Ovarian Reserve and Anti-Mullerian Hormone (AMH) in Mothers of Dizygotic Twins

Stroom, Elizabeth M.C. van der; König, T.E.; Vink, Jacqueline M.; Boomsma, Dorret I.; Lambalk, Cornelis B.

doi:10.1017/thg.2013.4

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…Indeed, advanced ovarian aging is a recognized feature of familial DZ twinning, with reported lower levels of anti-Mullerian hormone (AMH), a marker of lower ovarian primordial follicular reserve. 57 The rs17293443-C allele in SMAD3 also increases chances of DZ twinning, but this effect appears independent of circulating FSH levels.…”

Section: Discussionmentioning

confidence: 99%

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility

Mbarek

Steinberg

Nyholt

et al. 2016

The American Journal of Human Genetics

104

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Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.

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Section: Discussionmentioning

confidence: 99%

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility

Mbarek

Steinberg

Nyholt

et al. 2016

The American Journal of Human Genetics

104

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“…Five to ten follicles are recruited from the oocyte pool per menstrual cycle in response to the rise in FSH secretion. Selection of a dominant follicle is thought to be regulated by AMH secreted by maturing follicle granulosa cells to suppress the growth of other follicles79,80. It is possible that the age-related rise in FSH and decline in AMH may disrupt mono-ovulation and increase the incidence of two oocytes being ovulated.…”

Section: Introductionmentioning

confidence: 99%

Molecular insights into the aetiology of female reproductive ageing

et al. 2015

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As age at pubertal onset declines and age at first pregnancy increases, the mechanisms that regulate female reproductive lifespan become increasingly relevant to population health. The timing of menarche and menopause can have profound effects not only on fertility but also on the risk of diseases such as type 2 diabetes mellitus, cardiovascular disease and breast cancer. Genetic studies have identified dozens of highly penetrant rare mutations associated with reproductive disorders, and also ∼175 common genetic variants associated with the timing of puberty or menopause. These findings, alongside other functional studies, have highlighted a diverse range of mechanisms involved in reproductive ageing, implicating core biological processes such as cell cycle regulation and energy homeostasis. The aim of this article is to review the contribution of such genetic findings to our understanding of the molecular regulation of reproductive timing, as well as the biological basis of the epidemiological links between reproductive ageing and disease risk.

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“…Van Asselt and colleagues argue that the capacity of remaining follicles to produce estrogens can be relevant as well for onset of menopause28. Another explanation might be the existence of counterbalancing protective mechanisms such as recruitment in wave-like fashion of less oocytes per cycles29 or longer cycle lengths so that the total number of ovulation in a lifetime is shortened30, supported by studies that showed an earlier age at menopause for mothers of dizygotic twins compared to control mothers31,32. Germline stem cells in adult human ovaries, which could be activated postnatally under specific circumstances33 could be another possibility but robust human data is necessary to support this hypothesis34,35.…”

Section: Discussionmentioning

confidence: 99%