Increased Levels and Pulsatility of Follicle-Stimulating Hormone in Mothers of Hereditary Dizygotic Twins<sup>1</sup>

Lambalk, Cornelis B.; Boomsma, Dorret I.; Boer, Lonneke de; Koning, Corry H de; Schoute, E.; Popp-Snijders, Corry; Schoemaker, J.

doi:10.1210/jcem.83.2.4552

Cited by 11 publications

(3 citation statements)

References 31 publications

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“…Following this logic, it has been proposed that age-dependent twinning may also be due to natural selection favoring double ovulation events in response to declining fertility with increasing age [55]. It has also been documented that mothers of DZ twins have an increased number of FSH pulses during the early follicular phase, without a concurrent luteinizing hormone (LH) pulse [56].…”

Section: Generation Of Dz Twinsmentioning

confidence: 99%

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Biology and Genetics of Dizygotic and Monozygotic Twinning

Beck

Bruins

Mbarek

et al. 2021

Twin and Higher-Order Pregnancies

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Section: Generation Of Dz Twinsmentioning

confidence: 99%

“…A number of studies, but not all [91], have shown increased levels of plasma gonadotropins in mothers of DZ twins [56,[97][98][99].…”

Section: Endocrinology Of Dz Twinningmentioning

confidence: 99%

Biology and Genetics of Dizygotic and Monozygotic Twinning

Beck

Bruins

Mbarek

et al. 2021

Twin and Higher-Order Pregnancies

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“…A number of mothers of familial dizygotic twins show hypersecretion by the pituitary of follicle sti mul ati ng hormone (FSH). 3,4 Thi s causes mul ti pl e follicle growth, higher levels of oestrogens and multiple ovulation. 3,5,6 There i s no evi dence that the trai t of havi ng di zygoti c tw i ns i s i nheri ted i n an x-l i nked manner.…”

mentioning

confidence: 99%

Genetic risk factors in tumours of the testis: lessons from twin studies

Lambalk¹,

Boomsma

1998

Twin res.

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A thr eefol d i ncr ease for testi cul ar car ci noma has been r epor ted i n mal e di zygoti c tw i ns. I n thi s comment w e suggest the hypothesi s that over-exposur e to endogenousl y hyper secr eted Follicle Sti mul ati ng Hor mone (FSH) may underlie the pathogenesis. This is suppor ted by sever al fi ndi ngs. 1) FSH hypersecretion in mothers of dizygotic twins is most likely an autosomal trait implicating the possibility of male offspring with the same hormone characteristic. 2) In testicular carcinoma hi gher l evel s of cycl i n D2 ar e found. Thi s i s an FSH dependent sti mul ator y r egul ator of mi tosi s. 3) Ther e i s a mar k ed si mi l ar i ty betw een geogr aphi cal di str i buti on i n occur ence of di zygoti c tw i nni ng and testi cul ar car ci noma. 4) M en under goi ng sur ger y for testi cul ar car ci noma have hi gher FSH concentr ati ons and mal es w i th Dow n syndr ome have hi gher FSH l evel s and ar e mor e at r i sk to devel op testi cul ar car ci noma. We suggest to study FSH secr eti on i n mal es of familial dizygotic tw i ns and fur ther mor e the r i sk of devel opi ng testi cul ar car ci noma i n mal es w i th el evated FSH. These men w i th one testi cl e and/or w i th dysfuncti oni ng Ser tol i /Leydi g cel l s.

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

Mbarek

Steinberg

Nyholt

et al. 2016

The American Journal of Human Genetics

109

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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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Increased Levels and Pulsatility of Follicle-Stimulating Hormone in Mothers of Hereditary Dizygotic Twins¹

Cited by 11 publications

References 31 publications

Biology and Genetics of Dizygotic and Monozygotic Twinning

Biology and Genetics of Dizygotic and Monozygotic Twinning

Genetic risk factors in tumours of the testis: lessons from twin studies

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

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Increased Levels and Pulsatility of Follicle-Stimulating Hormone in Mothers of Hereditary Dizygotic Twins1

Cited by 11 publications

References 31 publications

Biology and Genetics of Dizygotic and Monozygotic Twinning

Biology and Genetics of Dizygotic and Monozygotic Twinning

Genetic risk factors in tumours of the testis: lessons from twin studies

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

Contact Info

Product

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Increased Levels and Pulsatility of Follicle-Stimulating Hormone in Mothers of Hereditary Dizygotic Twins¹