Ovarian aging in women correlates with the progressive loss of both the number and quality of oocytes. When these processes occur early or are accelerated, their clinical correlates are diminished ovarian reserve and/or premature ovarian insufficiency. Both these conditions have important consequences for the reproductive and general health of women, including infertility. Although there are many contributing factors, the molecular mechanisms underlying many of the processes associated with ovarian aging have not been fully elucidated. In this review, we highlight some of the most critical factors that impact oocyte quantity and quality with advancing age. We discuss chromosomal factors including cohesion deterioration and mis-segregation, errors in meiotic recombination, and decreased stringency of the spindle assembly checkpoint. DNA damage, telomere changes, reactive oxygen species and mitochondrial dysfunction as they relate to ovarian aging, and well-known gene mutations associated with primary ovarian insufficiency and diminished ovarian reserve are also discussed. Additionally, studies investigating recently acknowledged cytoplasmic factors associated with ovarian aging including protein metabolic dysregulation and microenvironmental alterations in the ovary are presented. We use both mouse and human studies to support the roles these factors play in physiologic and expedited ovarian aging, and we propose directions for future studies. A better understanding of the molecular basis of ovarian aging will ultimately lead to diagnostic and therapeutic advancements that would provide women with information to make earlier choices about their reproductive health.

As the ovary seems to be a favorable organ for the quantitative estimation of cell growth, we undertook to analyze the growth energy of the granulosa ceils in the ovaries of normal guinea pigs and also to study the growth energy of these cells under certain pathological conditions. Method.The growth energy was estimated by the determination of the percentage of mitoses in granulosa cells in the follicles of the ovaries of normal guinea pigs. A large number of cells was counted and the number of mitoses ascertained, thus making possible a comparison of the proliferative power of the various follicles by the relative percentage of mitoses.The follicles were classified according to size into three groups, large, medium, and small, whose average measurements were: large, 788 by 611 /2;medium, 506 by 450/2; small, 215 by 130/2. These measurements are from the inner border of the theca interna on one side to the same point on the other side; i.e., the space lined by the theca interna.One other type of follicle was studied in normal ovaries; viz., the mature type whose characteristics have been described in earlier papers by Loeb? These follicles are on an average somewhat larger than the ordinary large follicle. There is relatively much more 1

Since the discovery of normal human hemagglutinins by Ehrlich and the pointing out of their occurrence in groups by Landsteiner (1) with subsequent confirmation by Jansky (2), Moss (3) and many others, numerous workers have contributed to the more decisive identification of these groups. It has been shown by absorption as well as by specific agglutination (Hektoen (4), Koekert (5),) that four definite types of human blood can be identified. Although iso-hemagglutinins are found in most species of lower animals it seems that no definite grouping exists. Ottenberg and Friedman (6) claim to have obtained definite typing in rabbits and steers. Hektoen (7) studied the blood of not less than ten of each of the following species: rabbit, guinea pig, dog, horse and ox. He did not observe iso-hemagglutination in any of them. Fishbein (8) studied 60 hogs, 60 cattle, 40 sheep, 25 rabbits, 10 dogs, and 20 frogs.

We have found in the serum of normal untreated guinea pigs substances which in vitro are toxic for the spermatozoa of the same animals from which the serum was obtained as well as for other individuals of the same species, although no demonstrable injury to these cells is evident under normal conditions in the body. Hetero immune spermotoxins on the other hand are well known and have been studied by a number of investigators. Landsteiner (1) pointed out that if guinea pigs are immunized against ox spermatozoa their serum acquires the property of rapidly immobilizing them. Metchnikoff (2) confirmed this work. Moxter believed that spermotoxins were not specific. Errors in his work, however, were pointed out by Metchnikoff, who claimed specificity for these spermotoxins. Metalnikoff (3) further substantiated the specificity of spermotoxins. This author also called attention to the existence of natural spermotoxins in the serum of rabbits for the spermatozoa of guinea pigs.

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