Endogamy may up infertility risk in Indian men

A team of researchers have identified that deletions of the Y chromosomes, responsible for production of sperms, can cause infertility in Indian men.

The study, illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.

According to the researchers, deletions in the AZoospermia Factor (AZF) regions on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility.

For the study, the researchers screened blood samples of 973 infertile men, consisting of 771 azoospermia (complete absence of sperm), 105 oligozoospermia (low sperm count) and 97 oligoteratozoospermia (low sperm count with abnormal shape and size) patients.

The deletion screening was carried out using AZF-specific markers.

The experiments were carried in accordance with the relevant guidelines and regulations approved for research on human samples.

The study revealed deletion events in a total of 29.4 per cent of infertile Indian men. Of these, non-allelic homologous recombination events accounted for 25.8 per cent.

Indian populations are unique in their origin and have been practicing endogamy for the last two thousand years, and therefore it is important to add a study of the frequencies of AZF deletions on the Y chromosome and their association with fertility in Indian idiopathic infertile men to similar studies from other parts of the world, the researchers said.

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Tiny cell: Good news for cancer survivors

A scientist at the National Institute for Research in Reproductive Health (NIRRH) in Mumbai – an institute under the Indian Council of Medical Research (ICMR) –n says a new type of stem cell identified by her team can help restore fertility in men and women who have undergone treatment for cancer.

Cancer treatment, or ‘oncotherapy’, that involves use of radiation and chemicals, renders patients infertile as an unwanted side effect and, while cured of cancer, they cannot beget children.

Though women are born with a lifetime reserve of ‘oocytes’ (immature eggs), these are wiped out by oncotherapy. In males, the testes responsible for the production of sperms stop making them following cancer treatment.

Currently accepted approaches for fertility preservation require male patients to deposit their sperm in ‘cryo-banks’ before beginning cancer treatment for later use. Similarly women, wanting to have children, must have their eggs or embryos ‘cryopreserved’ for use after oncotherapy.

“Such approaches are invasive, expensive, technically challenging and depend on assisted reproductive technologies,” reports a cell biologist.

According to the report, there is now a way out. She says research by her team over the years led to identification of a novel population of ‘Very Small Embryonic-Like stem cells (VSELs)’, in testis (in males) and ovaries (in females).

Being ‘quiescent’ by nature, these primitive stem cells (VSELs) survive cancer therapy and therefore can offer young cancer survivors options to have children without having to bank their sperms or embryos prior to oncotherapy, says the report.

“The VSELs have remained elusive over decades due to their small size and presence in very few numbers,” she says.

The discovery of these unique VSELs (in testes and ovaries) that do not succumb to oncotherapy “opens up an alternative strategy to regenerate non-functional gonads and ovaries in cancer survivors,” says the biologist.

While VSELs survive cancer treatment, their original “habitat” (or niche) however gets destroyed by oncotherapy. To make the VSELs functional, their “niche” should be re-created by transplanting “mesenchymal cells” – another type of stem cells taken from the bone marrow – into the testes, says the report.

A simple and direct transplantation of “mesenchymal cells in the non-functional gonads may suffice to regenerate them,” she says. “Similarly, transplantation of ‘ovarian surface epithelial cells’ may allow the VSELs to regenerate nonfunctional ovaries.”

“This approach to fertility restoration is safe,” says the biologist pointing out to earlier studies carried out in her laboratory in mice which had shown that this method restored the role of non-functional ovaries and resulted in the birth of fertile offsprings.

“Our group also successfully restored spermatogenesis (sperm production) in non-functional mouse testis by transplanting niche (mesenchymal) cells, into the testis,” she said.

In the light of these findings, she says the field of oncofertility may undergo a sea-change and existing strategies of cryopreservation of gametes and gonadal tissue for fertility preservation in cancer patients will have to be revised. “Pilot clinical studies (in humans) need to be undertaken.”

“VSELs may be an alternative cell source for induced Pluripotent Stem (iPS) cells,” said a researcher. “But it is still far away from the clinic as isolation and large scale expansion of these cells has to be standardized.” 

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