequentially treated with recombinant human FSH (r-hFSH), 5 IU daily, at Days 21, 22, and 23 of life, then injected with 5 IU hCG at Day 24 of life. In response to r-hFSH, steady-state Bmp15 mRNA expression levels increased in both total ovaries and cumulusoocyte complexes, whereas Gdf 9 mRNA levels did not. In addition, BMP15 protein levels increased in total ovaries. The GDF9 immunostaining was exclusively seen in growing oocytes in both control and gonadotropin-treated mice, whereas that of BMP15, which was also primarily seen in growing oocytes, exhibited important changes in response to gonadotropins. Strong BMP15 immunostaining was observed in the follicular fluid of atretic antral follicles after FSH treatment and in expanded, but not in compact, cumulus cells after hCG. The present results show for the first time that BMP15 levels increase during gonadotropininduced follicular development, in parallel with oocyte maturation, and that this local factor is likely involved in cumulus expansion as previously suggested by studies in Bmp15-null mice.cumulus cells, follicle-stimulating hormone, growth factors, oocyte development, ovary

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“…The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level. (J Histochem Cytochem 56:961-968, 2008) K E Y W O R D S octapeptide apoptotic markers immunohistochemistry flow cytometry electron microscopy intraovarian factors follicle-stimulating hormone binding inhibitor OVARIAN FOLLICULAR DEVELOPMENT is a continuous process wherein the resting follicles develop to form a mature Graffian follicle under the influence of pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (Yang et al 2003). It is well documented that, in addition to gonadotropins, intraovarian factors are also involved in the regulation of folliculogenesis (Armstrong and Webb 1997).…”

mentioning

confidence: 99%

Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

Chitnis

Navlakhe

Shinde

et al. 2008

J Histochem Cytochem.

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S U M M A R Y Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic-and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level. (J Histochem Cytochem 56:961-968, 2008)

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Developmental and Molecular Aberrations Associated with Deterioration of Oogenesis During Complete or Partial Follicle-Stimulating Hormone Receptor Deficiency in Mice

Cited by 33 publications

References 42 publications

What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

Oocyte Bone Morphogenetic Protein 15, but not Growth Differentiation Factor 9, Is Increased During Gonadotropin-Induced Follicular Development in the Immature Mouse and Is Associated with Cumulus Oophorus Expansion1

Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

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