Why does fertility drop after age 35? A molecular explanation

In this post my passion for biology will come out as a bit technical but I will try to simplify it as much as possible.

Although the quality of life has allowed us women to be splendid forty-year-olds (more or less) compared to a few decades ago, our ovaries have nevertheless maintained their biological age and therefore age the same. It annoys me to say it since I too am this age but… this is the reality of the facts.

One of the culprits is a gene, which is often in the headlines because its mutated version predisposes to breast cancer: the BRCA1 gene.

Its normal versions, on the other hand, are essential for the fertility of us women . The oocytes of young women, aged between 24 and 35 years, contain high levels of BRCA1 (in gray in the photo below) compared to the oocytes taken from older women (36-41 years), the OLDs you see in the photo .

A group of researchers funded by the American National Institutes of Health h have developed a new theory on why a woman’s fertility decreases after passing the age of 35 and at the same time suggest an approach that could help slow the aging process and improve e prolong fertility.

The interesting discovery is that   the more women age, the more the egg cells are enriched with errors and defects that lead to their death as the DNA repair systems are worn out and no longer work.

It is known that defects in the BRCA1 gene, involved in DNA repair mechanisms, are linked to the onset of breast cancer. Now the defects are also being linked to early menopause as well.

A woman’s ability to conceive and maintain a pregnancy is known to be linked to the number and health of her egg cells. At birth, a woman’s ovaries contain a “lifetime” supply of oocytes (known as primordial follicle oocytes). By age 40, the number of oocytes drops dramatically. By age 50, its initial supply of about 1 million cells drops to virtually zero. Only a small percentage of oocytes, around 500, are released via ovulation during a woman’s reproductive life. The remaining 99.9 percent is eliminated through the cell suicide mechanism (a normal process that prevents the spread or survival of damaged cells).

According to this study, older oocytes show this type of damage more frequently than younger ones. The researchers also found that older oocytes are less able to repair breaks in DNA due to fewer repair molecules.

Many of these studies stem from research on the BRCA1 gene that has been studied for over 20 years for the link of its modified versions with a high risk of breast cancer. Breeding mice lacking this gene, it was discovered that its healthy version is vital for reproductive health. Mice without the BRCA1 gene were less fertile, had fewer oocytes, and had more double-stranded DNA breaks in their remaining oocytes than normal mice.

Abnormal versions of BRCA1 appear to cause the same problems in humans. Studies by this research group suggest that if a woman’s oocytes contain mutant versions of BRCA1, her fertility will end much sooner than women who have normal versions of the gene.

All these results show how the ability of oocytes to repair double-stranded DNA breaks is closely connected with ovarian aging and, consequently, with a woman’s fertility. This understanding at the molecular level points to new reproductive therapies. In particular, the scientists suggest that if ways can be found to strengthen the DNA repair systems in the ovaries, it could lead to treatments that can improve or prolong fertility.

Kathryn Barlow is an OB/GYN doctor, which is the medical specialty that deals with the care of women's reproductive health, including pregnancy and childbirth.

Obstetricians provide care to women during pregnancy, labor, and delivery, while gynecologists focus on the health of the female reproductive system, including the ovaries, uterus, vagina, and breasts. OB/GYN doctors are trained to provide medical and surgical care for a wide range of conditions related to women's reproductive health.

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