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• W4237788904 abstract "Ilona Rjasanowski and colleagues1Rjasanowski I Klöting I Kavacs P Altered sex ratio in offspring of mothers with insulin-dependent diabetes mellitus.Lancet. 1998; 351: 497-498Summary Full Text Full Text PDF PubMed Scopus (37) Google Scholar describe a disturbance in the sex ratio at birth with a 50% loss of male offspring in women with insulin-dependent diabetes mellitus (IDDM). In 1974, we reported that diet deficient in an essential fatty acid (EFA) fed to female mice before and throughout reproduction changed the sex ratio from 101·5 males/100 females to 32·2 males/100 females, a loss of over 60% of males.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google ScholarWe have also investigated the essential-fatty-acid status of pregnant diabetic women and their babies by taking blood samples from the mother and cord at birth and measuring the fatty acids as a proportion of the total fatty acids in individual lipid fractions. We found a reduction in the EFA docosahexaenoic acid (DHA) in pregnant women in the choline phosphoglycerides of erythrocyte membranes in 14 women with IDDM (5·8% [SD 0·7] vs 8·7% [0·9] in 74 controls, p<0·01) and with arachidonic acid in 34 women with gestational diabetes (13·8% [1·2] vs 16·8% [1·9 in the controls], p<0·05).The Δ-6 desaturase limits the rate of conversion of linoleic to arachidonic and α-linolenic to DHA.3Sprecher H Interconversions between 20-and 23-carbon n-3 and n-6 fatty acids via 4-desaturase independant pathways.in: Sinclair AJ Gibson R IIIrd International Congress on essential fatty acids and eicosanoids. American Oil Chemical Society, Adelaide, Champaign, USA1993: 18-22Google Scholar The Δ-6 desaturase activity is further reduced in diabetes.4Brenner RR Nutritional and hormonal factors influencing desaturation of essential fatty acids.Prog Lipid Res. 1981; 20: 41-47Crossref PubMed Scopus (487) Google Scholar There are two rate limiting Δ-6 desaturations in the synthesis of DHA which would be especially affected in diabetes, consistent with our data.Arachidonic acid and DHA are selectively transferred from the mother to the fetus. Hence, during pregnancy, DHA supplies in the mother are under stress in the last trimester and a relative deficiency is thought to occur. This situation is exacerbated in diabetic pregnancies as our data show. Vascular dysfunction has also been described in gestational diabetes.5Knock GA McCarthy AL Lowy C Poston L Association of gestational diabetes with abnormal maternal vascular endothelial function.By J Obstet Gynaecol. 1997; 104: 229-234Crossref PubMed Scopus (74) Google Scholar We have recently reproduced both the DHA deficit and vascular dysfunction in pregnant rats that affected their offspring.We conclude that diabetes induces a selective EFA deficiency in pregnancy. Male animals are known to be more susceptible to EFA deficiency, so the reduction in male offspring born to EFA-deficient mothers was explained as a higher prenatal male mortality.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google Scholar The intrauterine sex bias is seen in anthropometry at birth so gender sensitivity to EFA is not only apparent before sexual maturity but before birth. That it was intrauterine loss of males was established by the reduction in litter size without any change in the number of females born.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google Scholar The similarity of our finding with that reported by Rajasanowski and co-workers of a loss of male offspring in diabetic pregnant women in whom a DHA deficit would be expected, is striking.The change in sex ratio in mice with EFA deficiency, experimental and then human evidence of a metabolic EFA deficiency in diabetes, evidence of diabetic vascular dysfunction followed by the change in sex ratio in the offspring of women with IDDM completes a circle of evidence that intrauterine lipid milieu affects the products of conception.This work is supported by the British Diabetic Association, the March of Dimes, Christopher H R Reeves Charitable Trust, and the Mother and Child Foundation. We thank B Thomas for her contribution. Ilona Rjasanowski and colleagues1Rjasanowski I Klöting I Kavacs P Altered sex ratio in offspring of mothers with insulin-dependent diabetes mellitus.Lancet. 1998; 351: 497-498Summary Full Text Full Text PDF PubMed Scopus (37) Google Scholar describe a disturbance in the sex ratio at birth with a 50% loss of male offspring in women with insulin-dependent diabetes mellitus (IDDM). In 1974, we reported that diet deficient in an essential fatty acid (EFA) fed to female mice before and throughout reproduction changed the sex ratio from 101·5 males/100 females to 32·2 males/100 females, a loss of over 60% of males.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google Scholar We have also investigated the essential-fatty-acid status of pregnant diabetic women and their babies by taking blood samples from the mother and cord at birth and measuring the fatty acids as a proportion of the total fatty acids in individual lipid fractions. We found a reduction in the EFA docosahexaenoic acid (DHA) in pregnant women in the choline phosphoglycerides of erythrocyte membranes in 14 women with IDDM (5·8% [SD 0·7] vs 8·7% [0·9] in 74 controls, p<0·01) and with arachidonic acid in 34 women with gestational diabetes (13·8% [1·2] vs 16·8% [1·9 in the controls], p<0·05). The Δ-6 desaturase limits the rate of conversion of linoleic to arachidonic and α-linolenic to DHA.3Sprecher H Interconversions between 20-and 23-carbon n-3 and n-6 fatty acids via 4-desaturase independant pathways.in: Sinclair AJ Gibson R IIIrd International Congress on essential fatty acids and eicosanoids. American Oil Chemical Society, Adelaide, Champaign, USA1993: 18-22Google Scholar The Δ-6 desaturase activity is further reduced in diabetes.4Brenner RR Nutritional and hormonal factors influencing desaturation of essential fatty acids.Prog Lipid Res. 1981; 20: 41-47Crossref PubMed Scopus (487) Google Scholar There are two rate limiting Δ-6 desaturations in the synthesis of DHA which would be especially affected in diabetes, consistent with our data. Arachidonic acid and DHA are selectively transferred from the mother to the fetus. Hence, during pregnancy, DHA supplies in the mother are under stress in the last trimester and a relative deficiency is thought to occur. This situation is exacerbated in diabetic pregnancies as our data show. Vascular dysfunction has also been described in gestational diabetes.5Knock GA McCarthy AL Lowy C Poston L Association of gestational diabetes with abnormal maternal vascular endothelial function.By J Obstet Gynaecol. 1997; 104: 229-234Crossref PubMed Scopus (74) Google Scholar We have recently reproduced both the DHA deficit and vascular dysfunction in pregnant rats that affected their offspring. We conclude that diabetes induces a selective EFA deficiency in pregnancy. Male animals are known to be more susceptible to EFA deficiency, so the reduction in male offspring born to EFA-deficient mothers was explained as a higher prenatal male mortality.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google Scholar The intrauterine sex bias is seen in anthropometry at birth so gender sensitivity to EFA is not only apparent before sexual maturity but before birth. That it was intrauterine loss of males was established by the reduction in litter size without any change in the number of females born.2Rivers JPW Crawford MA Maternal nutrition and the sex ratio at birth.Nature. 1974; 252: 297-298Crossref PubMed Scopus (82) Google Scholar The similarity of our finding with that reported by Rajasanowski and co-workers of a loss of male offspring in diabetic pregnant women in whom a DHA deficit would be expected, is striking. The change in sex ratio in mice with EFA deficiency, experimental and then human evidence of a metabolic EFA deficiency in diabetes, evidence of diabetic vascular dysfunction followed by the change in sex ratio in the offspring of women with IDDM completes a circle of evidence that intrauterine lipid milieu affects the products of conception. This work is supported by the British Diabetic Association, the March of Dimes, Christopher H R Reeves Charitable Trust, and the Mother and Child Foundation. We thank B Thomas for her contribution." @default.
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• W4237788904 title "Sex ratio of offspring of diabetics" @default.
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