Primary ovarian insufficiency

Vos, Michel De; Devroey, Paul; Fauser, Bart C.J.M.

doi:10.1016/s0140-6736(10)60355-8

Cited by 590 publications

(308 citation statements)

References 135 publications

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“…Regardless of these classifications, our observations suggest that bovine ovaries with low mid-AFC are comparable to POF ovaries, indicating early ovarian senescence. This idea is supported by the fact that, in our model (population of cows with Lo ovaries), the quantity of mid-antral follicles on the ovarian surface exhibited a significant positive correlation with the total number of primordial follicles, as described previously in dairy cows (Cushman et al 1999) and in women during the perimenopausal period (Hansen et al 2008;Broekmans et al 2009) or affected by POF (De Vos et al 2010;Monget et al 2012). This observation is important because exhaustion of the pool of primordial follicles within the ovarian cortex is the cause of primary ovarian insufficiency in most young women (De Vos et al 2010).…”

Section: Discussionsupporting

confidence: 87%

“…Two major reasons for the development of POF have been proposed: (1) failure to acquire an adequate number of initial primordial follicles, which normally takes place during fetal life; and (2) excessive clearance of primordial follicles, together with the suppressed activation and further development of primordial follicles (Jagarlamudi et al 2010). The aetiology of most of cases of POF is idiopathic; however, this condition has a heterogenous background (Nelson 2009;De Vos et al 2010) and, in the past decade, an increasing number of genes has been implicated in premature ovarian failure (Goswami and Conway 2005;Skillern and Rajkovic 2008;van Dooren et al 2009;Persani et al 2010;Cordts et al 2011). Light and transmission electron microscopy studies have led to the identification of two POF phenotypes: follicular and afollicular POF ovaries (Haidar et al 1994;Massin et al 2004Massin et al , 2008.…”

Section: Discussionmentioning

confidence: 99%

“…Diminished ovarian reserve, associated with a drop in ovarian volume and vascularity, generally predicts a poor response to gonadotropin, limits the possibility of successful pregnancy and is correlated with the occurrence of menopausal transition (Lass and Brinsden 1999;Kwee et al 2007;La Marca et al 2012). A low AFC has been described in women during the perimenopausal period (Hansen et al 2008;Broekmans et al 2009), as well as in young infertile and subfertile women affected by premature ovarian failure (POF;De Vos et al 2010;Monget et al 2012), suggesting that the factors affecting the size of the follicular reserve also affect the quality of the remaining oocytes and the likelihood of conception (Rosen et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

Modina

Tessaro

Lodde

et al. 2014

Reprod. Fertil. Dev.

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Abstract. High-producing dairy cows are subfertile; however, the mechanisms responsible for the decreased fertility are unknown. The aim of the present study was to test the hypothesis that culled dairy cows (4-8 years old) characterised by 'Lo' ovaries (i.e. those with ,10 mid-antral follicles) are affected by premature ovarian senescence. Cows in which both ovaries were 'Lo' ovaries represented 5% of the total population analysed, and exhibited reduced ovarian size (P , 0.001) and increased perifollicular stroma (P , 0.05) compared with age-matched controls (i.e. cows in which both ovaries had .10 mid-antral follicles; 'Hi' ovaries). The total number of follicles, including healthy and atretic primordial, primary, secondary and small antral follicles, was lower in Lo ovaries (P , 0.01). Interestingly, the primordial follicle population in Lo ovaries was lower (P , 0.05) than in the control. Finally, the follicular fluid of mid-antral follicles from Lo ovaries had reduced oestradiol and anti-Müllerian hormone levels (P , 0.05), but increased progesterone concentrations (P , 0.05). Together, these data account for the reduced fertility of cows with Lo ovaries and are in agreement with previous observations that oocytes isolated from Lo ovaries have reduced embryonic developmental competence. Cows with a specific Lo ovary condition may represent a suitable model to address the causes of low fertility in high-yielding dairy cows, as well as the condition of premature ovarian aging in single-ovulating species.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

Modina

Tessaro

Lodde

et al. 2014

Reprod. Fertil. Dev.

View full text Add to dashboard Cite

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“…POF is defined as amenorrhea for at least 4 months before the age of 40 years, combined with a decreased serum concentration of estradiol and an increased serum concentration of follicle-stimulating hormone (FSH >40 IU/l) [10]. Only little is known about the molecular mechanisms of FOXL2 dysregulation in the ovary of a BPES patient.…”

Section: Foxl2 Impairment In Bpesmentioning

confidence: 99%

<i>FOXL2 </i>Impairment in Human Disease

Verdin¹,

Baere²

2012

Horm Res Paediatr

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FOXL2 encodes a forkhead transcription factor that plays important roles in the ovary during development and in post-natal, adult life. Here, we focus on the clinical consequences of FOXL2 impairment in human disease. In line with other forkhead transcription factors, its constitutional genetic defects and a somatic mutation lead to developmental disease and cancer, respectively. More than 100 unique constitutional mutations and regulatory defects have been found in blepharophimosis syndrome (BPES), a complex eyelid malformation associated (type I) or not (type II) with premature ovarian failure (POF). In agreement with the BPES phenotype, FOXL2 is expressed in the developing eyelids and in fetal and adult ovaries. Two knock-out mice and at least one natural animal model, the Polled Intersex Syndrome goat, are known. They recapitulate the BPES phenotype and have provided many insights into the ovarian pathology. Only a few constitutional mutations have been described in nonsyndromic POF. Moreover, a recurrent somatic mutation p.C134W was found to be specific for adult ovarian granulo-sa cell tumors. Functional studies investigating the consequences of FOXL2 mutations or regulatory defects have shed light on the molecular pathogenesis of the aforementioned conditions, and contributed considerably to genotype-phenotype correlations. Recently, a conditional knock-out of Foxl2 in the mouse induced somatic transdifferentiation of ovary into testis in adult mice, suggesting that Foxl2 has an anti-testis function in the adult ovary. This changed our view on the ovary and testis as terminally differentiated organs in adult mammals. Finally, this might have potential implications for the understanding and treatment of frequent conditions such as POF and polycystic ovary syndrome.

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“…Two main factors contribute to these disorders, the age of the woman and reproductive capacity. The current study aimed to understand how hypothalamic-pituitary-gonadal (HPG) axis regulates the pituitary hormone (luteinizing hormone, LH) and ovarian follicle development during prepubertal, pubertal and adulthood in male and female mice.The onset of puberty and sexual function are mainly triggered by the activation of HPG axis, which produces pulsatile gonadotropin (LH and FSH) release during secondary sexual development, and regulates gonadal steroid hormone (estradiol and testosterone) synthesis [4][5][6][7][8][9][10][11][12][13][14][15]. Hormonal indicators can be used as tools for detecting early pubertal onset in mammals, but there are limited studies on the hormonal profile changes that occur during the pubertal transitions from prepuberty to early-adulthood in males and females [16,17].…”

mentioning

confidence: 99%

The refinement of the pulsatile Luteinizing Hormone (LH) profile following pubertal maturation: a potential mechanism for enhanced recruitment of ovarian follicles for improved fertility

Wan¹

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Ten to fifteen percent of couples experience infertility [1], which for many can be a life crisis [2,3]. Defects in ovulation and spermatogenesis, as well as unexplained causes, account for the major component of impaired fertile aetiologies [1]. Two main factors contribute to these disorders, the age of the woman and reproductive capacity. The current study aimed to understand how hypothalamic-pituitary-gonadal (HPG) axis regulates the pituitary hormone (luteinizing hormone, LH) and ovarian follicle development during prepubertal, pubertal and adulthood in male and female mice.The onset of puberty and sexual function are mainly triggered by the activation of HPG axis, which produces pulsatile gonadotropin (LH and FSH) release during secondary sexual development, and regulates gonadal steroid hormone (estradiol and testosterone) synthesis [4][5][6][7][8][9][10][11][12][13][14][15]. Hormonal indicators can be used as tools for detecting early pubertal onset in mammals, but there are limited studies on the hormonal profile changes that occur during the pubertal transitions from prepuberty to early-adulthood in males and females [16,17]. The mouse, a powerful model often used to elucidate the genetic basis of human physiology and pathophysiology [18], remains highly challenging to study functionally in the context of hormonal release. This is particularly true for LH release, owing to an inability to accurately detect pulsatile LH release in the ultra-small blood fractions available in mice. Quantitative measures of pulsatile LH in pre-pubertal and post-pubertal female and male mice therefore do not exist. As patterns of LH release are more pulsatile compared to FSH, we aimed to examine the pulsatile LH secretion during the transition of puberty in both male and female mice in this project. Dynamic changes in LH release that occur with age and reproductive cycle will provide vital information that predicts optimal reproductive capacity.The current project described the generation of an ultra sensitive mouse LH enzymelinked immunosorbent assay (ELISA) capable of reliably detecting LH to 0.117 ng/mL in a 2-µL fraction of mouse whole blood. Male C57BL/6J mice were used to quantify the pulsatile LH secretion profile during the transition from prepuberty to adulthood. This method has been validated using terminal male mouse plasma and whole blood 3 samples collected using an established frequent blood procedure [19]. Data demonstrated the peak of episodic LH release rarely exceeded 3 ng/mL in both 4 weeks and 16 weeks of age in wild-type C57BL/6J male mice [20]. Mice with an absence or disruption to the kisspeptin receptor (Gpr54/Kiss1r) [21][22][23][24][25] and Kisspeptin 1 (Kiss1) [26] genes do not undergo normal pubertal development and result in impaired fertility in both sexes. Mutations in GPR54 in humans results in absent LH secretion [25, 27,28]. We validated this LH assay by undertaking highresolution serial blood sampling to determine levels of pulsatile LH secretion in 32-week-old male kisspeptin rece...

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Primary ovarian insufficiency

Cited by 590 publications

References 135 publications

Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

Reductions in the number of mid-sized antral follicles are associated with markers of premature ovarian senescence in dairy cows

<i>FOXL2 </i>Impairment in Human Disease

The refinement of the pulsatile Luteinizing Hormone (LH) profile following pubertal maturation: a potential mechanism for enhanced recruitment of ovarian follicles for improved fertility

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