Unlock Phase 1:-The question we can we unlock those genes of PCO?? : The unlock phase -1: Can we unlock the candidate genes resulting in to PCO and killing hundreds of women in India a daily due to DM, CVS (MI in particular), hemorrhagic stroke , Thrombotic stroke , endometrial Ca ?? PCOS is a multifactorial polygenic disease (interaction between several genetic and environmental factors), with a heritability of ~70 %. It is intrinsically difficult to study by a genetic point of view, and most of the current literature (>70 studies based on the candidate gene approach) is inconclusive, with many studies resulting inconsistent, controversial, and without a clear consensus. Recently, the inheritance was confirmed by some authors who found that PCOS was present in 35 % of the mothers and 40% of the sisters of PCOS patients. Moreover, increased incidence of insulin resistance in the fathers and brothers of PCOS women has been considered as the “male phenotype” in PCOS families. Ethnic variations of genetic expression for hyperandrogenism: à phenotypic variability of hyperandrogenic disorders. -The genes involved in the pathogenesis of hyperandrogenism are expressed in a variable way depending on the factors predominating in every different ethnic population. This explains the phenotypic variability of hyperandrogenic disorders. What is nongenetic inheritance?? Environmental cause of PCO?? .Some insults during pregnancy may induce to intrauterine growth retardation, which probably induces a “thrifty phenotype” in small for gestational age babies potentiated by in adult life by environmental factors such as a sedentary lifestyle and a diet rich in saturated fat. . To summarize there is one nongenetic theory of PCO which is of no less importance than genetic cause of PCO.:-theory is that the features of PCOS families result from nongenetic inheritance,and they are related to environmental factors that are present only in the affected families. Researchers have hypothesized that some insults during pregnancy may induce to intrauterine growth retardation, which probably induces a “thrifty phenotype” in small for gestational age babies.These have a high risk of suffering from insulin resistance, which may result in hypertension, glucose intolerance, adrenal axis hyperactivity with relative cortisol excess, functional hyperandrogenism, and PCOS later in life, especially if they are exposed to environmental factors such as a sedentary lifestyle and a diet rich in saturated fat. These environmental factors may cluster in certain families because exercising and dieting are greatly influenced by parental lifestyle. The metabolic abnormalities of the “thrifty phenotype” can induce additional insult to the pregnancies of these SGA (small for gestational age) and PCOS women, and these defects might be transmitted to another generation without the participation of any genetic abnormality. Q. Can we prevent nongenetic inheritance of PCO?? If small for gestational age babies , after birth and during upbringing have healthy habits, insulin resistance and its consequences might be improved, and theoretically, the third generation -à their fetuses will not be exposed to a hostile metabolic environment during pregnancy(as mother has god lifestyle during her childhood and puberty, adolescent and such good health habits continue to be practiced in childbearing age too then her siblings will not have PCO. This dedication of adhering to strict good eating and exercising habit will , prevent nongenetic inheritance of these conditions, PCO, DM, MI in particular . However, intrauterine growth restriction might be influenced by genetic variants as well, and the most likely scenario is represented by an interaction between predisposing genetic abnormalities and unfavorable environmental conditions. Thus, even if several studies conducted in families of women with PCOS have demonstrated the genetic basis of the syndrome, nowadays a genetic pattern certainly involved in PCOS predisposition has not been identified. Most studies have included different kinds of genes: those related to androgen biosynthesis and action and their regulation, genes involved in insulin resistance and associated disorders, and also genes involved in chronic inflammation and atherosclerosis UNLOCK Phase 1 : Genetic cause of PCO & Environmental cause of PCOS( a) unhealthy environment while foetus was inside the uterus and after child birth such intrauterine insult are aggravated by ( b )environmental factors such as a sedentary lifestyle and a diet rich in saturated fat.

Unlock Phase 1:-The question we can we unlock those genes of PCO?? : The unlock phase -1: Can we unlock the candidate genes resulting in to PCO and killing hundreds of women in India a daily due to DM, CVS (MI in particular), hemorrhagic stroke , Thrombotic stroke , endometrial Ca ?? PCOS is a multifactorial polygenic disease (interaction between several genetic and environmental factors), with a heritability of ~70 %. It is intrinsically difficult to study by a genetic point of view, and most of the current literature (>70 studies based on the candidate gene approach) is inconclusive, with many studies resulting inconsistent, controversial, and without a clear consensus. Recently, the inheritance was confirmed by some authors who found that PCOS was present in 35 % of the mothers and 40% of the sisters of PCOS patients. Moreover, increased incidence of insulin resistance in the fathers and brothers of PCOS women has been considered as the “male phenotype” in PCOS families.

Ethnic variations of genetic expression for hyperandrogenism: à phenotypic variability of hyperandrogenic disorders. -The genes involved in the pathogenesis of hyperandrogenism are expressed in a variable way depending on the factors predominating in every different ethnic population. This explains the phenotypic variability of hyperandrogenic disorders.

What is nongenetic inheritance?? Environmental cause of PCO?? .Some insults during pregnancy may induce to intrauterine growth retardation, which probably induces a “thrifty phenotype” in small for gestational age babies potentiated by in adult life by environmental factors such as a sedentary lifestyle and a diet rich in saturated fat. . To summarize there is one nongenetic theory of PCO which is of no less importance than genetic cause of PCO.:-theory is that the features of PCOS families result from nongenetic inheritance,and they are related to environmental factors that are present only in the affected families. Researchers have hypothesized that some insults during pregnancy may induce to intrauterine growth retardation, which probably induces a “thrifty phenotype” in small for gestational age babies.These have a high risk of suffering from insulin resistance, which may result in hypertension, glucose intolerance, adrenal axis hyperactivity with relative cortisol excess, functional hyperandrogenism, and PCOS later in life, especially if they are exposed to environmental factors such as a sedentary lifestyle and a diet rich in saturated fat. These environmental factors may cluster in certain families because exercising and dieting are greatly influenced by parental lifestyle. The metabolic abnormalities of the “thrifty phenotype” can induce additional insult to the pregnancies of these SGA (small for gestational age) and PCOS women, and these defects might be transmitted to another generation without the participation of any genetic abnormality.

Q. Can we prevent nongenetic inheritance of PCO?? If small for gestational age babies , after birth and during upbringing have healthy habits, insulin resistance and its consequences might be improved, and theoretically, the third generation -à their fetuses will not be exposed to a hostile metabolic environment during pregnancy(as mother has god lifestyle during her childhood and puberty, adolescent and such good health habits continue to be practiced in childbearing age too then her siblings will not have PCO. This dedication of adhering to strict good eating and exercising habit will , prevent nongenetic inheritance of these conditions, PCO, DM, MI in particular . However, intrauterine growth restriction might be influenced by genetic variants as well, and the most likely scenario is represented by an interaction between predisposing genetic abnormalities and unfavorable environmental conditions.

Thus, even if several studies conducted in families of women with PCOS have demonstrated the genetic basis of the syndrome, nowadays a genetic pattern certainly involved in PCOS predisposition has not been identified.

Most studies have included different kinds of genes: those related to androgen biosynthesis and action and their regulation, genes involved in insulin resistance and associated disorders, and also genes involved in chronic inflammation and atherosclerosis

UNLOCK  Phase 1 : Genetic cause of PCO & Environmental cause of PCOS( a) unhealthy environment while foetus   was inside the uterus  and after child birth such intrauterine insult are aggravated  by  ( b )environmental factors such as a sedentary lifestyle and a diet rich in saturated fat.