History And Features Of Polycystic Ovary Syndrome

Polycystic ovary (or ovarian) syndrome (PCOS) at the beginning was described in 1935. (Stein, and Leventhal., 1935). As far as the discovery of polycystic ovaries is concerned it was found at least a century before its description in 1935.( Vallisneri et al., 1721; Chereau 1844; Rokitanski 1855). It affects 6% to 8% of women around the globe, using the National Institutes of Health (NIH) 1990 criteria (Knochenhauer et al., 1998 ; Diamanti-Kandarakis et al., 1999 ; Michelmore et al., 1999; Asuncion et al., 2000; Aziz et al., 2004).

PCOs can be considered one of the most common disorders of humans, and the single most common endocrine abnormality of women of reproductive age. Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women that affects both reproductive and metabolic function (Franks 1995). Its diagnosis is based on the presence of at least two of the following criteria:

• Hyperandrogenism,which is determined by the presence of total testosterone (TT) or free testosterone (FT) excess or hirsutism.
• Ovarian dysfunction (OD), this is characterized by oligo-amenorrhea and chronic anovulation.
• The detection of a specific polycystic ovarian morphology (PCOm) (presence of cysts).

All disorders which are caused by the excess of androgen should be eliminated (Zawadski and Dunaif., 1992; Azziz et al., 2009). There is both scientific and clinical evidence that PCOS may be characterized by a list of dysmetabolic features, chiefly insulin resistance and compensatory hyperinsulinemia, glucose intolerance states, lipid abnormalities and low-grade inflammation (Conway et al., 2014). Excess body weight and obesity are associated with PCOS and this worsen the hormonal and metabolic features of PCOS and may, possibly, reduce the responsiveness to the most common therapeutic strategies extensively used around the globe.

The prevalence of polycystic ovaries in the general population appears to decrease with age, and was observed to be only 7.8% in women older than 35 years, compared with 21.6% in women younger than this age.( Koivunen et al., 1999). Hyperandrogenism can show itself in the form of unwanted hair growth or hirsutism, seborrhea, and/or acne, and androgenic alopecia or male pattern balding. The menstrual dysfunction of PCOS is generally characterized by rare or absent menstrual bleeding.

Alternatively, polymenorrhea is relatively rare, present in only 1.5% of untreated patients with PCOS ( Aziz etal 2004). Menstrual irregularity may start at menarche. Some patients may give a history of regular cycles for a short period of time following menarche, followed by the onset of oligomenorrhea. the prevalence of menstrual dysfunction in PCOS changes with age, decreasing as the patient approaches menopause (Elting etal 2000).

Three features are generally assessed to define polycystic ovaries, including:

• ovarian size and volume,
• stromal volume,
• follicle size and number.

Based on the available literature (Pache etal 1992; van Santbrink et al., 1997; Jonard et al., 2003) the Rotterdam criteria defines polycystic ovaries exclusively on total follicle number, defined as the presence of 12 or more follicles throughout the ovary measuring 2 to 9 mm in diameter. Obesity often accompanies PCOS and about 50% of women with this disorder are obese (Azziz et al., 2004). There is higher risk of hypertension, increase level of plasminogen inhibitor type 1, high concentration of endothelin, cardiovascular disease and abnormal function of endothelial in patients with this disorder (Dahlgren et al., 1992).

Insulin resistance is also responsible for reduction in the mitochondrial respiration (Petersen and Shulman, 2006). increased risk of metabolic aberrations, along with insulin resistance and hyperinsulinism, incudes type 2 diabetes mellitus, dyslipidemia, cardiovascular disease, and endometrial carcinoma (Azziz., 2003; Ovalle and Aziz., 2002). PCOS patients often produce oocytes of poor quality, leading to lower fertilization, (Sengok et al., 1997; Homburg, et al., 1993 ; Kodama et al., 1995; Macdougall et al., 1993; Dor et al., 1990) cleavage and implantation rate,( Cano et al., 1997) and higher miscarriage rate( Joham et al., 2014 ; Sahu et al., 2008). Elevated serum homocysteine (Hcy) levels are reported in PCOS patients( Yarali et al., 2001; Badawy et al., 2007; Schachter et al.,2003 ).

Moreover, abnormally high level of homocysteine (Hcy) is detected in the follicular fluid of polycystic ovaries (Berker et al., 2009). Mitochondria The mitochondrial (mt) genome (mtDNA) is a circular molecule containing 13 protein‐encoding genes that contribute proteins to complexes I, III, IV, and V of the oxidative phosphorylation system, as well as two rRNAs and 22 tRNAs [Anderson et al., 1981]. These RNAs are essential components for the translation and transcription of the 13 protein‐encoding genes and are complemented by a number of imported nuclear‐encoded factors such as the aminoacyl tRNA synthetases (aaRSs) [Tuppen et al., 2010a].

The rules governing mitochondrial genetics are distinct from those of nuclear genetics. These include maternal inheritance [Giles et al., 1980] and the presence of multiple copies of the mtDNA within each cell [Wallace, 1992]. Mitochondria play a central role in energy producing in the form of ATP through oxidative phosphorylation (OXPHOS) (Wallace and Chalkia, 2013). In addition to their role in energetic conversion, mitochondria participate in numerous other essential cell functions such as the regulation of apoptosis, calcium homeostasis, Fe–S protein synthesis, and pyrimidine and haem synthesis (Delbart, 2000). Alternations in mitochondrial function, dynamics and biogenesis are often associated with peripheral IR and glucose intolerance (Cheng et al., 2010 ; Sera et al., 2013).

Analysis of oxygen consumption in blood leukocytes has indicated that mitochondrial complex I respiration is reduced in women with PCOS compared with in age- and BMI-matched control subjects (Victor et Al., 2009). Similar to nuclear DNA, mtDNA is also subjected to epigenetic modifications that influence mitochondrial gene expression, biogenesis and function (Rebels et al., 2009; Metodiev, et al., 2009). Mt-tRNALeu(UUR) A3302G, mt-tRNAGln T4395C, mt-tRNASer(UCN) C7492T [13], mt-tRNAAspA7543G, mt-tRNALys A8343G, mt-tRNAArg T10454C and mt-tRNAGlu A14693G mutations occurred at evolutionarily conserved nucleotides of the corresponding tRNAs, thus suggesting mt-tRNA dysfunction may be involved in the pathogenesis of PCOS. However, the role of mitochondrial dysfunction in PCOS patients carrying these mt-tRNA mutations remained poorly understood.